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Abbatecola, Clement. "Behavioral and functional imaging analyses of face and voice integration in gender perception". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1289.
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Cette thèse décrit l'intégration multimodale voix-visage pour la perception du genre à l'aide de méthodes comportementales et d'imagerie cérébrale. Dans une première étude psychophysique, les observateurs ont départagé des paires de stimuli voix-visage selon le genre du visage, de la voix ou du stimulus (sans instruction particulière). Une seconde étude a reproduit ce paradigme en ajoutant du bruit visuel et/ou auditif. Conformément à nos résultats théoriques, tâche et bruit peuvent tous deux être modélisés comme des facteurs de pondération. Les deux effets pourraient refléter des changements similaires de hiérarchie fonctionnelle avec la communication par cohérence comme implémentation potentielle de ce mécanisme en termes de modulation sélective de l'information par synchronisation des rythmes d'oscillation neuronaux. Une asymétrie en faveur de la modalité auditive a été trouvée dans les deux études comportementales ainsi que deux interactions : un effet multiplicatif du genre significatif lorsqu'on juge le visage et le stimulus ; un effet de cohérence significatif lorsqu'on juge le visage ou la voix. Une troisième étude en IRMf s'est intéressée aux modulations de connectivité effective entre l'aire fusiforme du visage et l'aire temporale de la voix durant la présentation de stimuli voix-visage en prêtant attention au genre du visage, de la voix ou du stimulus. Une telle modulation a été trouvée dans les tâches du visage et du stimulus en réponse au genre, et dans les tâches du visage et du stimulus en réponse à l'incohérence, deux modulations indépendantes qui pourraient être supportées par l’architecture anatomique en double contre-courantThis thesis describes face-voice multimodal gender integration using complementary behavioral and brain imaging techniques. In a first psychophysical study, observers judged pairs of face-voice stimuli according to face, voice or stimulus (no specific instruction given) gender. A second study tested the bottom-up effect of adding visual and/or auditory noise in the same paradigm. Top-down task and bottom-up noise could both be modeled as weighting effects, as predicted by our theoretical results. Both effects might reflect similar shifts in functional hierarchy. Communication through coherence offers a potential explanation for the neural basis of such a mechanism in terms of selective modulation of segregated cortical streams by oscillatory rhythm synchronization. An asymmetry in favor of the auditory modality was found in both behavioral experiments as well as two interaction effects, first a multiplicative gender effect in the face and stimulus tasks, second an effect of gender coherence in the face and voice tasks. In a third experiment we used fMRI to investigate effective connectivity modulations between the Fusiform Face Area and Temporal Voice Area during the presentation of face-voice stimuli while attending to either face, voice or any gender information. We found a change in effective connectivity for stimulus and face tasks in response to gender information, and for face and voice tasks in response to gender incoherence. These two independent modulations could be supported by the anatomical dual counterstream architecture
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Bell, Joseph Sumner. "Non-Linear Stimulus Integration in Olfactory Computation". Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467331.
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All animals must use patterns of olfactory receptor neuron (ORN) activity to compute appropriate behavioral responses to odors, but the form of this computation is unknown. In both flies and mammals, each ORN expresses one type of odorant receptor that determines its odor response profile, and all ORNs expressing the same receptor project to the same compartment in the brain, or glomerulus. These glomeruli constitute parallel processing channels that relay olfactory information to other areas, and are often co-activated by odors. One popular hypothesis holds that activity in each glomerulus contributes to a central representation of valence, or pleasantness, by a fixed linear weight. Alternatively, non-linear interactions between specific glomeruli could confer increased selectivity or sensitivity for ethologically important odors. We investigate these alternative models by optogenetically activating olfactory glomeruli in freely walking Drosophila, and use video tracking to analyze the behavioral responses of thousands of individual flies. Flies respond to optogenetic fictive odors, but require wind to orient their walking responses. Some glomeruli produce robust attraction when activated individually. Combining stimulation of pairs of glomeruli produces unpredictable results: some pairs sum to produce attraction greater than that elicited by either component, but others produce the same behavior as the more attractive component alone. Surprisingly, we find no reliably repulsive glomeruli, but some potently reduce attraction in combinations. Based on which glomeruli summate, we develop a simple model that establishes a lower bound on the dimensionality of internal olfactory representations. Although we provide evidence that the brain combines signals from glomeruli using several pools with overlapping but distinct sets of inputs, detailed computational analysis of walking trajectories suggests that flies respond to these stimuli by graded recruitment of a single behavioral program.Medical Sciences
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Knutson, Keith. "Britain's functional approach to integration /". free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9988679.
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Chong, Man-Tze Mabel. "Development of sensorimotor integration and modulation in zebrafish". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18784.
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Neural control of behaviour during development is a complicated orchestration of gene expression, neuronal differentiation, axonal projection, modification of intrinsic membrane properties and connectivity of neural circuits. The studies in this thesis combined genetic, molecular, and physiological assays to investigate neuromodulation, reticulospinal contribution, and neurogenic programming of the limited behavioural repertoire of developing zebrafish. Maturation of early swimming, the change from infrequent episodes of swim bursts to a sustained “beat-and-glide” pattern, was mediated by serotonergic modulation of the spinal network. Serotonergic immunoreactivity was first detected in neurons located in the ventral spinal cord at 2 days post-fertilization (dpf). A second population of serotonergic neurons was detected in the hindbrain but these remained isolated from the spinal cord in the stages studied (2-4 dpf). Serotonergic modulation of the fictive swim pattern only occurred in 4 dpf larvae, the time when “beat-and-glide” swimming emerges, but not in younger larvae. Application of serotonin did not affect properties of activity (beat-and-glide) periods, but instead reduced the periods of inactivity between activity periods. Hindbrain reticulospinal (RS) neurons displayed four types of activity patterns during simultaneous spinal motoneuron recordings of fictive swimming activity in zebrafish larvae. RS neurons generated these activity patterns even in the absence of ascending spinal input during development. The spinal CPG network, however, failed to produce rhythmic oscillations in the presence of N-methly-d-aspartate when it developed without descending RS input, indicating that the latter are necessary for development of CPG activity. In addition to swimming, zebrafish larvae also produce startle responses in reaction to potential danger, a behaviour that is missing in hi472 mutant larvae. hi472 mutation disruptLe contrôle neuronal du comportement durant le développement dépend de l'intégration complexe de l'expression génétique, de la différentiation neuronale, de la projection axonale, de la modification des propriétés membranaires intrinsèques et de la connectivité des circuits neuronaux. Les études décrites dans cette thèse regroupent des approches génétiques, moléculaires et physiologiques afin d'examiner la neuromodulation, la contribution du système réticulospinal et la programmation neurogène afin d'étudier le répertoire limité des comportements du poisson zébré en voie de développement. Vers la quatrième journée du développement les larves changent leur comportement de natation, ils passent d'épisodes rares et de courte durée de natation en un patron maintenu de type nage-et-glisse, ou le poisson exécute quelques fortes contractions de la queue suive d'une période de glisse. Nous avons démontré cette maturation de la natation précoce, est due à la modulation sérotoninergique du réseau spinal. L'immunoréactivité sérotoninergique est détectée initialement chez une population de neurones situés dans la moelle épinière ventrale à 2 jours post-fertilisation (jpf). Une deuxième population de neurones sérotoninergiques a été détectée dans le tronc cérébral mais celle-ci ne projette pas d'axones vers la moelle épinière aux stades étudiés (2-4 jpf). La modulation sérotoninergique du patron de natation fictive se manifeste seulement chez des alevins de 4 jpf, au moment ou la natation nage-et-glisse se déploie, mais pas chez des alevins plus jeunes. Nous avons aussi démontré que l'application de sérotonine n'a aucun effet sur les propriétés des épisodes de nage active mais par contre, résulte en une réduction de la durée périodes d'inactivité entre les épisodes de nage-et glisse. Les neurones réticulospinaux (RS) du tronc cérébral manifestent quatre types de patron d'acti
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Tuason, Maria Clarita. "Functional analysis of Proteolipid Protein regulatory sequence". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101805.
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Myelin is an evolutionarily late acquisition of the vertebrate nervous system which speeds electrochemical signaling in mature nerve fibers by providing insulation in the form of a lipid-rich multilammelar sheath. Proteolipid Protein (PLP) is the most abundant protein in mature mammalian central nervous system myelin where it serves as a structural component in addition to other yet undefined roles. It is coordinately regulated at the transcriptional level with other myelin genes such as Myelin Basic Protein (MBP). The major components of MBP transcriptional regulation have been defined using a strategy of targeted transgenesis at the hypoxanthine phosphoribosyl transferase (HPRT) locus allowing quantitative and qualitative in vivo analysis of the transcriptional control exerted by conserved non-protein-coding sequences in transgenic mice. This study describes the localization and functional characterization of PLP conserved non-protein-coding sequences. Conservation was surveyed using alignments of genome sequences for a number of vertebrates ranging in their evolutionary distance from mouse. Aligned sequences were also scanned for clusters of conserved consensus binding sites for sox 10, krox20, gtx and betaHLH transcription factors, which play key roles in nervous system development. Dissection of conserved non-protein-coding sequence resulted in the production of a series of 10 reporter constructs addressing the search for PLP regulatory elements. This series includes highly conserved regions, some of which contain clusters of transcription factor consensus sites, as well as lesser conserved regions which were suggested to have regulatory activity in previous investigations. Notably, in vivo evidence of the importance of intron 1 for expression in the nervous system led to subsequent deletion-transfection analyses revealing a seemingly potent enhancer, the antisilencer/enhancer (ASE) within the intron, which is functionally validated in this study. Of this series, 8 of the selected regions have been amplified successfully and cloned into HPRT targeting constructs with a minimal lisp promoter and LacZ reporter. All 8 constructs have been transfected into ES cells. Homologous recombinants with the transgene docked at HPRT were selected, and chimeras have been analyzed for 3 of these constructs. To our surprise, neither a construct containing 2kb of 5' flanking sequence, nor a construct containing the highly conserved intron 3, were able to drive expression at the peak of myelination. A construct containing the ASE was unexpectedly shown to drive expression in cells scattered within the central grey matter of the spinal cord in a pattern intriguingly similar to that seen embryonically from migrating oligodendrocyte progenitors. The lack of expression of the first 2 constructs suggests that PLP regulatory elements may be interdependent, but we anticipate that delivery into germline followed by developmental and analysis of the full series of constructs will bring light to the emerging picture of partnerships between regulatory elements, and will also reveal the identity of the cells driving expression from the ASE. Understanding PLP transcriptional control may lead to therapeutic interventions as associated diseases result predominantly from imbalances in gene dosage leading to abnormal levels of PLP protein.
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Bélanger, Danny. "Heterologous functional interactions of P2X ATP receptors". Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81596.
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Part I. In this work we show that P2X3 currents are acutely modulated by the GPCRs mGluR5 and P2Y2, and by the neurotrophin TrkA receptor, expressed in nociceptors, in the recombinant Xenopus oocyte system. The intracellular C-terminal domain of P2X 3 plays an important role in its functional coupling to TrkA. Preliminary studies suggest a role for PKC in the P2X3-TrkA cross-talk, but other routes may also contribute. Part II. Neurogenic and pharmacological stimulation of vascular smooth muscle P2X1 elicits a contractile response that we found was potentiated by serotonin acting through 5HT2A. We also found in Xenopus oocytes that P2X 1 currents in the desensitized state are potentiated by M1 ACh receptors and by phorbol ester stimulation of PKC. Part III. We have shown in Boue-Grabot et al. (2003) that there was an intracellular negative cross-talk and physical interaction between P2X2 and 5HT3A receptors. We also found a functional interaction between P2X2 and GABAA alpha2beta 3 receptor subtypes in HEK293 mammalian cells and in Xenopus oocytes; and we confirmed the findings of Sokolova et al. , (2001) in primary cultures of DRG neurons. (Abstract shortened by UMI.)
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Wilson, Jennifer M. M. "Mechanisms of neuronal integration in adrenomedullary sympathetic preganglionic neurons". Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6334.
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Sympathetic preganglionic neurons innervating the adrenal medulla (AD-SPN) regulate the release of adrenal catecholamines into the bloodstream. This research was undertaken to investigate the intrinsic properties and synaptic pathways characteristic of AD-SPN in neonatal rat spinal cord slice preparation. The presence of Lucifer Yellow from the patch pipette and Rhodamine-Dextran-Lysine from the adrenal medulla in the same neuron post recording identified AD-SPN. Active intrinsic properties revealed and characterised include: a potassium-mediated transient outward rectification present in 96% of AD-SPN and separable into a short 4-aminopyridine- and a long barium-sensitive component; a potassium-mediated sustained outward rectification revealed in TTx, activated positive to -50mV and blocked with quinine. These conductances contribute to the repolarising phase of the action potential. 89% of AD-SPN possessed potassium-mediated anomalous inward rectification. All AD-SPN displayed a high voltage-activated calcium spike that prolongs the action potential. The addition of internal caesium (140mM) revealed a low threshold spike mediated by T-type calcium channels that serve to facilitate burst firing. 75% of AD-SPN exhibited evidence of electrotonic coupling, indicated by characteristic oscillations in membrane potential and confirmed with dual recordings from electrotonically coupled AD-SPN. Electrotonic coupling promoted synchronous activity. An enhanced afterhyperpolarising potential facilitated transient termination of action potential firing forming bursts of activity. A role for calcium in the regulation of neuronal activity via action on electrotonic coupling was suggested by caffeine (10mM) decreasing, BAPTA-AM (15muM) and calcium free aCSF increasing the junctional conductance. Electrical stimulation of the descending fibres in both the ipsi- and contralateral funiculi evoked fast EPSPs in all AD-SPN that were mediated by both NMDA and non-NMDA receptors. A subpopulation of AD-SPN received fast IPSPs mediated by GABA acting via GABAA receptors. A train of stimuli (4 x 10Hz) in ipsi- and contralateral funiculi also evoked a slow IPSP mediated by noradrenaline acting via alpha 2-adrenergic receptors to increase a potassium conductance. The results provide insight into central mechanisms that contribute to the regulation of adrenomedullary catecholamine secretion.
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Tahvildari, Babak. "Functional organization of the perirhinal-lateral entorhinal circuit". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103185.
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The perirhinal cortex (PRC) and the lateral entorhinal cortex (LEC) are essential components of the medial temporal lobe memory system, but the functional organization and interconnectivity of these structures is poorly defined. In this thesis, novel in-vitro and in-vivo approaches were developed to investigate the synaptic organization, intrinsic properties and cholinergic modulation of neurons in the PRC and LEC. In-vivo and in-vitro field potential profiles, combined with current-source density analysis and in-vitro intracellular recordings, demonstrated the existence of bi-directional excitatory synaptic interactions between the PRC and the LEC. Intracellular recordings and dye injection were also used to perform a morphological and electrophysiological characterization of principal neurons located in layers II and III of the LEC. These studies revealed that principal neurons in layer II of the LEC possess more heterogeneous morphological and electrophysiological properties than those in layer III. Moreover, layer III principal neurons display extensively arborized basal and apical dendrites that extend into layers I, II, III and V. This widespread arborization may allow these neurons to integrate neural signals destined for, and coming from, the hippocampus. We also discovered that muscarinic cholinergic receptor activation allows principal neurons in layer III of the LEC to generate persistent activity at a fixed frequency following an excitatory stimulus. This activity can be terminated by the application of another excitatory stimulus, allowing the cells to toggle between "On" and "Off" states. Finally, pharmacological and ionic substitution experiments in-vitro established that the "On" and "Off" states of these cells are respectively dependent on Ca 2+-dependent non-specific channels, and BK-type Ca2+-dependent K+ channels. These studies expand our understanding of the network and cellular mechanisms by which neurons in the PRC and LEC may contribute to long-term and short term memory.
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Bernier, Louis-Philippe. "Functional regulation of P2X receptor channels by phosphoinositides". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=110361.
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Long after its initial discovery as part of DNA and as the main source of energy in the cell, the nucleotide adenosine-5'-triphosphate (ATP) is now rightfully considered as an important extracellular signalling molecule. It is now known that purinergic transmission plays significant physiological roles, notably in neuro- and gliotransmission, in the modulation of the innate and adaptive immune response, in smooth muscle constriction and in regulating blood clotting. It is also actively involved in the generation and maintenance of various pathological states, including chronic neuropathic and inflammatory pain.How purinergic signalling can be implicated in such a diverse array of mechanisms via only one signalling molecule comes from the variety of receptors that are activated by ATP. Two major types of ATP-sensitive receptors exist: the P2X ionotropic receptor channels and the metabotropic P2Y receptors. The P2X family of ATP-gated ion channels is composed of seven subunits that assemble as trimers to form receptors with various functional and pharmacological profiles. Like all ion channels, the activity of P2X receptor channels is tightly regulated by orthosteric and allosteric regulation mechanisms. This thesis provides evidence of a novel type of post-translational regulation mechanism where the levels of intracellular phosphoinositides (PIPn) modulate the channel activity of P2X receptors. The first article included in my thesis focuses on the P2X1 subtype, which is mainly involved in smooth muscle constriction in blood vessels and vas deferens, as well as in the control of platelet aggregation and blood clotting. We demonstrate that the activity of the P2X1 receptor channel is positively regulated by membrane PI(4,5)P2 (PIP2). Depleting the intracellular levels of PIP2 decreased the ATP-activated current carried through the P2X1 channel and had an inhibitory effect on ATP-mediated mesenteric artery constriction, a P2X1-dependent process. Direct binding between the P2X1 cytosolic tail and PIP2 is shown to be necessary for the full expression of P2X1 activity.The next article in this thesis describes the PIPn-dependent regulation of the P2X4 receptor channel, which is highly involved in the generation of neuropathic and inflammatory pain through its expression in spinal cord microglia. Results obtained show that complete P2X4 function is dependent on the levels of PIP2 and PI(3,4,5)P3 (PIP3). Both species of phospholipids potentiate the P2X4-mediated ionic current and calcium entry by directly binding to the C-terminal domain of P2X4 subunits. Activation of co-expressed microglial metabotropic receptors can trigger changes in PIP2 or PIP3 levels, which could affect the contribution of P2X4 in pain-inducing mechanisms.In the third report, we investigate the molecular characteristics of the interaction between membrane PIPn and the various P2X receptors that were shown to be directly modulated by the phospholipids. By analyzing the functional and PIPn-binding effects of various mutations performed on the C-terminal domain of the PIPn-sensitive P2X1, P2X4 and P2X7 subtypes as well as on the PIPn-insensitive P2X5 subtype, we identify the PIPn-binding regulatory motif of P2X receptors. The last article included in this thesis examines the dynamic changes in channel permeability brought by sustained activation of the microglial P2X4 receptor. We show that upon sustained ATP application, P2X4 channels form large conductance pores allowing the flux of large organic molecules. The large pore formation of co-expressed microglial P2X7 receptors has been extensively studied; we show here that P2X4-mediated permeation is mechanistically distinct and, in contrast with P2X7, does not induce membrane blebbing or cell death. Furthermore, we demonstrate that membrane PIPn potentiate the formation of this high-conductance P2X4 pore, suggesting that this property can be regulated by metabotropic changes in PIPn levels.Longtemps après la découverte de sa présence dans l'ADN et de son rôle en tant que principale source d'énergie chimique dans la cellule, le nucléotide adenosine-5'-triphosphate (ATP) est maintenant considéré comme une importante molécule de signalisation extracellulaire. La transmission purinergique est activement impliquée dans plusieurs processus physiologiques, notamment dans la neuro- et glio-transmission, la modulation de la réponse immunitaire innée et adaptative, la constriction vasculaire et la coagulation sanguine. Elle participe aussi à la génération et au maintien de divers états pathologiques, tels la douleur chronique neuropathique et inflammatoire.La signalisation purinergique est impliquée dans des processus aussi diversifiés par l'entremise d'une seule molécule de signalisation grâce à une grande variété de récepteurs activés par l'ATP. Les deux principaux types de récepteurs sensibles à l'ATP sont les récepteurs ionotropiques P2X et les récepteurs métabotropiques P2Y. La famille P2X de canaux ioniques activés par l'ATP est composée de sept sous-unités qui s'assemblent comme trimères pour former des récepteurs possédant divers profils fonctionnels et pharmacologiques. Comme tous les canaux ioniques, l'activité des P2X est étroitement régulée par des mécanismes de régulation orthostériques et allostériques. Cette thèse démontre l'existence d'un nouveau type de mécanisme de régulation post-traductionnel, où les niveaux de phosphoinositides (PIPn) intracellulaires modulent l'activité de canal ionique des récepteurs P2X.Le premier article porte sur le sous-type P2X1, qui contribue à la contraction des muscles lisses dans les vaisseaux sanguins et le canal déférent, ainsi qu'à l'agrégation plaquettaire. Nous démontrons que l'activité du récepteur canal P2X1 est positivement régulée par les PI(4,5)P2 (PIP2) membranaires. La déplétion des niveaux intracellulaires de PIP2 diminue l'amplitude du courant ionique induit par P2X1. Nous montrons que le couplage direct entre le domaine C-terminal cytosolique de P2X1 et PIP2 est nécéssaire pour l'expression complète de l'activité de P2X1.Le second article de cette thèse décrit la régulation PIPn-dépendante du récepteur canal P2X4, qui joue un rôle majeur dans la génération et le maintien de la douleur neuropathique et inflammatoire par son expression dans les microglies de la moelle épinière. Nous démontrons que le fonctionnement de P2X4 dépend des niveaux de PIP2 et de PI(3,4,5)P3 (PIP3). Les deux types de phospholipides potentialisent le courant ionique ainsi que l'entrée de calcium par le canal P2X4 en se liant directement au domaine C-terminal des sous-unités P2X4. Dans le troisième rapport, nous étudions les caractéristiques moléculaires de l'interaction entre les PIPn membranaires et les récepteurs P2X directement modulés par ces phospholipides. En analysant les effets fonctionnels de diverses mutations effectuées sur le domaine C-terminal des sous-types PIPn-dépendant P2X1, P2X4 et P2X7 et sur le sous-type PIPn-indépendant P2X5, nous identifions le motif nécessaire à la liaison P2X-PIPn et à la régulation fonctionnelle du canal par les PIPn.Le dernier article de cette thèse examine les changements dynamiques de la perméabilité du canal ionique apportés par une activation soutenue des récepteurs microgliaux P2X4. Nous montrons que, lors d'une application soutenue d'ATP, les canaux P2X4 forment des pores à haute conductance permettant le flux de molécules organiques à haut poids moléculaire. La formation de larges pores par les récepteurs P2X7 a été étudiée intensivement; nous démontrons ici que la perméation induite par P2X4 est mécanistiquement distincte et, à l'opposé de P2X7, ne mène à aucun réarrangement de la structure membranaire ni à la mort cellulaire. Les PIPn membranaires potentialisent la formation de ces pores à haute conductance par P2X4, suggérant que cette propriété peut être régulée par des changements intracellulaires des niveaux de PIPn.
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Foster, Nicholas Elgin. "Structural and functional correlates of mental musical transformation". Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96781.
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Music represents both a ubiquitous element in human cultures and a highly complex discipline to which some individuals devote decades of practice. Music is therefore an ideal medium with which to probe human auditory perception over a wide range of skill. Differences in brain structure and function have been reported in musicians (vs. untrained individuals), but because of methodological limitations, the links bringing together behavior, structure and function have remained indirect. This thesis consists of three neuroimaging studies that, together, elucidate some of the functional and anatomical substrates of aspects of melodic perception. Study 1 used functional magnetic resonance imaging (fMRI) and a mental pitch transposition task to localize cortical activity related to mental manipulation of melodic sequences; the results showed that recruitment of the intraparietal sulcus (IPS) is specifically related to successful mental transposition. Study 2 employed fMRI to test two follow-up questions: whether the same subregion of IPS is also involved in temporal manipulation of melodies, and whether transposition to more distant keys evokes greater activation in IPS. The results showed that in individual subjects, a common area of IPS subserves mental melodic transformations in both pitch-based and time-based reference frames, and that the magnitude of IPS activation is associated with the magnitude of the transformation required. Study 3 tested for anatomical correlates of mental pitch transposition ability, and found that both gray matter concentration and thickness in auditory cortex and IPS predict performance on this task. The structural effects in IPS were in close spatial correspondence with the functional effects in Studies 1 and 2. Although structural and functional effects showed positive correlations with musical experience, there was also evidence for a training-independent correlation between mental transposition ability and IPS structure/function, supporting the idea that pre-existing behaviorally relevant variation is further modified by training. These studies therefore provide convergent structural and functional evidence of a specific role for the IPS in a complex aspect of musical perception. The results are in agreement with models of dorsal sensory processing that emphasize abstract non-spatial computations, and advance the idea that posterior parietal cortex is important for systematic musical transformations.La musique représente à la fois un élément omniprésent dans la culture humaine et une discipline très complexe dans laquelle certaines personnes consacrent des décennies de pratique. La musique est ainsi un moyen idéal pour sonder la perception auditive humaine sur un large éventail de compétences. Les différences dans la structure et la fonction du cerveau ont été rapportées chez des musiciens (vs. individus non entraînés), mais en raison de limites méthodologiques, les liens réunissant les comportements, la structure et la fonction sont restés indirects. Cette thèse consiste en trois études en neuroimagerie qui ensemble, élucident quelques substrats anatomiques et fonctionnels des aspects de la perception mélodique. L'étude 1 utilise l'imagerie par résonance magnétique fonctionnelle (IRMf) et une tâche de transposition mentale de la hauteur des notes pour localiser l'activité corticale liée à la manipulation mentale de séquences mélodiques; les résultats ont montré que le recrutement du sulcus intrapariétal (SIP) est relié spécifiquement à la réussite d'une transposition mentale. L'étude 2 a utilisé l'IRMf pour répondre aux deux questions suivantes, à savoir si la même sous-région du SIP est également impliquée dans la manipulation temporelle des mélodies, et si la transposition de notes plus distantes évoque une plus grande activation dans le SIP. Les résultats ont montré que chez des sujets individuels, une aire commune dans le SIP favorise les transformations mélodiques mentales à la fois basées sur la hauteur des notes et sur des cadres de référence basés sur le temps, et que la magnitude de l'activation dans le SIP est associée avec la magnitude des transformations requises. L'étude 3 a testé les corrélats anatomiques de la capacité de transposition mentale de la hauteur des notes, et a montré qu'à la fois la concentration de matière grise et l'épaisseur dans le cortex auditif et dans le SIP prédit la performance à la tâche. Les effets structuraux dans le SIP étaient en étroite correspondance spatiale avec les effets fonctionnels dans les études 1 et 2. Bien que les effets anatomiques et fonctionnels aient montré des corrélations positives avec l'expérience musicale, il y avait aussi la preuve d'une corrélation entre la capacité de transposition mentale et la structure/fonction dans le SIP, indépendante de l'entraînement, appuyant l'idée qu'une variation comportementale préexistante est en outre modifiée par l'entraînement. Ces études sont par conséquent des preuves structurelles et fonctionnelles convergentes pour un rôle spécifique du SIP dans un aspect complexe de la perception musicale. Les résultats sont en accord avec les modèles du traitement sensoriel dorsal qui mettent l'accent sur des traitements non-spatiaux abstraits, et renforcent l'idée que le cortex pariétal postérieur est important pour des transformations musicales systématiques.
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Emanuel, Alan. "Signal Integration and Diversification by Melanopsin-Expressing Retinal Ganglion Cells". Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:33493393.
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There are three classes of light-sensing cells in the mammalian retina: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). This dissertation focuses on the signals generated by the ipRGCs, which are important for the regulation of many non-image-forming visual functions such as regulation of the circadian clock, pupillary light reflex, sleep, locomotor activity, and hormone levels. Dysregulation of these functions can have profound effects on health. How ipRGCs regulate these functions remains incompletely understood because many of their basic properties have not yet been established. To better understand ipRGCs, I conducted a quantitative electrophysiological examination of their light responses within the in vitro mouse retina.
Chapter 2 presents evidence that melanopsin, the light-sensing pigment that initiates phototransduction within ipRGCs, has three stable states that are interconverted by light. Two of these states are silent and have distinct spectral sensitivities, which allows ipRGCs to integrate over a relatively broad range of wavelengths. The stability of the active state results in the production of a persistent response that long outlasts the offset of the stimulus and allows ipRGCs to integrate light over time. Most light stimuli, including short-wavelength and white light produce a large fraction of the active state and its associated persistent response. In contrast, long-wavelength light produces a much smaller fraction of the active state and can be used to decrease the persistent response. The effects of melanopsin tristability appear to be particularly suited for the functions regulated by ipRGCs. These effects are absent in other known photoreceptors, which have pigments with only one or two stable states.
IpRGC phototransduction persists for minutes even after illumination has ceased because the signaling state of melanopsin is thermally stable. In Chapter 3, I describe experiments that examine how this persistence influences two fundamental aspects of ipRGC function: activation and adaptation. I found that increased persistence is associated with ipRGC activation that encodes a narrower band of light intensities. Thus, although persistence endows ipRGCs with temporal integration, it does so at the cost of dynamic range. In addition, persistence drives adaptation to desensitize the cell. Accordingly, acutely decreasing the persistent response with long-wavelength light can result in a subsequent recovery of sensitivity. However, this effect is highly variable across the population; some cells show greater desensitization from the long-wavelength light than resensitization from its reduction of the persistent response. Therefore, the balance of activation and adaptation differs among ipRGCs, such that light history may diversify the signals generated by the population.
There are multiple subtypes of ipRGCs, but even a single subtype regulates many distinct functions. In Chapter 4, I describe a systematic approach for examination of the diversity in the biophysical parameters governing ipRGC signaling, including phototransduction, synaptic input, passive membrane properties, and spike generation. Comparison of these parameters across cells revealed a large degree of heterogeneity both between and within two morphologically-defined ipRGC subtypes. The diversity in ipRGC signal generation does not appear to divide among ipRGCs that project to different brain regions that control distinct functions; ipRGCs that project to the hypothalamus have diverse physiological properties that are highly overlapping with the ipRGCs that project to the pretectum. This suggests that functions driven by both areas have access to information from ipRGCs with a similar, broad range of characteristics.
In summary, the research described within this dissertation has revealed that visual pigments can be tristable in physiological conditions and this tristability has unique consequences for signal generation. Furthermore, it has provided insight into the high degree of biophysical diversity that can be present even within a single, molecularly-defined type of neuron. These findings contribute to the emerging understanding of ipRGCs and their distinctions from the classical rod and cone photoreceptors.Medical Sciences
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Stacey, Stephanie. "Notch signaling promotes functional diversity among Drosophila Longitudinal Glia". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86934.
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Reciprocal interactions between neurons and glia are essential for the development and maintenance of neural circuits. The many functions of glial cells and the intrinsic and extrinsic factors that regulate their diversity and functional specification are not well understood. An important challenge is to understand how neurons contribute to glial subtype differentiation and how glial subtypes serve neuronal function. My thesis work has identified a number of Drosophila glial subtype specific genes whose expression is regulated by neuron glial interactions through the Notch (N) signaling pathway. I found that N signaling positively regulated the expression of two subtype specific genes and negatively regulated the expression of four subtype specific genes. Additionally, the expression of these six genes was dependent upon the glycosyltransferase Fringe (Fng) which sensitizes the N receptor to activation by its ligand Delta (Dl). I determined that the subtype specific glial glutamate transporter, Excitatory amino acid transporter 1 (Eaat1), was expressed in an anterior subtype of the longitudinal glia (LG). Through the generation of Eaat1 mutants, I found that the LG were important for larval locomotion. My data supports an acute role for Eaat1 during larval locomotion rather than a developmental requirement. Dorsal motor neuron output was impaired in Eaat1 mutants suggesting that the anterior LG regulate CNS glutamatergic transmission important for dorsal motor neuron function. My work describes functional diversity among subtypes of glia whose differentiation is influenced by neuron-glial communication via Dl-N signaling.Les interactions réciproques entre neurones et cellules gliales sont essentielles pour le développement et l'entretien des circuits neuronaux. Les nombreuses fonctions des cellules gliales ainsi que les facteurs intrinsèques et extrinsèques qui régissent leurs diversités et spécifications fonctionnelles ne sont pas bien compris. Un défi important est de comprendre comment les neurones contribuent à la différenciation des sous-types gliaux et comment ces sous-types servent la fonction neuronale. Mon travail de thèse a identifié un certain nombre de gènes spécifique à certains sous-types gliaux chez la Drosophile dont l'expression est régulée par des interactions neurones gliales à travers la voie de signalisation Notch (N). Mes travaux m'ont permis d'identifier six gènes exprimés de façon spécifique dans certains sous-types gliaux et dont l'expression est régulé par la voie de signalisation N. Notamment l'expression de ces six gènes dépend de la glycoslytransferase Fringe (Fng), qui sensibilise les récepteurs N à l'activation par son ligand Delta (Dl). J'ai observe que Eaat1, un transporteur du glutamate, était seulement exprime dans les cellules gliales longitudinales antérieures (LG). Grâce à la génération de mutants Eaat1, j'ai trouvé que les cellules LG sont importantes pour la locomotion larvaire. Mes données favorise un rôle aigu pour Eaat1 pour la locomotion larvaire plutôt qu'une exigence lors du développement. Chez les mutants Eaat1 l'activité des neurones moteurs est altérée suggérant que les LG antérieure régulent les transmissions glutamatergique du système nerveux central importante pour la fonction des neurones moteur dorsale. Mon travail décrit la diversité fonctionnelle des sous-types gliaux dont la différenciation est influencée via des interactions neurones gliales grâce à la voie de signalisationjDl-N.
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Simoneau, Steve. "Functional interactions between the p75 neurotrophin receptor and TrkA". Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=30747.
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The p75NTR neurotrophin receptor has previously been shown to increase the responsiveness of TrkA to NGF, the preferred ligand of TrkA. We performed structure/function studies to determine the domains of p75 NTR involved in this functional interaction. Co-expression of p75NTR in 293T cells enhances NGF-mediated TrkA autophosphorylation while the intracellular domain of p75NTR is not required for this function. Indirect evidence has previously suggested that p75 NTR may also play a role in reducing non-preferred ligand activation of TrkA. We tested this directly and found that p75NTR reduces both basal and NT-3/NT-4-mediated TrkA autophosphorylation. In addition, we show that the intracellular domain of p75NTR can by itself reduce basal TrkA activity, suggesting the involvement of intracellular signaling. These data imply that the p75NTR receptor can functionally interact with the TrkA receptor through two distinct domains. We hypothesize that these interactions function in combination to help the TrkA receptor discriminate between preferred and non-preferred ligands, therefore increasing the specificity of activation of the TrkA receptor.
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Hildebrand, David Grant Colburn. "Whole-brain functional and structural examination in larval zebrafish". Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467176.
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Comprehending how neuronal networks compute is a central goal in neuroscience, but it is challenging to directly measure how information flows through and is processed by large circuits of interconnected neurons. Ideally, one would capture what every neuron represents and determine which of its counterparts this information was shared with. However, measuring neuronal activity requires high temporal resolution and finding the connections between neurons requires high spatial resolution. The constraints imposed by current techniques for evaluating neuronal population activity and network anatomy put these requirements at odds: those that sample rapidly typically do so with lower spatial resolution, while those that provide high spatial resolution generally sample slowly. Finding ways to combine the strengths of different approaches and applying them to relatively small nervous systems holds great potential for examining neuronal network function.
The translucence, genetic toolset, and small size of the larval zebrafish model organism make it ideal for whole-brain activity mapping at cellular resolution while presenting sensory stimuli and recording behavior. Constant improvements to reporters of neuronal activity and light microscope designs are being made to capture snapshots of neuronal activity more rapidly. However, existing methods for identifying neuronal connectivity in larval zebrafish are applicable to only a small fraction of the population at once. An efficient way to determine the neuronal network anatomy—or wiring diagram—of a circuit is to reconstruct connections from micrographs of continuous series of thin sections acquired with electron microscopy, but this technique has yet to be applied to studying neuronal circuits in larval zebrafish. Furthermore, its use has not yet approached the scale of the complete larval zebrafish brain.
This dissertation describes new tools for enhancing larval zebrafish activity mapping endeavors and the development of a serial-section electron microscopy approach to accomplish dense structural imaging of the complete brain. Together, these developments provide a foundation for studying neuronal network computation in the context of a behaving animal.Medical Sciences
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Zou, Hanzheng. "Python Integration with a Functional DBMS". Thesis, Uppsala University, Department of Information Technology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-112033.
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Python is an Object Oriented programming language and widely used nowadays. This report describes how to extend a functional database system Amos II for integration with Python. Several possibilities are analyzed to combine the Amos II C external interfaces with those of Python. Based on these discussions, new functionality has been added to the Python language by implementing a Python C external module. A basic API called PyAmos, interfacing Python and Amos II, is proposed and implemented in this work. To utilize object oriented nature of Python, some new Python classes are also defined for Amos II database access. The performance of PyAmos interface is also evaluated. This work shows how Python can be integrated with a functional DBMS.
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Goparaju, Balaji. "High level motion: neural correlates and functional connectivity". Thesis, Boston University, 2012. https://hdl.handle.net/2144/21157.
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Thesis (M.Sc.Eng.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.This thesis uses functional magnetic resonance imaging (fMRI) data to investigate: 1. The neural substrate of high level visual motion 2. The functional connectivity between a behavioral task and resting state. In chapter 1, we find the neural substrate of a set of psychophysical high level motion tasks. Specifically, we used tasks of visually guided navigation, such as heading from optic flow, landmarks, motion parallax, and collision detection. We also used tasks underlying the ability to perform object recognition from motion cues alone such as 3D Structure From Motion (SFM) and Biological Motion (BM). fMRI data was analyzed with Brain Voyager and activated anatomical areas were delineated using Matlab scripts developed in the laboratory. Several regions within the dorsal visual system elicited significant BOLD activity: the dorsal-occipital (BA19) and parietal lobes (BA 37, 40, 7). The ventral areas (BA 20, 21, 22, 38) showed significant BOLD activity only in BM and SFM and in heading tests using landmarks or motion parallax. We generated a schematic map with the overlapping areas among high level motion tasks, which can aid in diagnosis and rehabilitation of motion deficits in neurological patients. In chapter 2, we computed the functional brain connectivity between the brain areas in a resting state (subject performs no task), and during task (subject performs a visual motion task). In the resting state, we found connectivity using correlations between the posterior cingulate cortex (PCC), precuneus, medial prefrontal cortex (MPFC), lateral parietal cortex, and the hippocampal formation, which have been reported as the default mode network (DMN) since it represents correlated neural activity during a state of rest. We used bivariate correlations to compute functional connectivity using the CONN fMRI toolbox and in-house Matlab scripts. We computed a whole-brain analysis and compared network statistics in both, resting state and during task to investigate measures of integration such as path length and global efficiency, regional measures such as degree (number of connections) and betweenness centrality (number of shortest paths), and global measures such as small-worldness. The DMN and graph theoretical measures connectivity during task was stronger as compared with the resting state. We also computed these measures in task using a similar frequency spectrum as rest (0.009 Hz < f < 0.08 Hz), and in the full frequency spectrum. We find that on the whole, the connectivity measures in the DMN and the graph theoretical measure are stronger in the fullband signal processing analysis as compared to the bandpass version of the analysis.
2031-01-01
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Pribiag, Horia. "Spatiotemporal expression and functional role of TES Kinase in neurons". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86935.
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TES Kinases (TESKs) regulate actin dynamics via phosphorylation of cofilin, and can also regulate signaling pathways independently of kinase activity. Both isoforms are expressed in the brain, however their expression patterns and functional roles in the CNS have not been described to date. In this thesis we describe (1) the expression pattern of TESKs in the adult and developing mouse CNS, and (2) the role of TESKs in cytoskeletal rearrangements and neurite outgrowth in neuroblastoma cells and neurons. We observed regionally-restricted expression of both isoforms in the developing and adult CNS. Overexpression of either isoform caused a significant accumulation of F-actin in neuroblastoma cells and significantly inhibited neurite outgrowth of primary neurons. Expression of kinase-inactive TESKs did not affect basal F-actin or neurite outgrowth. siRNA knock-down of TESK1 caused a significant increase in neurite outgrowth in N1E-115 neuroblastoma cells, suggesting a role for TESKs in neurite outgrowth that is independent of kinase activity.Les Kinases TES (TESKs) règlent la dynamique de l'actine par la phosphorylation de cofilin, et peuvent aussi règler des voies de signalisation indépendamment de leurs activités de kinase. Les deux isoformes sont exprimés en cerveau, mais leurs modèles d'expression et rôles fonctionnels dans le système nerveux central (SNC) n'ont pas été décrits. Dans cette thèse nous décrivons (1) le modèle d'expression des TESKs dans le SNC de la souris adulte et en développement, et (2) le rôle des TESKs dans le réarrangement cytosquelettiques et le poussement des neurites dans des cellules neuroblastomes et des neurones. Nous avons observé une expression régionale pour les deux isoformes dans le SNC adulte et en développement. La supra-expression de l'une ou l'autre isoforme a causé une accumulation significative de F-actine en cellules neuroblastomes et a empêché de manière significative le poussement des neurites dans des neurones primaires. L'expression des TESKs inactifs n'a pas affecté le F-actin ou le poussement des neurites. L'abattrement de TESK1 avec siRNA a causé une augmentation significative dans le poussement des neurites en cellules neuroblastomes N1E-115, suggérant un rôle pour les TESKs dans le poussement des neurites qui est indépendant de l'activité kinase.
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Lê, Khanh-Tuoc. "Functional and biochemical characterization of central ATP-gated P2x channels". Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36032.
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Fast purinergic neurotransmission has recently been shown to be mediated through ionotropic P2X receptors activated by extracellular adenosine 5'-triphosphate (ATP). P2X protein mapping within central nervous system (CNS), P2X channel subunit composition pertaining to relevant native receptor phenotypes, and species-specific differences between mammalian P2X orthologs remain to be investigated.The first manuscript (Le et al., 1998a) reported the regional, cellular, and subcellular localization of P2X4 gene product within adult rat brain and spinal cord structures. P2X4 receptors were shown to be widely expressed on the postsynaptic side throughout the CNS.
The second manuscript (Le et al., 1998b) documented a novel P2X receptor phenotype resulting from the heteropolymerization between major central P2X4 and P2X6 subunits. P2X 4+6 heteromultimeric channel phenotypes were characterized by distinct time-dependent protein expression levels and novel pharmacological profiles compared to P2X4 homo-oligomers.
The third manuscript (Le et al., 1999) was undertaken based upon similar reasoning as well as experimental strategies as the P2X 4+6 study (Le et al., 1998b). The existence of heteromultimeric P2X1+5 receptors were screened with functional as well as biochemical assays demonstrating that this oligomeric complex gave rise to hybrid properties between homopolymeric P2X1 and P2X 5 subunits. Reciprocal co-purifications between interacting P2X 1 and P2X5 subunits were also demonstrated in this study.
The fourth manuscript (Le et al., 1997) reported the molecular cloning of the human ortholog (hP2X5R) of rP2X 5 subunit, which is being the most rare transcript among all reported rat P2X cDNAs to date. hP2X5R subunit was found to be a 422 amino acid-long protein and having 62% homology to rP2X5 receptors.
In an effort to contribute to a better assessment of the physiological roles of fast purinergic synaptic signaling (Le et al., 1998a) mediated likely by native receptors generated by heteromultimerization (Le et al., 1998b; Le et al., 1999) while keeping in mind that species-dependent differences between mammalian P2X orthologs (Le et al., 1997) should be taken into account whenever rodent systems would be used for drug screening studies. (Abstract shortened by UMI.)
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Klink, Ruby. "Functional organization and neuromodulation of entorhinal cortex layer II neurons". Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=42069.
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Morphological and electrophysical properties of layer II neurons from the medial entorhinal cortex were investigated in a rat brain slice preparation to enhance our understanding of the role the entorhinal cortex plays in the gating of afferent stimuli to the hippocampal formation.Morphological characterization revealed that layer II projection neurons fell into two distinct categories. 65% of neurons were identified as the stellate cells described previously. The remaining 35% had, for the most, a pyramidal-like morphology, and were referred to as non-stellates.
Electrophysiological characterization revealed that stellates and non-stellates had distinct electroresponsive properties. Notably, stellates, upon d.c. depolarization, generated subthreshold, sinusoidal-like, membrane potential oscillations at a mean frequency of 8.6 Hz and a 1-3 Hz repetitive bursting pattern, referred to as clustering. Non-stellates, when d.c. depolarized, never generated subthreshold oscillations nor spike clusters; instead they readily went into tonic firing.
Investigation of the main ionic mechanisms endowing stellates and non-stellates with their differential electroresponsiveness revealed that stellates exclusively possessed a fast, low threshold, Ba$ sp{2+}$-sensitive outward rectifier, which, in interplay with the persistent Na$ sp+$ conductance, generated the membrane potential oscillations.
The cholinergic agonist carbachol caused a depolarization in both stellates and non-stellates, associated with no change or a slight increase in apparent input resistance. In stellates, carbachol caused a decrease in the dominant frequency of the subthreshold membrane potential oscillations from 9.2 to 6.3 Hz. In non-stellates, carbachol transformed tonic firing into a slow voltage-dependent bursting discharge.
Investigation of the ionic mechanisms of the carbachol-induced depolarization in stellates and non-stellates revealed that it resulted mainly from activation of a Ca$ sp{2+}$ dependent cationic conductance largely carried by Na$ sp+$, mediated predominantly through m1 muscarinic receptor subtype activation.
Serotonin, in stellates, caused a variable response consisting of a hyperpolarization and/or depolarization, associated with a decrease in apparent input resistance, while in non-stellates, only the hyperpolarizing response was observed. In stellates, serotonin increased the frequency of subthreshold oscillations from 8.5 to 14.0 Hz. In non-stellates, serotonin did not affect spike-train adaptation nor the slow afterhyperpolarization following the train of spikes while it reduced both in stellates.
These results attest to the presence, in layer II of the medial entorhinal cortex, of two parallel information processing channels, both projecting to the hippocampal formation, and differentially modulated by the cholinergic and serotoninergic systems. One of these, the stellate channel, is endowed with robust rhythmic properties whose fundamental frequency can vary widely, depending on the relative tone of these two major neurotransmitter systems.
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Whatley, Benjamin. "Neurophysiological abnormalities in multiple sclerosis: Disease process or functional compensation?" Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117046.
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Background: Intracortical inhibition is reduced in patients with multiple sclerosis. The cause and implications of this change are unknown: it may result from damage within inhibitory systems or, alternatively, may represent compensatory downregulation of cortical inhibition.Objective: To examine the association between measures of intracortical inhibition and motor and cognitive abilities in patients with multiple sclerosis.Methods: 36 patients with the relapsing-remitting form of multiple sclerosis were recruited from a specialty clinic and underwent evaluation of motor and cognitive ability using the Multiple Sclerosis Functional Composite scale. Cortical silent period (cSP) and short-interval intracortical inhibition (sICI) were measured in both hemispheres using transcranial magnetic stimulation. 13 healthy controls were evaluated on the same measures. We calculated correlations between functional and neurophysiological outcomes, and evaluated hemispheric asymmetries.Results: Patients with remitting MS have significantly longer cSP durations (101.6±29.2msec) than healthy controls (82.2±22.4ms, t(47)=-2.166, p=0.035), indicating increased intracortical inhibition. Greater inhibition is associated with worse hand function as measured by the nine-hole peg test (dominant hand: ρ=0.360, p=0.031; non-dominant hand: ρ=0.351, p=0.039). Overall, cSP duration is comparable between cerebral hemispheres within the patient group (t(69)=0.633, p=0.529). However, among patients with significant hemispheric asymmetry for cSP duration, the direction of this asymmetry predicts asymmetry for hand function (ρ=0.950, p<0.001). Conclusion: These results support the hypothesis that alterations in cortical excitability in patients with MS reflect damage to inhibitory systems. In the context of earlier findings, our results also indicate that cortical excitability may change with respect to disease stage, and that the mechanisms underlying these changes may differ depending on stage. We cannot rule out the possibility that decreases in cortical excitability during the relapsing phase or in other subtypes of MS may be compensatory. Taking into account neurophysiological markers such as cSP may be useful in predicting disease severity.Historique: Les mesures d'inhibition intracorticale sont réduites chez les patients atteints de sclérose en plaques. La cause et les implications de ces changements sont inconnues : cela peut résulter d'un dommage dans les systèmes d'inhibition ou, alternativement, peut représenter des régulations descendantes compensatoires de l'inhibition corticale.Objectif: Pour examiner l'association entre les mesures de l'inhibition intracorticale et les habiletés cognitives et motrices chez les patients atteints de sclérose en plaques.Méthodes: 36 patients ayant une forme de sclérose en plaques récurrente-rémittente ont été recrutés par une clinique spécialisée et ont subi une évaluation de leur habiletés motrices et cognitives en utilisant l'Échelle de composé fonctionnel de la sclérose en plaques. Des périodes de silence cortical (PSc) et l'inhibition intracorticale de court intervalle (IIcI) furent mesurées dans les deux hémisphères en utilisant la stimulation transcrânienne magnétique. 13 sujets normaux ont également été évalués avec les mêmes mesures. Nous avons calculé les corrélations entre les résultats fonctionnels et neurophysiologiques, et avons évalué les asymétries hémisphériques. Résultats: Les patients avec une sclérose en plaques rémittente possèdent des PSc d'une durée significativement plus longue (101.6±29.2msec) que les sujets normaux (82.2±22.4ms, t(47)=-2.166, p=0.035), ce qui indique une augmentation de l'inhibition intracorticale. Une inhibition plus grande est associée avec des fonctions manuelles moins bonnes telles que mesurées par le test de dextérité manuelle de neuf-trous (main dominante: ρ=0.360, p=0.031; main non-dominante : ρ=0.351, p=0.039). Généralement, la durée PSc est comparable entre les hémisphères cérébraux dans le groupe de patients (t(69)=0.633, p=0.529). Cependant, parmi les patients ayant une asymétrie hémisphérique significative pour la durée des PSc, la direction de cette asymétrie prédit une asymétrie pour la fonction manuelle (ρ=0.950, p<0.001). Conclusion: Ces résultats supportent l'hypothèse que les changements dans l'inhibition corticale chez les patients atteints de sclérose en plaques reflètent le dommage des systèmes inhibitoires. Dans le contexte de nos découvertes précédentes, nos résultats indiquent également que l'inhibition corticale pourrait changer en ce qui concerne le stade de la maladie, et que les mécanismes reliés à ces changements pourraient différer dépendamment du stade. Nous ne pouvons omettre la possibilité que la augmentation de l'inhibition corticale durant la phase récurrente ou autre sous-forme de SP puisse être compensatoire. Il pourrait être utile de prendre en considération les marqueurs neurophysiologiques tels que la PSc afin de prédire la sévérité de la maladie.
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Boassa, Daniela. "Functional properties of aquaporin-1 ion channels in choroid plexus". Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280588.
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Aquaporins (also known as water channels) are members of the Major Intrinsic Protein family. Ion channel function has been shown for several members of the aquaporin family and the related neurogenic gene product Big Brain. Aquaporin-1 (AQP1) is a transmembrane channel that mediates osmotically-driven water flux. Prior work demonstrated that AQP1 channels expressed in Xenopus oocytes mediate a cGMP-dependent cationic current. Based on amino acid sequence alignments with cyclic nucleotide-gated channels and cGMP-selective phosphodiesterases, I found that the efficacy of ion channel activation is decreased by mutations of AQP1 at conserved residues in the C-terminal domain (aspartate D237 and lysine K243). These data provide direct evidence for the involvement of the AQP1 carboxyl terminal domain in cGMP-mediated ion channel activation. Because the proportion of active AQP1 ion channels seen in heterologous expression systems is low, it was of fundamental importance to investigate the functional properties of this channel in a physiological context. Using rat choroid plexus, a brain tissue that secretes cerebral spinal fluid (CSF) and endogenously expresses abundant AQP1, I demonstrated the existence of native AQP1 ion channels that show properties similar to those described previously in the oocyte expression system. They mediate a cGMP-dependent cationic conductance, are blocked by cadmium, and show a single-channel conductance of 166 pS. Given the skull's rigidity, pathological increases in CSF secretion (tumors, hydrocephalus, stroke) can result in brain damage. In the choroid plexus several proteins work in concert to regulate CSF secretion. The findings presented in this dissertation are first to demonstrate that AQP1 mediates a cationic current in response to intracellular signals that regulate CSF secretion such as ANP signaling. Fluxes of water and Na⁺ across confluent choroid plexus cell monolayers showed a decreased flow rate following treatment with ANP, and Cd²⁺ reversed the inhibitory effect. These results suggest that activation and block of the AQP1-mediated ionic current may alter net fluid transport across the choroid plexus barrier, and therefore be physiologically relevant in the regulation of net fluid transport in choroid plexus. This places AQP1 as one of the important targets for clinical intervention in brain volume disorders.
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David, Lane Richard. "Functional neuroanatomy of pleasant and unpleasant emotion". Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284228.
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To investigate the basic neural circuitry underlying emotion, three brain imaging studies were performed using positron emission tomography and 15O-water. In each study subjects viewed pictures from the International Affective Picture System (IAPS). Study #1 examined the neural correlates of pleasant and unpleasant emotion in 12 healthy women. Compared to viewing neutral stimuli, viewing pleasant and unpleasant pictures were each associated with activation of thalamus, hypothalamus, midbrain and medial prefrontal cortex. Viewing pleasant pictures was also associated with activation of the head of the caudate nucleus and viewing unpleasant pictures was associated with activation of left medial temporal structures (amygdala, hippocampus and parahippocampal gyrus), bilateral extrastriate visual cortex, bilateral temporal poles and cerebellum. Study #2 examined the neural substrates of emotional valence, arousal and attention. Six healthy men were studied in twelve scan conditions generated from a 3 x 2 x 2 factorial design: 3 levels of valence (pleasant, unpleasant and neutral), 2 levels of arousal (high and low) and 2 levels of attention (easy and difficult distraction tasks). Subtraction of the low arousal pleasant and unpleasant conditions from the high arousal pleasant and unpleasant conditions revealed activation in the dorso-medial region of the thalamus and the medial prefrontal cortex. Activation of the medial prefrontal cortex was greater during the low distraction compared to the high distraction conditions. These results suggest that the thalamus and medial prefrontal cortex are activated as a function of the intensity of emotional arousal independent of valence. Study #3 examined the neural substrates of the experiential component of emotion using a selective attention paradigm. Ten healthy men viewed IAPS pictures as they attended either to their subjective emotional responses or the spatial location of the depicted scene. During attention to subjective emotional responses increased neural activity was elicited in rostral anterior cingulate cortex (BA32) and medial prefrontal cortex, right temporal pole, insula and ventral cingulate. Under the same stimulus conditions when subjects attended to spatial aspects of the pictures activation was observed in parieto-occipital cortex bilaterally. The findings indicate that the rostral anterior cingulate cortex participates in representing subjective emotional responses.
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Harvey-Girard, Erik. "Molecular and functional characterization of NR2 subunits of teleost NMDA receptors". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82891.
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Synaptic processing is essential for proper signal integration by sensory neurons. N-methyl-D-aspartate receptors (NMDAR) are ionotropic receptors located at the post-synaptic membrane. NMDARs are considered coincidence detectors because they need postsynaptic depolarisation and neurotransmitter release to open. Several extracellular and intracellular signalling molecules affect NMDARs, which leads to modulation of the synaptic strength. The work presented in this thesis describes sequences of NR2 subunits expressed in pyramidal cells of a sensory system in a gymnotiform fish and analyses the functions of recombinant NMDAR-2B.A rapid amplification cDNA ends (RACE) approach was modified to amplify three NMDAR NR2 subunits expressed in electrosensory lateral line (ELL) pyramidal cells of a weakly electric fish, the gymnotiform Apteronotus leptorhynchus .
The amino acid sequence of the NR2 subunits (aptNR2A/B/C) was determined and compared with the sequence of the murine NR2 subunits. This comparison revealed high levels of sequence conservation throughout the glutamate-binding domain and membrane spanning segments. Lower levels of sequence conservation in the amino- and carboxy-terminal domains (ATD and CTD) were found for the three subunits. However, several known regulation sites in the ATD and several serine/threonine and tyrosine phosphorylation sites in the CTD are conserved.
The functional properties of the apteronotid NMDAR-2B receptor were examined by co-expression of aptNR1 and aptNR2B in HEK293 cells. The recombinant aptNR1/NR2B receptors produced robust currents after stimulation with glycine and glutamate or NMDA. Electrophysiological measurements of the concentration dependencies for these agonists indicated that the agonist-binding sites on the apteronotid receptors are highly conserved, with agonist affinities nearly identical to those of the murine NMDAR-2B. The classical antagonist AP-V and hydrogen ions inhibit the fish NMDAR-2B similarly as they do for mammalian NMDAR-2B. The response kinetics of the fish receptor were also highly conserved, with deactivation rates for the aptNMDAR-2B receptor matching those of its murine homologue. Apteronotid and murine NMDA receptors displayed two functional differences. First, the voltage-dependent Mg++ block is slightly reduced. Second, the affinity of specific non-competitive antagonist ifenprodil for NR2B is also reduced.
These results suggest that the critical features of NMDAR structure and function were established before the evolutionary diversion of fish and higher vertebrates. They suggest also that several signalling mechanisms known to affect synaptic strength in the mammalian CNS are conserved in the apteronotid nervous system and have established the electrosensory system of gymnotiforms as an interesting model to study NMDAR functions in synaptic plasticity of a sensory system.
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Gingras, Jacinthe. "Agrin regulates the structural and functional maturation of an interneuronal synapse". Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85070.
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Agrin is a nerve-derived factor that plays an important role in the formation of the neuromuscular junction. Interestingly, it is also expressed in other regions of the developing central and peripheral nervous systems, and we postulated that agrin is also a synaptogenic factor at the interneuronal synapse. To address agrin's role at the interneuronal synapse, we focused on a well-characterized peripheral interneuronal synapse in the superior cervical ganglia (SCG) and made use of transgenic mice with targeted deletions of the agrin gene: the z+ agrin-deficient and the agrin null (AGD-/-) animals. Synapses in the SCG are made onto a homogenous population of postganglionic neurons, and synaptic transmission is cholinergic, fast, excitatory and mediated by postsynaptic aggregates of neuronal AChRs (nAChRs).We found that SCG neurons in culture express a type II transmembrane and neural-specific isoform of agrin, and that agrin is highly concentrated at interneuronal sympathetic synapses. We next tested agrin's synaptogenic role at the interneuronal synapse and found that synaptic transmission was defective in z+ agrin-deficient and AGD-/- SCG. Indeed, we demonstrated that excitatory postsynaptic potentials (EPSP) in AGD-/- SCG were significantly smaller than the ones recorded in the wild type SCG. Moreover, we noted that only a fraction of the AGD-/- postganglionic neurons fired action potentials (AP) upon presynaptic trunk stimulation. Consistent with the functional defect, we demonstrated that synapses were reduced in number and poorly differentiated in both agrin-mutant lines, and addback of recombinant z+ agrin rescued the synaptic phenotype in neural agrin-deficient and AGD-/- SCG cultures. Finally, depolarization of the AGD-/- cultured SCG neurons exacerbated the defect in postganglionic localization of the neuronal AChR. Thus, agrin is an essential regulator of interneuronal synaptogenesis in the peripheral nervous system, where it promotes the differentiation and stabilization of neuronal synapses.
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Soles, Jennifer. "Bilingualism: Experience-dependent functional and structural characteristics of the adult brain". Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=107845.
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The influence of second language (L2) acquisition on the organization of the brain has been examined behaviourally, functionally, and anatomically, and while there appear to be age-related effects on native-like attainment of an L2, studies have not yet been well controlled for age of acquisition (AOA) and proficiency when comparing bilingual and monolingual individuals. Capitalizing on the unique linguistic environment of Montreal, Quebec, this study compares simultaneous bilinguals, a group of individuals who have acquired two languages from birth, to monolinguals, a group of individuals who have acquired only one language from birth. This provides the opportunity to examine the effects of bilingualism on the brain, without the factor of AOA. Detailed behavioural measures, combined with functional and anatomical magnetic resonance imaging (MRI), were obtained to examine the differences bilinguals and monolinguals display in native language proficiency, cerebral activation during sentence reading, and white and gray matter density (GMD) in a voxel-based morphometry (VBM) analysis. Simultaneous bilingual and monolingual individuals demonstrated equivalent behavioural and functional patterns in their respective native languages and very few differences in the VBM analysis. A region of interest in left Heschl's gyrus emerged where GMD was greater in bilinguals than monolinguals, and further research is needed to understand the role of this region in early phonetic discrimination. This study adds insights about how early language experience may help shape brain function and structure.L'influence de l'acquisition d'une seconde langue (L2) sur l'organisation cérébrale a été examinée avec des mesures comportementales, fonctionnelles, et anatomiques. Ces études ont démontré qu'il existe des effets reliés à l'âge d'apprentissage (AOA) sur la réalisation d'une compétence maternelle dans une L2, mais celles-ci n'ont pas encore été bien contrôlées pour l'AOA et la compétence lorsqu'une comparaison des individus bilingues et monolingues. L'étude suivante tire profit de l'environnement linguistique unique que présente la ville de Montréal, en comparant un groupe d'individus bilingues simultanés, c'est-à-dire qui ont acquis deux langues dès la naissance, à un groupe d'individus monolingues, qui ont acquis seulement une langue dès la naissance. Cette comparaison nous offre l'opportunité d'examiner les effets du bilinguisme sur l'organisation cérébrale, sans le facteur de l'AOA. Des mesures comportementales détaillées, ainsi que des scans d'imagerie par résonance magnétique (IRM) fonctionnels et anatomiques, ont été obtenus pour examiner la compétence des bilingues et des monolingues, l'activité cérébrale pendant qu'ils lisaient des phrases dans leurs langues maternelles, et les concentrations de matière blanche et grise dans une analyse de morphométrie voxel-à-voxel (VBM). Les bilingues simultanés et les monolingues ont démontré des réponses équivalentes pour les mesures comportementales et l'activation fonctionnelle dans leurs langues maternelles respectives, et l'analyse VBM a démontré peu de différences. Le gyrus de Heschl dans l'hémisphère gauche s'est présenté comme étant une région d'intérêt où la concentration de matière grise est plus grande chez les bilingues comparativement aux monolingues. Des recherches supplémentaires sont nécessaires afin de mieux comprendre le rôle de cette région cérébrale dans la discrimination phonétique d'une langue pendant la petite enfance. Cette étude vise à contribuer à la recherche existante en offrant un autre point de vue sur la façon dont l'expérience de la langue, acquise dès un jeune âge, influence la fonction et la structure cérébrale.
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Nikbakht, Nasrabadi Nader. "Visual Tactile Integration in Rats and Underlying Neuronal Mechanisms". Doctoral thesis, SISSA, 2015. http://hdl.handle.net/20.500.11767/4898.
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Our experience of the world depends on integration of cues from multiple senses to form unified percepts. How the brain merges information across sensory modalities has been the object of debate. To measure how rats bring together information across sensory modalities, we devised an orientation categorization task that combines vision and touch. Rats encounter an object–comprised of alternating black and white raised bars–that looks and feels like a grating and can be explored by vision (V), touch (T), or both (VT). The grating is rotated to assume one orientation on each trial, spanning a range of 180 degrees. Rats learn to lick one spout for orientations of 0±45 degrees (“horizontal”) and the opposite spout for orientations of 90±45° (“vertical”). Though training was in VT condition, rats could recognize the object and apply the rules of the task on first exposure to V and to T conditions. This suggests that the multimodal percept corresponds to that of the single modalities. Quantifying their performance, we found that rats have good orientation acuity using their whiskers and snout (T condition); however under our default conditions, typically performance is superior by vision (V condition). Illumination could be adjusted to render V and T performance equivalent. Independently of whether V and T performance is made equivalent, performance is always highest in the VT condition, indicating multisensory enhancement. Is the enhancement optimal with respect to the best linear combination? To answer this, we computed the performance expected by optimal integration in the framework of Bayesian decision theory and found that most rats combine visual and tactile information better than predicted by the standard ideal–observer model. To confirm these results, we interpreted the data in two additional frameworks: Summation of mutual information for each sensory channel and probabilities of independent events. All three analyses agree that rats combine vision and touch better than could be accounted for by a linear interaction.
Electrophysiological recordings in the posterior parietal cortex (PPC) of behaving rats revealed that neuronal activity is modulated by decision of the rats as well as by categorical or graded modality-shared representations of the stimulus orientation. Because the population of PPC neurons expresses activity ranging from strongly stimulus-related (e.g. graded in relation to stimulus orientation) to strongly choice-related (e.g. modulated by stimulus category but not by orientation within a category) we suggest that this region is involved in the percept-to-choice transformation.
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Liu, Ting Ting. "Spinal interneurons in sensorimotor integration". Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/1299/.
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Even though spinal cord research has expanded enormously during the past decades, we still lack a precise understanding of how spinal interneuron networks perfectly integrate sensory feedback with motor control, and how these neuron circuits give rise to specific functions. The present study thus has three basic aims: (1) to investigate propriospinal interneurons connecting rostral and caudal lumbar spinal cord in the rat; (2) to investigate input properties of identified spinal interneurons interposed in different pathways; (3) to investigate cholinergic terminals in the ventral horn of adult rat and cat. To realize the first aim, the B-subunit of cholera toxin (CTb) was injected into the motor nuclei at the L1 or L3 segmental level to retrogradely label propriospinal interneurons in the L5 segment of rat spinal cord. These cells had a clear distribution pattern which showed that they were located mainly in ipsilateral dorsal horn and contralateral lamina VIII. A series triple-labelling experiments revealed that about 1/4 of the CTb-positive cells were immunoreactive for calbindin and/or calretinin. It was also found that a small population of CTb labelled cells were cholinergic and were observed mainly in three locations: lamina X, the medial part of intermediate zone and lamina VIII. In addition, injection of CTb also anterogradely labelled axon terminals, which arose from the commissural interneurons (CINs) within the site of injection, crossed the midline and aroborized in the contralateral lateral motor nuclei of the L5 segment. The neurotransmitter systems in labelled axon terminals of CINs were investigated by using antibodies raised against specific transmitter-related proteins. The results showed that approximately 3/4 terminals were excitatory and among those excitatory terminals about 3/4 forming contacts with motoneurons. To achieve the second aim, 21 interneurons located in the intermediate zone and lamina VIII from 7 adult cats were characterised electrophysiologically and labelled intracellularly with Neurobiotin. Seventeen of these cells were activated monosynaptically from primary muscle afferents but the remaining four cells received monosynaptic inputs from the medial longitudinal fasciculus (MLF). Quantitative analysis revealed that cells in the first group received many contacts from excitatory terminals that were immunoreactive for the vesicular glutamate transporter 1 (VGLUT1) but those cells from the second group received few contacts of this type and were predominantly contacted by terminals immunoreactive for vesicular glutamate transporter 2 (VGLUT2). This result was as predicted because VGLUT1 is found principally in the terminals of myelinated primary afferent axons whereas VGLUT2 is located in the terminals of interneurons in the spinal cord. Interneurons in the first group were then characterised as excitatory and inhibitory on the basis of the transmitter content contained within their axon terminals. Although there was a greater density of VGLUT1 contacts on excitatory rather than inhibitory cells, the difference was not statistically significant. GABAergic terminals formed close appositions with VGLUT1 contacts on both excitatory and inhibitory cells. These appositions were likely to be axoaxonic synapses which mediate presynaptic inhibition. In addition, the densities of VGLUT1 and VGLUT2 contacts on 30 dorsal horn CINs and 60 lamina VIII CINs that were retrogradely labelled with CTb from 3 adult rats were compared. The results showed that VGLUT2 terminals formed the majority of excitatory inputs to both dorsal horn and lamina VIII CINs but dorsal horn CINs received a significantly greater density of VGLUT1/2 inputs than lamina VIII CINs. In order to achieve the third aim, i.e. whether glutamate is a cotransmitter at motoneuron axon collateral terminals in the ventral horn, a series of anatomical experiments were performed on axon collaterals obtained from motoneurons from an adult cat and retrogradely labelled by CTb in adult rats. There was no evidence to support the presence of vesicular glutamate transporters in motoneuron axon terminals of either species. In addition, there was no obvious relationship between motoneuron terminals and R2 subunit of the AMPA receptor (GluR2). However, a population of cholinergic terminals in lamina VII, which did not originate from motoneurons, was found to be immunoreactive for VGLUT2 and formed appositions with GluR2 subunits. These terminals were smaller than motoneuron terminals and, unlike them, formed no relationship with Renshaw cells. The evidence suggests that glutamate does not act as a cotransmitter with acetylcholine at central synapses of motoneurons in the adult cat and rat. However, glutamate is present in a population of cholinergic terminals which probably originate from interneurons where its action is via an AMPA receptor. In conclusion, the present studies add to the understanding of the organization of neuronal networks involved in sensorimotor integration. Propriospinal interneurons located within the lumbar segments have extensive intra-segmental projections to motor nuclei. First order interneurons interposed in reflex pathways and descending pathways receive a significantly different pattern of inputs. A similar proportion of monosynaptic excitatory input from primary afferents has been found in both excitatory and inhibitory interneurons and these two types of cells are subject to presynaptic inhibitory control of this input.
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Soni, Mayur. "Building corporate brand orientation through cross-functional integration within marketing brand orientation through cross-‐functional integration within marketing". Diss., University of Pretoria, 2010. http://hdl.handle.net/2263/26355.
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Prior research defines brand orientation as an approach in which the processes of the organization revolve around the creation, development and protection of brand identity in an ongoing interaction with target customers with the aim of achieving lasting competitive advantages in the form of brands (Urde, 1999). This research paper examines how marketing managers perceive corporate brand orientation with a Financial services company, namely Standard Bank Group Limited (Standard Bank) and what influence cross-functional integration has in enhancing the level of brand orientation. The study design was non-experimental and convenience sampling used. The data was collected within the Group and South African marketing functions of Standard Bank both of which are located within South Africa. The survey was delivered to 131 respondents across 30 marketing functions with the unit of analysis being each employee within their respective teams. The research results indicate that cross-functional integration variables of compensation, multifunctional training and cross-functional teams have a positive influence on brand orientation. The findings from this research can contribute to the body of knowledge within the domain of building corporate brand orientation within the financial services industry, specifically with regards to implications for marketing leadership in terms of improving the performance of the marketing department.Dissertation (MBA)--University of Pretoria, 2010.
Gordon Institute of Business Science (GIBS)
unrestricted
29
Sauvé, Yves. "Reformation of functional synapses in the retino-collicular pathway of adult hamsters". Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28910.
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The functional reconstruction of interrupted CNS pathways in mature mammals was studied in adult hamsters in which retinal ganglion cells (RGCs) regenerated axons through a peripheral nerve graft directed from the stump of the cut optic nerve to the superior colliculus (SC). Visually elicited unitary responses of both pre- and postsynaptic origin were recorded in the reinnervated SC and were discriminated by selectively abolishing postsynaptic activity using GABA microiontophoresis. Activity from individual regenerated axonal arbors and from the neurons within their terminal field of innervation was confined to the superficial retinorecipient SC layers and could be recorded over a range of up to 200 $ mu$m in all planes. Analysis of such electrophysiological recordings suggests that the terminal arborizations of single regenerated RGC axons can establish functional synapses with several SC neurons and that the convergence of inputs from regenerated RGC axons is not required for the activation of SC neurons in response to light. Functional synapses established between regenerated RGC axons and SC neurons persisted for up to 60 weeks after grafting. Visually elicited responses were recorded in the contralateral SC from the regenerated projections of as many as 63 different RGCs. The extent of functional innervation by regenerated retinal axons accessing the SC at a single entry point covered up to 0.8 mm and 1.2 mm in the caudo-rostral and latero-medial planes, respectively. Despite large scale targeting errors in the functional reinnervation of the SC, the re-established retinal projections in the SC were not randomly deployed along the caudo-rostral axis. There was an overall tendency for the relative naso-temporal position of any two RGCs to be appropriately represented by their respective regenerated inputs in the SC along its caudo-rostral axis. This suggests that regenerating RGC axons may recognize caudo-rostral positional markers as they reinnervate the SC.
30
Li, He 1952. "Functional roles of adenosine in synaptic transmission in the hippocampus in vitro". Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41678.
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This thesis focuses on the functional roles of adenosine on neuronal excitability and synaptic transmission in the rat hippocampal CA1 region in vitro. Hippocampal slices were placed in an interface recording chamber and constantly superfused with oxygenated artificial cerebral fluid at $30 sp circ$C. Intracellular (current-clamp) recording techniques were used to measure the spontaneous and evoked inhibitory and excitatory synaptic potentials as well as resting membrane potential and input resistance.Our findings indicate that adenosine induces the opening of potassium channels in the postsynaptic membrane of CA1 neurones, including $ rm K sb{ATP}$ channels. Adenosine-induced attenuation of EPSPs and poly-synaptic IPSPs may be due to the activation of adenosine $ rm A sb1$ receptors at both the pre- and postsynaptic sites of excitatory synapses onto the pyramidal cells and interneurones. On interneurones, adenosine appears to have two different effects: one is a hyperpolarization and decrease in input resistance, similar to the inhibitory effect on pyramidal cells, and the other is a depression of the amplitude and duration of afterhyperpolarization which characterizes the action potential of these interneurones. A scheme is proposed in which adenosine $ rm A sb1$ receptors may be present at pre- and postsynaptic sites of excitatory synapses but not at presynaptic sites of inhibitory synapses. Adenosine was also found to tonically inhibit spikes associated with NMDA receptor activation and that at least some of these NMDA receptors may be present in the dendritic trees of the pyramidal cells. The slow excitatory effects of adenosine may be due to activation of adenosine $ rm A sb2$ receptors at both pre- and postsynaptic sites in the hippocampal CA1 region.
The inhibitory and excitatory effects of adenosine on CA1 pyramidal cells and inhibitory effects of adenosine on interneurones suggest that adenosine may be a homeostatic neuromodulator regulating neuronal excitability and synaptic transmission in the hippocampus in mammalian brain.
31
Hamam, Bassam. "Functional organization of entorhinal cortex layer V neurons : electrophysiological and morphological characterization". Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38488.
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The entorhinal cortex occupies an important anatomical position in the temporal lobe as the interface between the hippocampus and the neocortex. Its superficial cell layers funnel the cortical input into the hippocampus while the deep layer V is the major target of hippocampal output, which it then directs back to the cortex. This connectivity alone makes the entorhinal cortex a crucial element in what is known as the neocortical-hippocampal-neocortical circuit, a system involved in the long-term storage of "declarative" memories. However, the detailed analysis of the morphological and electrophysiological characteristics of cells in entorhinal cortex layer V had not been carried out, information that is necessary to understand how this cortical layer may participate in the processing of cortically directed hippocampal information. The main goal of the present study was thus to carry out by means of intracellular recording and labelling in a "in vitro" rat entorhinal cortex slice preparation an extensive characterization of the intrinsic electrophysiological characteristics of entorhinal cortex layer V principal neurons in correlation with their morphological attributes. Our main working hypothesis was that electrophysiologically, similar to the neocortex, layer V principal neurons in both the medial and lateral subdivisions of the entorhinal cortex would constitute a heterogeneous population comprised of regularly spiking cells and intrinsically bursting neurons.We found layer V of the entorhinal cortex to be comprised of three main cellular subtypes, pyramidal, horizontal and polymorphic neurons, that were electrophysiologically non-distinguishable. Cells in both medial and lateral entorhinal areas had similar morphological and electrophysiological properties. No intrinsically bursting neurons were encountered; instead, cells were classified as regular spiking neurons with varying spike-frequency adaptation. We also found that most layer V neurons displayed persistent Na+ current (INap) dependent subthreshold membrane potential oscillations; a mechanism that might endow layer V cells with a functional contribution to network rhythmicity.
32
Zive, Kevin. "Integration of visual and auditory spatial stimuli in the blind field of hemispherectomy patients". Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=20615.
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The effect of multisensory integration in the blind field of hemispherectomy patients was investigated in order to examine the possible involvement of the superior colliculus in blindsight. The superior colliculus may be responsible for residual abilities in the blind field because of its predominant subsidiary visual connections with the retina. Ten normal subjects and four patients with a temporal lobe removal served as controls for four experimental subjects (two hemispherectomized and two partial hemispherectomized). The experiment tested three tasks that measured reaction time and localization accuracy: (1) visual target only; (2) auditory target only; (3) simultaneous auditory and visual (aud/vis) stimuli at the same location. Only reaction time was measured in the condition where simultaneous presentations of aud/vis stimuli were made at different locations. The existence of blindsight was substantiated for localization, but not for reaction time in the blind field of hemispherectomy patients. None of the subjects demonstrated multisensory integration for reaction time and localization accuracy. Our results indicate that multisensory integration did not take place, at least with the types of stimuli used here. A role of the superior colliculus in blindsight remains possible since the hemispherectomy subjects still showed unconscious residual visual abilities in their blind field.
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Biswas, Amitava. "Perioral sensorimotor integration in Parkinson's disease". [Bloomington, Ind.] : Indiana University, 2005. http://wwwlib.umi.com/dissertations/fullcit/3183913.
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Achim, Amélie M. "Functional brain imaging of episodic memory in schizophrenia and first episode of psychosis". Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111847.
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Memory is one of the cognitive functions that is most affected in schizophrenia and memory dysfunctions have a major impact on the functioning and quality of life of these patients. Functional brain imaging can help us identify the brain structures that are affected during the performance of a memory task. Identifying these regions can help us identify the specific cognitive processes that are affected in schizophrenia. To this end, I performed a meta-analysis of published functional brain imaging studies of episodic memory in schizophrenia. This meta-analysis showed that the prefrontal cortex and the medial temporal lobes are the brain regions that are most consistently reported as being affected in schizophrenia during the performance of a memory task. Most studies however used a low-level baseline condition that did not target a specific cognitive process. In addition, they included patients with a long-term history of schizophrenia, leaving open the possibility that factors linked to illness chronicity could have influenced the pattern of results. Based on the insights gleaned from the meta-analysis, I performed a functional magnetic resonance imaging study of episodic memory encoding in patients with a first episode of a schizophrenia spectrum psychosis (FEP) and healthy subjects. Three processes known to be involved in memory encoding were targeted, namely associative processing, semantic associative novelty and encoding success. In healthy subjects, both associative processing and semantic associative novelty were associated with increased activation in the medial temporal lobes, with no interaction between these two variables. In people with FEP, encoding success and associative processing revealed intact patterns of prefrontal and medial temporal lobe activation. In contrast, semantic associative novelty was associated with a marked reduction in medial temporal activation. The identification of selectively intact and deficient processes involved in memory encoding has potential clinical relevance for the development of more focused cognitive remediation strategies.
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Allaire, Patrick. "Biochemical and functional characterization of connecdenn and its DENN domain in intracellular trafficking". Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66644.
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Endocytosis and vesicle trafficking are essential for cellular division, differentiation and survival. Following endocytosis, cargo is delivered to the sorting endosome, where it is selected for degradation or recycled back to the cell surface. The various trafficking steps within the endosomal system are regulated by Rabs, small GTPases, which toggle between an inactive GDP-loaded conformation and an active GTP-loaded conformation. Clathrin-mediated endocytosis (CME) allows cargo internalization and coupling to the endosomal system via formation of clathrin-coated vesicles (CCVs). Connecdenn was identified as a component of clathrin-coated vesicles (CCVs) isolated from developing rat brain. The C-terminus of connecdenn is predicted to be unstructured and encodes several binding motifs that bind to the CME proteins intersectin1, endophilinA1 and AP-2. Connecdenn is enriched in brain, localizes to synapses, and its knockdown in hippocampal cultures inhibits synaptic vesicle recycling. Connecdenn enriches strongly on CCVs and is stably associated with the CCV membrane after removal of its clathrin coat. The stable membrane association of connecdenn depends on the N-terminal DENN domain, an evolutionary conserved but uncharacterized tri-partite domain. The DENN domain also functions as a guanine nucleotide exchange factor (GEF) for Rab35, which regulates cargo recycling. In fact, in non-neuronal cells, connecdenn and Rab35 do not regulate CME but control the recycling of cargo from sorting endosomes. Curiously, connecdenn/Rab35 specifically control the recycling of MHCI, which enters the cell independently of CME but do not influence the trafficking of the transferrin receptor, a prototypical CME cargo. Overall, my thesis work on connecdenn has allowed us to appreciate three important conclusions. First, connecdenn is a CCV protein that functions at the neuronal synapse to regenerate SVs. Second, connecdennLe trafic intracellulaire est un processus essentiel pour la division, différenciation et survie cellulaire. Suite à l'endocytose, le cargo est acheminé vers l'endosome de triage qui le dirigera vers la voie de dégradation ou le recyclera à la surface de la cellule. Le trafic endosomal est régi par les petites GTPases Rab, basculant entre la conformation inactive GDP-chargé et active GTP-chargé. Dans l'endocytose tributaire pa r la clathrine (ETC), la formation de vésicules tapissées de clathrine (VTC) permet l'internalisation du cargo et son couplage au système endosomal. La protéine Connecdenn a été identifiée comme composante des VTCs. L'extrémité C-terminale de Connecdenn est prédite etre non structurée et code plusieurs motifs d'interaction avec les protéines impliquées dans l'ETC comme intersectin1, endophilinA et AP-2. Connecdenn est enrichie sur les VTCs. Lorsque le manteau de clathrine est dissocié, l'association de Connecdenn avec la membrane des VTC demeure stable. Cette association et son recrutement dans les VTCs s'effectuent grâce à son extrémité C-terminale et s'avèrent nécessaires pour le recyclage des vésicules synaptiques. Par contre, l'association de Connecdenn avec la membrane des VTCs dépend de son domaine DENN N-terminal, dont la fonction n'a pas encore été caractérisée. Ce domaine fonctionne également comme un facteur d'échange guanine (FEG). En fait, dans les cellules non-neuronales, Connecdenn et Rab35 ne régularisent pas l'ETC, mais plutôt le recyclage du cargo à partir des endosomes de triage. De plus, l'épuisement de Connecdenn ou Rab35 perturbe spécifiquement le recyclage de MHCI, dont l'internalisation n'est pas régie par l'ETC. Toutefois, l'absence de Connecdenn ou de Rab35 n'a aucune influence sur le trafic du récepteur de la transferrine, cargo typique de l'ETC. Mon travail sur Connecdenn se résume a trois conclusions generales;
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Dawson, Debra. "Evaluation and calibration of functional network modeling methods based on known anatomical connections". Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114238.
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Recent studies have identified large scale brain networks based on the spatio-temporal structure of spontaneous fluctuations in resting-state fMRI data. It is expected that functional connectivity based on resting-state data is reflective of- but not identical to the underlying anatomical connectivity. However, which functional connectivity analysis methods reliably predict the network structure remains unclear. Here we tested and compared network connectivity analysis methods by applying them to fMRI resting-state time-series obtained from the human visual cortex. The methods evaluated here are those previously tested against simulated data in Smith et al. (Neuroimage, 2011).To this end, we defined regions within retinotopic visual areas V1, V2, and V3 according to their eccentricity in the visual field, delineating central, intermediate, and peripheral eccentricity regions of interest (ROIs). These ROIs served as nodes in the models we study. We based our evaluation on the 'ground-truth', thoroughly studied retinotopically organized anatomical connectivity in the monkey visual cortex. For each evaluated method, we computed the fractional rate of detecting connections known to exist ('c-sensitivity'), while using a threshold of the 95th percentile of the distribution of interaction magnitudes of those connections not expected to exist. Under optimal conditions, including session duration of 68 minutes, a relatively small network consisting of 9 nodes and artifact-free regression of the global effect, each of the top methods predicted the expected connections with 75%-83% c-sensitivity. Partial Correlation performed best (PCorr; 83%), followed by Regularized Inverse Covariance (ICOV; 79%), Bayesian Network methods (BayesNet; 77%), Correlation (75%), and General Synchronization measures (75%). With decreased session duration, these top methods saw decreases in c-sensitivities, achieving 66%-78% and 60%-70% for 34 and 17 minute sessions, respectively. With a short resting-state fMRI scan of 8.5 minutes (TR = 2s), none of the methods predicted the real network well, with ICOV (53%) and PCorr (51%) performing best. With increased complexity of the network from 9 to 36 nodes, multivariate methods including PCorr and BayesNet saw a decrease in performance. However, this decrease became small when using data from a long (68 minutes) session. Artifact-free regression of the global effect significantly increased the c-sensitivity of all top-performing methods. In an overall evaluation across all tests we performed, PCorr, ICOV and BayesNet set themselves somewhat above all other methods. We propose that data-based calibration based on known anatomical connections be integrated into future network studies, in order to maximize sensitivity and reduce false positives.Des études récentes ont identifié des réseaux du cerveau à hautes-échelles basés sur la structure spatio-temporelle des fluctuations spontanées dans les donnés IRMf à l'état de repos. Il est prévu que la connectivité fonctionnelle basée sur des donnés de l'état de repos soit reflétée, sans être identique à la connectivité anatomique. Cependant, quelles méthodes analytiques de la connectivité fonctionnelle prédisent de manière fiable la structure du réseau n'est pas encore clair. Ici, nous avons testé et comparé des méthodes analytiques de la connectivité de réseaux en leur appliquant à des séries de temps IRMf de l'état de repos provenant du cortex visuel humain. Les méthodes évaluées ici sont celles qui ont été testées avec des données simulées dans l'article Smith et al. (Neuroimage, 2011). À cette fin, nous avons défini des sous-régions contenues dans les régions visuelles V1, V2, et V3 selon leur excentricité dans le champ visuel, en créant une région d'intérêt (RI) centrale, intermédiaire, et périphérique. Ces RI ont servi comme nœuds dans les modèles que nous étudions. Nous avons basé notre évaluation sur la « vérité » de l'anatomie du cortex visuel des singes macaques qui a déjà été étudié en profondeur. Pour chaque méthode évaluée, nous avons calculé le taux fractionnel de la détection des connections que nous savons existantes ('c-sensitivité'), en utilisant un seuil étant défini comme le 95e percentile de la distribution des magnitudes d'interactions des connections que nous savons inexistantes.Sous conditions optimales, incluant une longueur de session de 68 minutes, un réseau de 9 nœuds et la régression sans artéfact de l'effet global, les méthodes les plus efficaces ont prédit les connections attendues avec une c-sensitivité de 75%-83%. La corrélation partielle était meilleure (PCorr; 83%), suivi par la Covariance Inverse Régularisé (ICOV; 79%), les méthodes de Réseau Bayesien (BayesNet; 77%), la corrélation (75%), et la Synchronisation Générale (GenSynch; 75%). Avec des sessions plus courtes, les meilleures méthodes ont vus des abaissements en c-sensitivité, réussissant seulement 66%-78% et 60%-70% pour des sessions de 34 et 17 minutes respectivement. Avec des sessions IRMf à l'état de repos courtes de 8.5 minutes (TR=2s), aucune méthode n'a prédit notre réseau avec succès; ICOV (53%) et PCorr (51%) ont été meilleurs. Quand nous avons augmenté la complexité du système en regardant 18 ou 36 nœuds en même temps, les méthodes multi-variantes incluant PCorr et BayesNet ont moins bien réussi qu'avec seulement 9 nœuds. La régression sans artéfact de l'effet global améliore significativement la c-sensitivité de toutes les meilleures méthodes. Dans une évaluation générale à travers tous nos tests, PCorr, ICOV, et BayesNet se séparent des autres en étant les meilleurs.Nous proposons qu'une calibration basée sur les donnés utilisant des connections anatomiques connues soit intégrée dans les futures études de réseaux pour maximiser la sensitivité des résultats et réduire la présence de faux positifs dans les réseaux prédits.
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Dias, Angelo Ridge. "Cognitive therapy, working memory training, and the treatment of Methamphetamine Use Disorder - a functional MRI study". Master's thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/32647.
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Background: In recent years, methamphetamine use disorder (MUD), which is associated with adverse outcomes and represents a significant public health burden, has become highly prevalent in Cape Town, South Africa. Protracted methamphetamine (MA) use has been linked with neural dysfunction and working memory deficits. Although current treatments have shown limited efficacy in addressing MUD, recent evidence indicates the potential of utilizing tailored brief cognitive therapy programs and working memory training to improve outcomes. The current study aims to investigate the potential impact of brief cognitive therapy and using working memory training as an adjunct in the treatment of MUD. Methods: Participants were recruited from an in-patient drug rehabilitation centre in Cape Town. The sample (n = 26) consists of male patients (between the ages of 18–50) diagnosed with MUD. MUD patients were randomly split into 2 groups that received 4 weeks of treatment, i.e. treatment as usual (cognitive therapy only (NT) (n= 12)) and cognitive therapy with working memory training (CT) (n = 14). Neuroimaging and psychological data were collected from participants pre- and post- intervention to assess the relative impact of said interventions. Results: Behavioural outcome measures and the n-back working memory task adapted for fMRI were measured and compared pre- and post- intervention. No significant differences were present between groups prior treatment on behavioural measures, demographic measures, and fMRI activity. The brief cognitive therapy appeared to reduce depression and impulsivity scores over the course of the intervention, with scores slightly lower in the CT group. An FDR corrected whole-brain repeated measures ANOVA on the main effect of group indicated significant activation in the left posterior cingulate, left anterior cingulate, and left lingual gyrus. Post hoc t-tests were then conducted to follow up the group main effect and significant differences under FDR correction were observed in the NT group (in contrast to the CT group) indicating significantly more activity in the left superior temporal gyrus, left insula, right posterior declive, and right lingual gyrus. Significant differences were also observed under FDR correction on a posthoc test on the CT group (in contrast to the NT group) indicating significantly less activity in the left lingual gyrus, left posterior declive, and right cuneus. 5 Conclusions: The findings tentatively suggest that the working memory training adjunct may have slightly enhanced working memory maintenance brain function relative to the treatment as usual group post-intervention. The evidence also suggests that there may have been inefficient neural functioning in the treatment as usual group during the working memory task compared to the group receiving the working memory training adjunct. The results demonstrated that brief cognitive therapy treatment did somewhat reduce depressive symptoms and impulsivity in this study, with indications of subtle treatment gains in the cognitive training group. Overall, the current study (despite numerous limitations) provides preliminary and tentative evidence of the possible benefits of brief term cognitive therapy and the potential promise of using working memory training as a treatment adjunct.
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Swettenham, Jennifer B. "Functional neuroimaging and behavioural studies on global form processing in the human visual system". Thesis, Aston University, 2005. http://publications.aston.ac.uk/14544/.
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Magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI) and behavioural experiments were used to investigate the neural processes underlying global form perception in human vision. The main findings from normally-sighted observers were: 1) sensitivity to horizontal structure was less than for radial or rotational structure; 2) the neural response to global structure was a reduction in cortical oscillatory power (10-30 Hz) within a network of extrastriate areas, including V4 and V3a; 3) the extend of reduced cortical power was least for horizontal patters; 4) V1 was not identified as a region of peak activity with either MEG or fMRI. The main findings with the strabismic amblyope were: 1) sensitivity for detection of radial, rotational, and horizontal structure was reduced when viewed with the amblyopic- relative to the fellow- eye; 2) cortical power changes within V4 to the presentation of rotational Glass patterns were less when viewed with the amblyopic- compared with the fellow- eye. The main conclusions are: 1) a network of extrastriate cortical areas are involved in the analysis of global form, with the most prominent change in neural activity being a reduction in oscillatory power within the 10-30 Hz band; 2) in strabismic amblyopia, the neuronal assembly associated with form perception in extrastriate cortex may be dysfunctional, the nature of this dysfunction may be a change in the normal temporal pattern of neuronal discharges; 3) MEG, fMRI and behavioural measures support the notion that different neural processes underlie the perception of horizontal as opposed to radial or rotational structure.
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Cheung, Man-hin Matthrew, e 張文騫. "Development of diffusion and functional magnetic resonance imaging techniques for neuroscience". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47147635.
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Parise, Cesare Valerio. "Signal compatibility as a modulatory factor for audiovisual multisensory integration". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:ec36fab1-9209-4579-a043-6f990b7ec553.
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The physical properties of the distal stimuli activating our senses are often correlated in nature; it would therefore be advantageous to exploit such correlations to better process sensory information. Stimulus correlations can be contingent and readily available to the senses (like the temporal correlation between mouth movements and vocal sounds in speech), or can be the results of the statistical co-occurrence of certain stimulus properties that can be learnt over time (like the relation between the frequency of acoustic resonance and the size of the resonator). Over the last century, a large body of research on multisensory processing has demonstrated the existence of compatibility effects between individual features of stimuli from different sensory modalities. Such compatibility effects, termed crossmodal correspondences, possibly reflect the internalization of the natural correlation between stimulus properties. The present dissertation assesses the effects of crossmodal correspondences on multisensory processing and reports a series of experiments demonstrating that crossmodal correspondences influence the processing rate of sensory information, distort perceptual experiences and lead to stronger multisensory integration. Moreover, a final experiment investigating the effects of contingent signals’ correlation on multisensory processing demonstrates the key role of temporal correlation in inferring whether two signals have a common physical cause or not (i.e., the correspondence problem). A Bayesian framework is proposed to interpret the present results whereby stimulus correlations, represented on the prior distribution of expected crossmodal co-occurrence, operate as cues to solve the correspondence problem.
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Marshall, Victoria Louise. "Clinical and functional imaging correlates in Parkinson's disease". Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/7012/.
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Parkinson's disease (PD) is misdiagnosed throughout its disease course for conditions such as essential tremor, drug-induced parkinsonism, vascular pseudo-parkinsonism, Alzheimer's disease and other degenerative parkinsonian diseases. This thesis aims to verify the accuracy of dopaminergic imaging in early and uncertain parkinsonian/tremor disorders through 3 studies. The first is a prospective United Kingdom multicentre assessment of [1231] FP-CIT SPECT use in 190 patients in pre-defined diagnostic categories and with particular focus on clinical features to assess the influence of imaging in routine practice. The second is a 2 year follow-up study of 150 consecutive patients with normal SPECT, with specific attention to clinical progression and antiparkinson medication use, and includes focus on a subgroup who fulfilled PD criteria where successful antiparkinson medication withdrawal was achieved. The third is a multicentre prospective European study of the accuracy of [1231] FP-CIT SPECT in 99 patients that included serial clinical and imaging assessments. Notably, when initial diagnosis/scan mismatch cases occurred, and with awareness of the scan result, the clinician invariably changed the diagnosis in line with the scan result which confirms the considerable influence of imaging on the practising clinician. Parkinson's disease is clinically overdiagnosed early in its disease course, whereas imaging is more specific, in the vast majority of cases with normal dopaminergic imaging, there was no evidence of clinical or imaging progression which would be in keeping with degenerative parkinsonism.
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Duan, Huanan. "Synthesis, integration, and characterization of functional inorganic nanomaterials". Worcester, Mass. : Worcester Polytechnic Institute, 2009. http://www.wpi.edu/Pubs/ETD/Available/etd-052809-122349/.
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Dissertation (Ph.D.)--Worcester Polytechnic Institute.Keywords: electrodeposition; chemical vapor deposition; AAO template-assisted nanofabrication; 1 D nanomateirals; inorganic nanomaterials; nanostructured electrode. Includes bibliographical references (leaves 102-103).
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Adamsson, Niklas. "Mechatronics engineering : New requirements on cross-functional integration". Licentiate thesis, Stockholm, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-152.
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Greven, Inez Margot. "Functional integration of neural signals during person perception". Thesis, Bangor University, 2016. https://research.bangor.ac.uk/portal/en/theses/functional-integration-of-neural-signals-during-person-perception(bdd41d98-0326-4462-8c80-4d10e23939cc).html.
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In every day social interactions,it is important to know who other people are and how we might expect them to behave. Neuroscientific research has identified neuroanatomically distinct networks involved in perceiving a person’s physical features and reasoning about their trait characteristics. While it has been demonstrated that both these networks are engaged when linking multiple features of a person ogether, the neural networks integration under these circumstances has mostly been overlooked. Over four empirical chapters, this thesis aims to understand how functional integration between distinct cognitive and neural systems supports person perception during social interactions. The first empirical chapter (Chapter 3) investigates how physical features are linked to social knowledge, similarly to how we form impressions when we initially meet someone. While in this chapter social knowledge was inferred from descriptions of the person’s behaviour, Chapter 4 aimed to investigate how social signals are extracted from the visual image of the body alone. Chapter 5 investigated functional integration during the perception of bodies that cued recall of social knowledge. Finally, Chapter 6 differentiated between affective valences of trait-‐based judgments. Taken together, the findings presented in this thesis highlight the importance of an integrative perspective when investigating the role of functionally segregated brain regions in a large interconnected network. This view advocates the use offunctional connectivity measures when investigating the role of person perception nodes in socially complex settings.
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Sampaio, Baptista Silvia Cassandra. "Imaging structural and functional brain changes associated with long-term learning". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:eec1c1ac-f951-4133-aa2e-53a1eeab4fae.
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Learning induces functional and structural plasticity. This thesis used a range of neuroimaging approaches in both humans and rodents to address three main questions: (1) Can we predict learning performance using baseline imaging measures? (2) To what extent do performance outcomes or training amount determine experience-dependent plastic changes? (3) What biological mechanisms underlie white matter plasticity detected using MRI? Effects of performance and amount of practice on brain structure were studied by varying the amount of juggling practice. Brain structure was found to predict performance on a complex juggling task before learning acquisition. Both performance and practice were found to affect brain structure after learning. Overall, participants that achieved higher performances had higher grey matter (GM) and WM matter change. Also, participants that trained juggling for longer had higher positive brain changes than participants that practiced less. The effects of juggling performance and practice in functional connectivity and GABA levels as measured by MR spectroscopy (MRS) were also investigated. High intensity training was found to decrease the motor resting-state network strength while lower intensity increased the network strength. The increase in strength was associated with a decrease in GABA concentration. A correlation was also found between motor resting-state strength change and GABA concentration change after learning. Finally, since WM plasticity has not been thoroughly investigated and to understand which cellular events underlie WM change, an animal model of motor learning was combined with diffusion tensor imaging (DTI) and immunohistochemistry. Learning a novel motor task increased WM fractional anisotropy, an indirect measure of WM microstructure, in the contralateral hemisphere to the used paw. Immunohistochemistry staining with myelin basic protein (MBP) antibody of this region revealed higher myelin stain intensity for the learning group that correlated with performance in the task.
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You, Wenjia. "Lineage and Functional Analyses of Specific Subsets of Retinal Progenitor Cells". Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467533.
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The vertebrate central nervous system (CNS) is made up of a diverse array of cell types. The retina, an accessible part of the CNS with seven major cell types and more than sixty cell subtypes, is an excellent model system to study cell fate determination in the CNS. Previous retroviral lineage tracing experiments have demonstrated that retinal progenitor cells (RPCs) are multipotent, and give rise to clones of variable sizes and cell type compositions. Two models are proposed to explain this variability in clone size and composition: One model states that there are different subsets of RPCs, whose distinctive molecular profiles determine their daughter cell fates, while the other model argues that RPCs are equipotent and daughter cell types are determined by environmental cues and/or stochastic cellular processes.
To test the hypothesis on distinct RPCs, we first asked whether we could identify specific RPC subsets that would produce specific daughter cell types. We made use of 10 molecular markers to mark specific RPC subsets, and traced individual subsets' daughter cell fates with Cre-recombinase fate mapping and retroviral lineage tracing. A novel RPC subset, which express the basic helix-loop-helix (bHLH) transcription factor Ngn2, were found to be heavily biased towards generating rod photoreceptors and amacrine cells in terminal divisions in the postnatal mouse retina.
Next, we partitioned the postnatal RPC pool into different RPC subsets with molecular marker Ngn2 and Olig2, and probed individual subsets' responsiveness to misexpression of two sets of transcription factors, which are known to play important roles in retinal cell fate determination. We have shown that different RPC subsets respond differently to the same genetic perturbation, which is indicative of their distinctive intrinsic capabilities to generate certain daughter cell types.
Together, we have shown that in the mouse retina, the RPC pool is composed of distinct RPC subsets, each of which have unique molecular profiles, give rise to specific daughter cell types, and respond differently to perturbations. This study provides new insight into cell fate determination in the retina, and may shed light on a more general mechanism of cell fate determination in a variety of systems.Medical Sciences
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Ditchfield, Jennifer A. "The assessment of functional communication in patients with acquired communication problems : the development of the Derby Functional Communication Scale". Thesis, University of Nottingham, 2008. http://eprints.nottingham.ac.uk/10612/.
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The Derby Functional Communication Scale (DFCS) was developed to assess functional communication in patients in hospital and rehabilitation settings. The validity of the DFCS and its sensitivity to low mood was also examined. In this study, correlation analysis was undertaken between DFCS and other existing measures of communication and mood. Assessments took place on local Stroke and Rehabilitation units. Sixteen hospital inpatients with acquired communication problems due to mixed aetiologies were assessed on the DFCS and other measures of communication and mood. Measures used included the DFCS, Frenchay Aphasia Screening Test (FAST), Edinburgh Functional Communication Profile (EFCP), Speech Questionnaire (SQ) and speech and language therapists (SaLT) ratings of global communication ability were used to assess communication. The Visual Analogue Mood Scales (VAMS) and the Stroke Aphasic Depression Questionnaire (SADQ) were administered as measures of low mood. The data indicated that DFCS scores were significantly related to other measures of communication (r = .75-.9, p<.01). Inter-rater reliability was generally good for the DFCS with the exception of the 'understanding' subscale, where a low correlation between staff and SaLT ratings was found. No significant (p>0.05) correlations between DFCS and measures of mood were found. In conclusion, the DFCS may be used for assessing observable communication skills in patients with acquired communication disorders. However, further validation and evaluation of the sensitivity to low mood is required.
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Groves, Adrian R. "Bayesian learning methods for modelling functional MRI". Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:fe46e696-a1a6-4a9d-9dfe-861b05b1ed33.
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Bayesian learning methods are the basis of many powerful analysis techniques in neuroimaging, permitting probabilistic inference on hierarchical, generative models of data. This thesis primarily develops Bayesian analysis techniques for magnetic resonance imaging (MRI), which is a noninvasive neuroimaging tool for probing function, perfusion, and structure in the human brain. The first part of this work fits nonlinear biophysical models to multimodal functional MRI data within a variational Bayes framework. Simultaneously-acquired multimodal data contains mixtures of different signals and therefore may have common noise sources, and a method for automatically modelling this correlation is developed. A Gaussian process prior is also used to allow spatial regularization while simultaneously applying informative priors on model parameters, restricting biophysically-interpretable parameters to reasonable values. The second part introduces a novel data fusion framework for multivariate data analysis which finds a joint decomposition of data across several modalities using a shared loading matrix. Each modality has its own generative model, including separate spatial maps, noise models and sparsity priors. This flexible approach can perform supervised learning by using target variables as a modality. By inferring the data decomposition and multivariate decoding simultaneously, the decoding targets indirectly influence the component shapes and help to preserve useful components. The same framework is used for unsupervised learning by placing independent component analysis (ICA) priors on the spatial maps. Linked ICA is a novel approach developed to jointly decompose multimodal data, and is applied to combined structural and diffusion images across groups of subjects. This allows some of the benefits of tensor ICA and spatially-concatenated ICA to be combined, and allows model comparison between different configurations. This joint decomposition framework is particularly flexible because of its separate generative models for each modality and could potentially improve modelling of functional MRI, magnetoencephalography, and other functional neuroimaging modalities.
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Freeman, Tobe. "Mechanisms of binocular integration and their development in the cat primary visual cortex". Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267925.
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Cetas, Justin Schultz. "Neuronal architecture and functional organization of the rabbit auditory thalamus". Diss., The University of Arizona, 2000. http://hdl.handle.net/10150/284260.
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The ventral division of the medial geniculate body (MGV) is the primary tonotopically-organized nucleus of the auditory thalamus. Previous studies have suggested a close association between the anatomical structure of the MGV and its observed functional organization, but direct correlative studies are lacking. In the present study, regional differences in the cytoarchitecture of the rabbit MGV were described. These different regions were shown to have distinct frequency organizations. The central portion of the rabbit MGV is characterized by a laminated cytoarchitecture that is formed from the orderly arrangement of highly-oriented neuronal cell bodies. In this region, there exists a steep frequency gradient that extends across the dorso-ventral axis of the nucleus, orthogonal to the cellular laminae. This frequency gradient is marked by a discontinuous and stepwise-progression of best frequency. In regions lacking a laminated cytoarchitecture, a steep frequency gradient is absent. In addition, the morphology and basic response properties of individual cells were studied with the juxtacellular labeling technique. Two morphological types of projection neurons as well as two types of putative interneurons were identified on the basis of dendritic thickness, cell soma size and spine morphology. Both types of tufted projection neurons had a variety of different response properties, but the Onset pattern and summation response to binaural stimulation predominate. Quantitative spatial analyses demonstrated that the dendritic fields of both types of tufted neurons are highly oriented. Further, for neurons within the laminated portion of the nucleus, the major axis of orientation of the dendritic fields are parallel to the cellular laminae and orthogonal to the frequency gradient. Departures from this orientation parallel changes in Nissl and functional architecture. A model is presented that correlates the discontinuous and step-wise frequency gradient in the nucleus with the size and morphology of dendritic fields. Lastly, three-dimensional reconstructions of anterogradely-labeled thalamocortical axons reveal a novel class of thalamocortical axon that has collaterals to both layer I as well as layers III/IV of primary auditory cortex; these layers were previously thought to have exclusively separate inputs. This novel class of axon is further evidence for multiple parallel channels from the MGV to AI.