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Moss, Jonathan. "Microcircuitry of the Basal Ganglia." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.514971.
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Drinnan, Suzane Loraine. "G proteins in the basal ganglia." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/28981.
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G proteins are alpha-beta-gamma heterotrimers in the resting state, bound to GDP and complexed with the unbound receptor. Once the receptor becomes occupied, the alpha subunit exchanges GDP for GTP, becomes activated, and dissociates from the receptor and can stimulate or inhibit many intracellular activities such as phosphorylation and channel conductance. For example, Gs and Golf alpha subunits stimulate and Gi alpha subunits inhibit adenylyl cyclase. Go alpha subunits are abundant in brain, but are of unknown function.
cDNAs for the alpha subunit have been cloned. In order to examine the relative distributions of G proteins in the brain, we used in situ hybridization with radiolabelled synthetic oligonucleotide probes. By using a tyrosine hydroxylase antibody, we found that the dopaminergic neurons of the substantia nigra and the noradrenergic neurons of the locus ceruleus express mRNA for the alpha subunits for each of Gi, Go, and Gs. We noted a paucity of Gs mRNA in the striatum. This was surprising because the basal ganglia contain a dopamine-stimulated adenylyl cyclase activity which has been assumed to be transduced by Gs. Also, immunohistochemistry, immunoblotting, and cholera ADP-ribosylation indicated a very high level of Gs alpha-like protein in the striatum. In order to ascertain which specific G protein we were detecting, we made probes to a new G protein previously identified in the olfactory system. Golf is a stimulatory G protein with size and sequence characteristics similar to those of Gs. The cholera toxin ADP-ribosylation site and C-terminal region to which the antibody was made are identical. We made oligonucloetide probes to the translated and untranslated portions of Golf alpha. High levels Golf mRNA and protein were detected in the striatum and nucleus accumbens, in addition to the expected high levels in the olfactory tubercle. Northern blot studies indicated that Golf transcripts are approximately ten-fold more abundant than Gs alpha transcripts in the striatum. These data indicate that Golf in not an olfactory-specific G protein. It is also the major stimulatory G protein in the basal ganglia. The selective expression of high levels of Golf in dopamine-rich forebrain areas suggest that it may couple DI dopamine receptors to adenylyl cyclase. The role of Golf in dopaminergic neurotransmission and neuropsychiatric disease should be considered.Medicine, Faculty of
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Mogoseanu, Diana. "Basal ganglia connections with orofacial muscles." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260710.
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Smith, Denise P. A. "The Basal Ganglia and Sequential Learning." Kent State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1353430597.
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van, Albada Sacha. "Mean-field analysis of basal ganglia and thalamocortical dynamics." Connect to full text, 2008. http://ses.library.usyd.edu.au/handle/2123/5124.
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Thesis (Ph. D.)--University of Sydney, 2009.Includes graphs and tables. Includes list of publications. Title from title screen (viewed June 17, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Physics, Faculty of Science. Degree awarded 2009; thesis submitted 2008. Includes bibliographical references. Also available in print form.
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Church, Andrew John. "Anti-basal ganglia antibodies in movement disorders." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1444607/.
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Sydenham's chorea (SC) is a neurological manifestation following group A Streptococcus infection (GABHS) and has been proposed as an antibody-mediated autoimmune disease. Other movement and psychiatric manifestations following GABHS have been recognised and termed Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). It is proposed that PANDAS may be caused by the same antibody as SC. As the symptoms of PANDAS are identical to Tourette's syndrome (TS), the possibility that TS might turn out to be an autoimmune disorder has implications for the treatment and understanding of these disorders. Evidence of GABHS was found in all patients with SC and PANDAS and 60% of patients with TS. Autoantibodies against basal ganglia (ABGA) were found in all acute SC and PANDAS patients. Only 25% of TS patients were ABGA positive. There was little evidence for ABGA in controls. There was a higher prevalence of ABGA in systemic diseases associated with GABHS but this did not reach significance. ABGA bound to proteins with molecular weights (40, 45, 60 and 98 kDa) and these responses were variably found in SC, PANDAS and TS. The identification of these antigens proved to be problematic due to contamination with other proteins with the same molecular weights. Neurone specific enolase (NSE) was identified as one of the antigens. As this protein was not specific to basal ganglia it cast doubt as to the specificity of ABGA. Interestingly, however, enolase is also found on the surface of GABHS and has extensive homology with human enolase, thus lending support to the possibility of molecular mimicry derived autoimmunity.
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Brown, Jennifer. "Feedback motor control and the basal ganglia." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648678.
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Noy, G. "Abnormal motor behaviour and the basal ganglia." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370974.
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Hutton, Elizabeth Anne May. "Somatosensory cortical input to the basal ganglia." Thesis, University of Edinburgh, 1998. http://webex.lib.ed.ac.uk/abstracts/hutton01.pdf.
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Deus, Yela Juan. "Sistema fronto-basal y aprendizaje incidental." Doctoral thesis, Universitat de Barcelona, 1996. http://hdl.handle.net/10803/670405.
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La memoria no es un proceso unitario. Se han definido diferentes subsistemas mnesicos que operan mediante circuitos neuroanatómicos distintos. Tradicionalmente, los estudios de la memoria se han centrado en el aprendizaje intencionado, especificando que el lóbulo temporal y las estructuras diencefálicas son esenciales para este tipo de memoria. Contrariamente, hay pocos estudios sobre el aprendizaje incidental y no han concretado las estructuras anatómicas implicadas en este aprendizaje. Ya que se considera que este último tipo de aprendizaje es un proceso mnésico automático de adquisición de la información, cabe presuponer la posible implicacion del estriado, de forma similar a lo que ocurre con el sistema motor. Se han seleccionado una muestra de 114 sujetos, 70 como pacientes y 44 pertenecen al grupo control de sujetos sanos. La muestra de pacientes está constituida por sujetos afectos de la enfermedad de Alzheimer (N=20), de la enfermedad de Huntington (N=21), pacientes con calcificaciones bilaterales en los ganglios basales (N=18) y pacientes con una lesión vascular unilateral en el estriado (N=11).
Se ha diseñado una exploración neuropsicológica que ha evaluado funciones cognitivas generales, visoperceptivas y visoespaciales, aprendizaje intencionado, aprendizaje procedimental y funciones frontales en base a pruebas clínicamente estandarizadas. De forma expresa, se han diseñado tareas para evaluar el aprendizaje incidental del espacio, frecuencia y orden temporal. Nuestros resultados sugieren que el aprendizaje incidental puede estar controlado por circuitos frontoneoestriados bilaterales y puede utilizarse como un indicador del funcionamiento mnésico que permita ayudar a discriminar entre la demencia subcortical y cortical, considerando conjuntamente el funcionamiento de la memoria declarativa y procedimental.
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Garas, Farid. "Structural and functional heterogeneity of striatal interneuron populations." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:cfa09ed5-63be-40b4-a974-0f0f0c273656.
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The striatum is the largest nucleus of the basal ganglia, and acts as a point of convergence for thalamic, cortical and midbrain inputs. It is involved in both motor and associative forms of learning, and is composed of spiny projection neurons (SPNs) whose output along the so-called "direct pathway" and "indirect pathway" is modified by the activity of diverse sets of interneurons. Four "classical" or major classes of striatal interneuron can be identified according to the selective expression of the molecular markers parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) or choline acetyltransferase (ChAT). Although the interneurons within a class are generally considered to be homogeneous in form and function, there is emerging evidence that some classes encompass multiple types of neuron, and that the heterogeneity in striatal interneurons extends beyond these four classes. Defining the extent of interneuron heterogeneity is important for understanding how the striatum processes distinct, topographically-organized inputs from the cortex and thalamus in order to govern a wide range of behaviors. To address these issues, a combination of immunofluorescence microscopy and stereological cell counting approaches was used in striatal tissue from rat, mouse and non-human primate. This was supplemented by in vivo recording and juxtacellular labelling of single neurons in rat. A first set of experiments showed that secretagogin (Scgn), a calcium-binding protein, is expressed by a large number of interneurons in the dorsal striatum of rat and primate, but not in the mouse. In all species tested, secretagogin was expressed by a subset of PV+ interneurons and a subset of CR+ interneurons in the dorsal striatum, but also labelled a group of interneurons that did not express any of the classical markers of striatal interneurons. A second set of experiments in the rat demonstrated that the selective co-expression of Scgn by PV+ interneurons delineates two topographically-, physiologically- and morphologically-distinct cell populations. These topographical differences in distribution were largely conserved in the primate caudate/putamen. In rats, PV+/Scgn+ and PV+/Scgn- interneurons differed significantly in their firing rates, firing patterns and phase-locking to cortical oscillations. The axons of PV+/Scgn+ interneurons were more likely to form appositions with the somata of direct pathway SPNs than indirect pathway SPNs, whereas the opposite was true for the axons of PV+/Scgn- interneurons. These two populations of GABAergic interneurons provide a potential substrate through which either of the striatal output pathways can be rapidly and selectively inhibited, and in turn mediate the expression of behavioral routines. A third set of experiments showed that CR+ interneurons of the dorsal striatum can be separated into three populations based on their molecular, topographical and morphological properties. Small-sized ("Type 3") CR+ interneurons co-expressed Scgn and were restricted in their distribution towards the rostro-medial poles of the striatum in both rats and primates. In rats, these neurons also expressed the transcription factor SP8, suggesting that they may be newly generated throughout adulthood. Large-sized, ("Type 1") CR+ interneurons did not express Scgn, but could be further distinguished by their expression of the transcription factor Lhx7. Medium-sized ("Type 2") CR+ interneurons did not express Scgn or Lhx7, and had heterogeneous electrophysiological properties in vivo. The expression of Scgn, but not other classical interneuron markers, identified a group of interneurons that were restricted in their distribution towards the ventro-medial aspects of the dorsal striatum. A fourth set of experiments showed that these neurons are also present in the core and the shell of the nucleus accumbens. Unlike the case of dorsal striatum, however, PV+ interneurons and CR+ interneurons of the nucleus accumbens did not co-express Scgn. Moreover, many of the interneuron populations studied had greater densities in the ventral striatum compared to the dorsal striatum, and had quantifiably strong biases in their distribution towards a variety of axes within both the core and the shell of the nucleus accumbens. These data thus highlight some major differences in the constituent elements of the microcircuits of dorsal striatum and nucleus accumbens. In conclusion, these studies have revealed a great deal of molecular, topographical, electrophysiological and structural heterogeneity within the interneuron populations of the striatum. As several of these interneuron populations were not evenly distributed throughout the striatum, this ultimately suggests that the microcircuit of the striatum is specialized according to regions that differ in their cortical, thalamic and dopaminergic inputs.
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Hallworth, Nicholas E. "Hippocampal theta-related properties of the basal ganglia." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ64958.pdf.
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Kamali, Sarvestani Iman. "Subsystems of the basal ganglia and motor infrastructure." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-136745.
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The motor nervous system is one of the main systems of the body and is our principle means ofbehavior. Some of the most debilitating and wide spread disorders are motor systempathologies. In particular the basal ganglia are complex networks of the brain that control someaspects of movement in all vertebrates. Although these networks have been extensively studied,lack of proper methods to study them on a system level has hindered the process ofunderstanding what they do and how they do it. In order to facilitate this process I have usedcomputational models as an approach that can faithfully take into account many aspects of ahigh dimensional multi faceted system.In order to minimize the complexity of the system, I first took agnathan fish and amphibians asmodeling animals. These animals have rather simple neuronal networks and have been wellstudied so that developing their biologically plausible models is more feasible. I developedmodels of sensory motor transformation centers that are capable of generating basic behaviorsof approach, avoidance and escape. The networks in these models used a similar layeredstructure having a sensory map in one layer and a motor map on other layers. The visualinformation was received as place coded information, but was converted into population codedand ultimately into rate coded signals usable for muscle contractions.In parallel to developing models of visuomotor centers, I developed a novel model of the basalganglia. The model suggests that a subsystem of the basal ganglia is in charge of resolvingconflicts between motor programs suggested by different motor centers in the nervous system.This subsystem that is composed of the subthalamic nucleus and pallidum is called thearbitration system. Another subsystem of the basal ganglia called the extension system which iscomposed of the striatum and pallidum can bias decisions made by an animal towards theactions leading to lower cost and higher outcome by learning to associate proper actions todifferent states. Such states are generally complex states and the novel hypothesis I developedsuggests that the extension system is capable of learning such complex states and linking themto appropriate actions. In this framework, striatal neurons play the role of conjunction (BooleanAND) neurons while pallidal neurons can be envisioned as disjunction (Boolean OR) neurons.In the next set of experiments I tried to take the idea of basal ganglia subsystems to a new levelby dividing the rodent arbitration system into two functional subunits. A rostral group of ratpallidal neurons form dense local inhibition among themselves and even send inhibitoryprojections to the caudal segment. The caudal segment does not project back to its rostralcounterpart, but both segments send inhibitory projections to the output nuclei of the rat basalganglia i.e. the entopeduncular nucleus and substantia nigra. The rostral subsystems is capableof precisely detecting one (or several) components of a rudimentary action and suppress othercomponents. The components that are reinforced are those which lead to rewarding stateswhereas those that are suppressed are those which do not. The hypothesis explains neuronalmechanisms involved in this process and suggests that this subsystem is a means of generatingsimple but precise movements (such as using a single digit) from innate crude actions that theanimal can perform even at birth (such as general movement of the whole limb). In this way, therostral subsystem may play important role in exploration based learning.In an attempt to more precisely describe the relation between the arbitration and extensionsystems, we investigated the effect of dynamic synapses between subthalamic, pallidal andstriatal neurons and output neurons of the basal ganglia. The results imply that output neuronsare sensitive to striatal bursts and pallidal irregular firing. They also suggest that few striatalneurons are enough to fully suppress output neurons. Finally the results show that the globuspallidus exerts its effect on output neurons by direct inhibition rather than indirect influence viathe subthalamic nucleus.QC 20131209
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Marshall, Fiona. "Cholecystokinin/dopamine interactions in the rat basal ganglia." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386170.
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Krosigk, Marcus von. "Information processing in output pathways from basal ganglia." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276840.
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Canavan, A. G. M. "Functions of basal ganglia in man and monkey." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376889.
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Saunders, Arpiar Bruce. "Circuit interactions between the cortex and basal ganglia." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13129563.
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All animals must adapt their behaviors by experience to survive. In mammals, this adaptive process is thought occur through a synaptic loop involving the cortex, basal ganglia (BG) and thalamus. Here we use transgenic mice and novel recombinant viruses (Chapter 1) to explore the brain circuits that underlie this interaction. Our focus is on how cell types within the BG affect cortical feedback during development and in adulthood.
Accepted models postulate that the BG modulate cerebral cortex 1) indirectly via an inhibitory output to thalamus and that this thalamic output is 2) bi-directionally controlled from within the BG by striatal direct (dSPNs) and indirect (iSPNs) pathway spiny neurons. In Chapter 2, we show that activity in iSPNs and dSPNs plays a complementary role in the post-natal synaptic wiring of the BG. Inhibiting iSPNs or dSPNs results in opposite changes in the number of excitatory synapses made onto SPNs from cortical and thalamic inputs. Our results suggest that the cortex-BG-thalamus function in a closed-loop and balanced iSPN/dSPN activity is required for proper synaptic wiring during development.
In Chapter 3, we describe a non-thalamic output of the BG to the frontal cortex (FC) emanating from globus pallidus externus (GP). The GP-FC projection consists of two cell types that release GABA and GABA/Acetylcholine, mostly onto cortical interneurons, with the net effect of increasing cortical firing rate. These results suggest that iSPNs and dSPNs can affect cortical output through GP-based disinhibition in addition to thalamus-based excitation. Moreover, GP-FC cells provide a pathway by which drugs that target dopamine receptors for the treatment of neuropsychiatric disorders can act in the BG yet modulate activity in FC. The presence of a direct BG output to cortex extends the looped architecture through which the cortex-BG-thalamus control adaptive behavior and can become dysregulated to cause disease. Together our thesis results support the phenomenology of the BG pathway model, but suggest a major revision to the underlying circuitry.
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Simpson, Carol S. "Regulation of gene expression in the basal ganglia." Thesis, University of Glasgow, 1995. http://theses.gla.ac.uk/38912/.
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Enkephalin gene expression is modulated by the dopaminergic system in the rat striatum. Intraperitoneal administration of the typical neuroleptic drugs haloperidol (1mg/kg) and fluphenazine (3mg/kg) significantly increase levels of proenkephalin mRNA in the caudal striatum compared to saline treated controls, although the atypical neuroleptic drug clozapine (3mg/kg) has no effect on the levels of proenkephalin mRNA in the rat. Methiothepin (10mg/kg), an antipsychotic with the ability to antagonise both serotonin and dopamine receptors, can also induce proenkephalin mRNA levels in rat striatum. This induction is observed twenty-four hours after the drugs are given. Tachykinin gene expression is modulated by the dopaminergic system in the rat striatum. Intraperitoneal administration of the typical neuroleptic drugs haloperidol (1mg/kg) and fluphenazine (3mg/kg) significantly reduce the levels of preprotachykinin mRNA in the rat striatum, compared to saline treated controls. This effect is observed twenty-four hours after drug administration. The atypical neuroleptic drug clozapine (3mg/kg) and the antipsychotic methiothepin (10mg/kg) have no significant effect on the levels of preprotachykinin mRNA in the rat striatum. Somatostatin gene expression in the rat striatum is significantly increased by low doses of the atypical neuroleptic drug clozapine (3mg/kg) and by the antipsychotic drug methiothepin (10mg/kg), after acute administration. Acute treatment with typical neuroleptics has no effect in the rat striatum.
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Eddy, Clare Margaret. "Social cognition in disorders of the basal ganglia." Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/366/.
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Patients with disorders of the basal ganglia, such as Parkinson’s disease, Huntington’s disease and Tourette’s Syndrome, exhibit characteristic motor symptoms and less obvious cognitive deficits. These deficits can be understood with reference to the model of cortico-striato-thalamo-cortical circuitry proposed by Alexander et al. (1986) which highlights how the basal ganglia can affect the functioning of the whole of the frontal lobe. This thesis explored the possibility that patients with these disorders also have difficulties with social cognition. Patients with Parkinson’s exhibited deficits in reasoning about mental states. These deficits can largely be attributed to executive dysfunction which results from disordered activity in the circuitry linking the dorsolateral prefrontal cortex and the basal ganglia. Patients with Huntington’s exhibited reduced fear responses which most likely results from abnormal amygdala activity. Patients with Tourette’s exhibited deficits on a wide range of social cognitive tasks involving reasoning about mental states, non-literal language interpretation and economic decision making. These difficulties probably reflect dysfunction in circuitry linking the anterior cingulate and insula with the basal ganglia. These studies offer insight into the neuroanatomical basis of the behavioural symptoms associated with these conditions whilst highlighting the necessity to develop more precise and inclusive models of frontostriatal circuitry.
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Chan, Shiao-hui. "Linguistic Sequencing in the Cortex and Basal Ganglia." Diss., The University of Arizona, 2007. http://hdl.handle.net/10150/195441.
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Due to the common belief that language is unique to humans, great emphasis has been placed on the neocortex, while the role of the subcortical areas has been minimized. This project used event-related functional magnetic resonance imaging (fMRI) to study the linguistic involvement of the basal ganglia (BG). Previous research has demonstrated that the BG are implicated in building up sequences of behavior into meaningful, goal-directed repertoires This study developed the idea of motor sequencing into linguistic sequencing to test the BG's involvement in the abstract sequencing of language. Since past imaging studies failed to present a coherent picture of the BG laterality, which might be due to the absence of the control for subjects' familial handedness background, this subject factor was also investigated.Twenty-four right-handed, neurologically healthy English speakers were recruited. Half of them had left-handed blood relatives (FS+); the other half did not (FS-). Their tasks included 1) linguistic sequencing--reordering phrases into a sentence or reordering words along the general-specific dimension, 2) non-linguistic sequencing--swapping designated phrases/words and 3) repeat--repeating words in their original sequence. Voxel-wise analysis showed that both the BG and cortical areas were activated when subjects performed a reordering task. Region of interest (ROI) analysis demonstrated that the BG were involved in linguistic sequencing (reorder - repeat) and that Broca's area and the caudate head were co-opted in computing hierarchical structure (reorder - swap). Although familial sinistrality did not alter the activation pattern of Broca's area and the caudate head, it played a role in their activation asymmetry: both subject groups had left-lateralization in the inferior frontal gyrus, but they failed to show identical laterality in the BG. A possible explanation based on the direct and indirect pathways in the BG was offered and the laterality discrepancy was attributed to these two groups' different time course of language acquisition.To summarize, this study suggested that the BG, especially the head of the caudate nucleus, were involved in the abstract sequencing of language and that the distinct brain asymmetry associated with different familial sinistrality background might be rooted in the BG.
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Ng, Kwok Yan. "Localization of GABA receptors in the rat basal ganglia." HKBU Institutional Repository, 2003. http://repository.hkbu.edu.hk/etd_ra/421.
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Søiland, Stian. "Sequence learning in a model of the basal ganglia." Thesis, Norwegian University of Science and Technology, Department of Computer and Information Science, 2006. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-9312.
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This thesis presents a computational model of the basal ganglia that is able to learn sequences and perform action selection. The basal ganglia is a set of structures in the human brain involved in everything from action selection to reinforcement learning, inspiring research in psychology, neuroscience and computer science. Two temporal difference models of the basal ganglia based on previous work have been reimplemented. Several experiments and analyses help understand and describe the original works. This uncovered flaws and problems that is addressed.
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van, Albada Sacha Jennifer. "Mean-field analysis of basal ganglia and thalamocortical dynamics." University of Sydney, 2009. http://hdl.handle.net/2123/5124.
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PhDWhen modeling a system as complex as the brain, considerable simplifications are inevitable. The nature of these simplifications depends on the available experimental evidence, and the desired form of model predictions. A focus on the former often inspires models of networks of individual neurons, since properties of single cells are more easily measured than those of entire populations. However, if the goal is to describe the processes responsible for the electroencephalogram (EEG), such models can become unmanageable due to the large numbers of neurons involved. Mean-field models in which assemblies of neurons are represented by their average properties allow activity underlying the EEG to be captured in a tractable manner. The starting point of the results presented here is a recent physiologically-based mean-field model of the corticothalamic system, which includes populations of excitatory and inhibitory cortical neurons, and an excitatory population representing the thalamic relay nuclei, reciprocally connected with the cortex and the inhibitory thalamic reticular nucleus. The average firing rates of these populations depend nonlinearly on their membrane potentials, which are determined by afferent inputs after axonal propagation and dendritic and synaptic delays. It has been found that neuronal activity spreads in an approximately wavelike fashion across the cortex, which is modeled as a two-dimensional surface. On the basis of the literature, the EEG signal is assumed to be roughly proportional to the activity of cortical excitatory neurons, allowing physiological parameters to be extracted by inverse modeling of empirical EEG spectra. One objective of the present work is to characterize the statistical distributions of fitted model parameters in the healthy population. Variability of model parameters within and between individuals is assessed over time scales of minutes to more than a year, and compared with the variability of classical quantitative EEG (qEEG) parameters. These parameters are generally not normally distributed, and transformations toward the normal distribution are often used to facilitate statistical analysis. However, no single optimal transformation exists to render data distributions approximately normal. A uniformly applicable solution that not only yields data following the normal distribution as closely as possible, but also increases test-retest reliability, is described in Chapter 2. Specialized versions of this transformation have been known for some time in the statistical literature, but it has not previously found its way to the empirical sciences. Chapter 3 contains the study of intra-individual and inter-individual variability in model parameters, also providing a comparison of test-retest reliability with that of commonly used EEG spectral measures such as band powers and the frequency of the alpha peak. It is found that the combined model parameters provide a reliable characterization of an individual's EEG spectrum, where some parameters are more informative than others. Classical quantitative EEG measures are found to be somewhat more reproducible than model parameters. However, the latter have the advantage of providing direct connections with the underlying physiology. In addition, model parameters are complementary to classical measures in that they capture more information about spectral structure. Another conclusion from this work was that a few minutes of alert eyes-closed EEG already contain most of the individual variability likely to occur in this state on the scale of years. In Chapter 4, age trends in model parameters are investigated for a large sample of healthy subjects aged 6-86 years. Sex differences in parameter distributions and trends are considered in three age ranges, and related to the relevant literature. We also look at changes in inter-individual variance across age, and find that subjects are in many respects maximally different around adolescence. This study forms the basis for prospective comparisons with age trends in evoked response potentials (ERPs) and alpha peak morphology, besides providing a standard for the assessment of clinical data. It is the first study to report physiologically-based parameters for such a large sample of EEG data. The second main thrust of this work is toward incorporating the thalamocortical system and the basal ganglia in a unified framework. The basal ganglia are a group of gray matter structures reciprocally connected with the thalamus and cortex, both significantly influencing, and influenced by, their activity. Abnormalities in the basal ganglia are associated with various disorders, including schizophrenia, Huntington's disease, and Parkinson's disease. A model of the basal ganglia-thalamocortical system is presented in Chapter 5, and used to investigate changes in average firing rates often measured in parkinsonian patients and animal models of Parkinson's disease. Modeling results support the hypothesis that two pathways through the basal ganglia (the so-called direct and indirect pathways) are differentially affected by the dopamine depletion that is the hallmark of Parkinson's disease. However, alterations in other components of the system are also suggested by matching model predictions to experimental data. The dynamics of the model are explored in detail in Chapter 6. Electrophysiological aspects of Parkinson's disease include frequency reduction of the alpha peak, increased relative power at lower frequencies, and abnormal synchronized fluctuations in firing rates. It is shown that the same parameter variations that reproduce realistic changes in mean firing rates can also account for EEG frequency reduction by increasing the strength of the indirect pathway, which exerts an inhibitory effect on the cortex. Furthermore, even more strongly connected subcircuits in the indirect pathway can sustain limit cycle oscillations around 5 Hz, in accord with oscillations at this frequency often observed in tremulous patients. Additionally, oscillations around 20 Hz that are normally present in corticothalamic circuits can spread to the basal ganglia when both corticothalamic and indirect circuits have large gains. The model also accounts for changes in the responsiveness of the components of the basal ganglia-thalamocortical system, and increased synchronization upon dopamine depletion, which plausibly reflect the loss of specificity of neuronal signaling pathways in the parkinsonian basal ganglia. Thus, a parsimonious explanation is provided for many electrophysiological correlates of Parkinson's disease using a single set of parameter changes with respect to the healthy state. Overall, we conclude that mean-field models of brain electrophysiology possess a versatility that allows them to be usefully applied in a variety of scenarios. Such models allow information about underlying physiology to be extracted from the experimental EEG, complementing traditional measures that may be more statistically robust but do not provide a direct link with physiology. Furthermore, there is ample opportunity for future developments, extending the basic model to encompass different neuronal systems, connections, and mechanisms. The basal ganglia are an important addition, not only leading to unified explanations for many hitherto disparate phenomena, but also contributing to the validation of this form of modeling.
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Khorram, Babak. "Functionally relevant basal ganglia subdivisions in first-episode schizophrenia." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/412.
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Schizophrenia is among the most debilitating mental disorders, yet the pathophysiology remains unclear. The basal ganglia, a region of the brain involved in motor, cognitive, and sensory processes, may be involved in the pathophysiology of schizophrenia. Some, but not all, neuroimaging studies suggest abnormalities of the basal ganglia in schizophrenia. However, previous studies have examined whole basal ganglia nuclei as opposed to using a unified basal ganglia complex that incorporates anterior-posterior divisions, dorsal-ventral divisions, and gray-white matter segmentation. The hypothesis for the present study was that basal ganglia sub-regions forming functionally relevant subdivisions might be different in schizophrenia. Magnetic resonance imaging scans were acquired from 25 first-episode schizophrenia subjects and 24 healthy subjects. Using manual and automated neuroimaging techniques, total and segmented (gray-white matter) volumes were obtained for the caudate, putamen, and globus pallidus. For the striatum (caudate and putamen), total and segmented volumes were obtained for their respective sub-regions. These sub-regions were restructured into associative, limbic, and sensorimotor subdivisions. Schizophrenia subjects had 6% smaller gray matter volumes for the caudate and 8% smaller gray matter volumes for the associative striatum relative to healthy subjects. Basal ganglia function was studied by examining performance on a neuropsychological test that assesses frontostriatal functioning. For male subjects there was a significant negative correlation between volume of the associative striatum and performance on the neuropsychological test (r=-0.57, p=0.03). Smaller volumes of the associative striatum were associated with more errors on the neuropsychological test. This test was specific to the associative striatum, as another neuropsychological test did not reveal any correlation. In schizophrenia subjects, the relationship between basal ganglia volumes and motor symptoms severity was examined. For antipsychotic-naive subjects there was a significant negative correlation between volume of the motor striatum and severity of Parkinsonism (r=-0.65, p=0.03). The present study suggests that total basal ganglia nuclei volumes are not different in schizophrenia, but gray matter volumes of total basal ganglia nuclei and subdivisions forming functional units may be different in schizophrenia. Structural abnormalities involving the basal ganglia may lead to disrupted functional circuits in schizophrenia.
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Huang, Zhuo. "Properties of NMDA receptors in the rat basal ganglia." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1443978/.
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Native subtypes of NMDA receptors with distinct developmental and anatomical distribution are present in the brain. Knowledge of their function and pharmacology greatly helps in understanding the involvement of NMDA receptors in physiological and pathological processes in the central nervous system. Multiple patch-clamping methods were carried out in my experiments. First, the single-channel properties of native NMDA receptors were studied in outside-out patches excised from neuronal cell bodies in substantia nigra pars compacta (SNc) and subthalamic nucleus (STN) from 7-day old rats. The steady state channel activations produced by NMDA (100 nM or 200 uM) and glycine (10 uM) were studied at -60 mV. The results showed that both large and small conductance channels are present on STN and SNc neurons. These large conductance NMDA channels from SNc and STN display a high ifenprodil sensitivity, suggesting NR2B-containing NMDA receptors are present on SNc and STN neurons. In addition, direct transition analysis suggests that the small conductance channels may be due to NR2D-containing NMDA receptors. Second, whole-cell patch-clamp recording of bath application-induced NMDA receptor-mediated currents (Inmda) in dopaminergic neurons of SNc in brain slices from P7 rats was used to characterize the ifenprodil inhibition and voltage-dependence of Mg2+ block of NMDA receptors. The NMDA-induced whole-cell currents were evoked by NMDA (10 uM or 200 uM) and glycine (10 pM). There are two main findings from the whole-cell experiments. (1) The NMDA-induced whole-cell currents display a high ifenprodil sensitivity, suggesting the presence of NR2B-containing NMDA receptors on P7 rat SNc neurons. (2) The combined application of Mg2+ and ifenprodil reduced the voltage-dependent Mg2+ block, which is consistent with recombinant NR2D-containing NMDA receptors that have a lower affinity for Mg2+. This suggests that NR2D-containing NMDA receptors are present in P7 rat SNc. Third, in order to evaluate the deactivation kinetics of extrasynaptic NMDARs, outside-out patches containing multiple channels were obtained from P7 rat dopaminergic neurons of SNc and stimulated with a brief synaptic-like (l-4ms) pulse of ImM glutamate. The results suggested that the triheteromeric NR1-NR2B-NR2D rather than diheteromeric NR1-NR2D NMDA receptors are present on extrasynaptic sites of SNc neurons. In addition, in order to investigate voltage-dependent Mg2+ block and memantine block, several channel block models were developed to evaluate multiple Mg2+ effects on native NMDA receptors and competition between Mg2+ and memantine for block of NMDAR channels.
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Abualait, Turki S. Sabrah. "Investigating basal ganglia function using ultra-high field MRI." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/32366/.
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The basal ganglia (BG) are a group of highly interconnected nuclei that are located deep at the base of the cerebral cortex. They participate in multiple neural circuits or 'loops' with cognitive and motor areas of the cerebral cortex. The basal ganglia has primarily been thought to be involved in motor control and learning, but more recently a number of brain imaging studies have shown that the basal ganglia are involved also in cognitive function. The aim of this work is to investigate the role of the basal ganglia in cognitive control and motor learning by examining its involvement in GO/WAIT and GO/NO-GO tasks, and Motor Prediction task, respectively. Ultra-high field (7 Tesla) fMRI is used to provide higher BOLD contrast and thus higher achievable spatial resolution. A dual echo gradient echo EPI method is used to obtain high quality images from both cortical and sub-cortical regions. A common neural basis across different forms of response inhibition using GO/WAIT and GO/NO-GO cognitive paradigms is observed in the experiments of Chapter 4, as well as distinct brain regions involved in withholding and cancelling of motor responses. Using the GO/WAIT cognitive paradigm in Chapter 5 individuals with Tourette syndrome (TS) are compared to age and gender-matched control healthy subjects (CS), and it is shown that TS subjects are unable to recruit critical cortical and sub-cortical nodes that are typically involved in mediating behavioural inhibition. Furthermore, in Chapter 6, the role of the basal ganglia in motor learning is investigated using the Motor Prediction task. The findings show that the basal ganglia and midbrain regions (i.e., habenula) are involved in motor prediction and enhancing the reinforcement learning process. This thesis aims to investigate the basal ganglia function in cognitive and motor tasks, and concludes with suggested further studies to advance our understanding of the role of the basal ganglia nuclei in cognitive function.
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Inoue, Manabu. "Sensory stimulation accelerates dopamine release in the basal ganglia." Kyoto University, 2006. http://hdl.handle.net/2433/144317.
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Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第11982号
医博第2926号
新制||医||912(附属図書館)
23795
UT51-2006-C662
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 髙橋 良輔, 教授 金子 武嗣, 教授 大森 治紀
学位規則第4条第1項該当
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Morari, Michele. "Physiopathological aspects of NMDA transmission in the basal ganglia : in vitro and in vivo release studies /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3347-2.
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Booth, Philip Anthony Chesworth. "Studies on the pallidostriatal and pallidosubthalmic pathways." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249380.
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Shin, SooYoon. "Role of the primate basal ganglia in saccadic eye movements." UNIVERSITY OF PITTSBURGH, 2012. http://pqdtopen.proquest.com/#viewpdf?dispub=3485870.
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Augood, Sarah Jane. "Chemical signalling in the basal ganglia : manipulation of dopamine neurotransmission." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304190.
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The role of endogenous dopamine in mediating striatal preproenkephalin A, proneurotensin and preprosomatostatin gene expression in vivo was studied in monkeys treated with the catecholamine neurotoxin MPTP, and in rats treated acutely with selective dopamine D1 and D2 receptor antagonists. The effect on striatal neuropeptide gene expression were assessed by in situ hybridisation. The effect of MPTP treatment on the striatal content of substance P-like immunoreactivity was also studied by quantitative immunocytochemistry. Chronic MPTP treatment resulted in a significant loss (> 90&37) of tyrosine hydroxylase mRNA-containing cells in the ipsilateral substantia nigra pars compacta and ventral tegmental area; an increase in preproenkephalin A gene expression; and a decrease in the tissue content of substance P-like immunoreactivity in the ipsilateral striatum. Selective blockade of D2 receptors in rats also resulted in an increase in preproenkephalin A gene expression, whereas blockade of D1 receptors reduced expression of this gene, hence it appears that the dominant action of endogenous dopamine on preproenkephalin gene expression is via D2 receptors. Acute dopamine receptor blockade has different effects on other peptide genes in the striatum: proneurotensin gene expression was activated following D2 but not D1 receptor blockade, while preprosomatostatin gene expression was attenuated following blockade of either receptor subtype. The coupling of receptor activation to gene expression was studied by treatment of rats with pertussis toxin, which irreversibly ribosylates membrane Gi/o proteins. Microinjection of pertussis toxin into the striatum led to an increase in expression of both proneurotensin and preproenkephalin A genes, consistent with the hypothesis that Gi/o proteins mediate the effects of D2 receptor activation on striatal enkephalin and neurotensin cells.
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Shaunak, Sandip. "Frontal lobe and basal ganglia control of saccadic eye movements." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299858.
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Chatha, B. Tracey. "Localization of excitatory amino acid receptors in the basal ganglia." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365693.
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Lacey, Carolyn Jane. "The neural networks interconnecting the basal ganglia and the thalamus." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437355.
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Morris, Laurel Sophia. "Cortical-basal ganglia circuits : control of behaviour and alcohol misuse." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/268015.
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Highly organised and differentiated neural circuits form and unite to link the cortex with the basal ganglia and thalamus to mediate movement, cognition and behaviour. Previous assertions that the basal ganglia primarily acted to filter cortical information to facilitate motor outputs only have since given way to an understanding of the basal ganglia as a relay and gating structure with functionally and structurally segregated inputs, functions and outputs. Thus, cortical – basal ganglia circuits can be segregated into three broadly separable functional domains mediating motor (primary and supplementary motor cortex (SMA) and putamen), cognitive (dorsolateral prefrontal cortex (dlPFC) and caudate), and limbic (ventromedial prefrontal cortex and ventral striatum (VS)) processes. In addition, cognitive and behavioural programs that pass through the cortical – basal ganglia circuitry can be subject to filtering by the subthalamic nucleus (STN), which receives direct projections from the cortex. This work first demonstrated the functional organisation of segregated intrinsic cortical – basal ganglia circuits in humans, alongside a detailed map of functional subzones within STN, a small and technically inaccessible midbrain structure. The behavioural relevance of the defined cortical – basal ganglia circuits was investigated by examining the cognitive constructs of impulsivity and compulsivity. Waiting impulsivity, a tendency towards rapid premature responses that has been associated with compulsive drug use, was associated with connectivity between limbic regions including subgenual anterior cingulate cortex, VS and STN. However, motor impulsivity, in the form of stopping ability, was associated with motoric regions including pre-SMA and STN. Compulsivity was captured as deficits in: reversal learning, implicating lateral orbitofrontal cortex; attentional shifting, implicating dlPFC; and habit learning, implicating SMA. Neural circuit changes were also examined in individuals with alcohol dependence and binge drinkers. Waiting impulsivity was elevated in both groups and the functional connectivity, microstructural integrity and anatomical connectivity of the neural circuit underlying waiting impulsivity were associated with problematic drinking behaviours in both groups. Together, this work establishes that discrete functional subzones of small subcortical regions can be differentiated in humans and that their behavioural correlates can be similarly mapped. The definition of intrinsic network architecture underlying a particular behaviour and the demonstration its disturbance in psychiatric groups will crucially inform the development of future diagnostic and therapeutic models.
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Nastuk, Mary Alden. "Muscarinic cholinergic receptors in the developing and mature basal ganglia." Thesis, Massachusetts Institute of Technology, 1988. http://hdl.handle.net/1721.1/14601.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 1988.Title as it appeared in M.I.T. Graduate List, June 1988: Muscarinic cholinergic binding sites in the developing and mature basal ganglia.
Includes bibliographical references.
by Mary Alden Nastuk.
Ph.D.
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Flaherty, Alice Weaver. "Multiple stages of sensorimotor processing in the primate basal ganglia." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/12884.
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Gillies, Andrew J. "The role of the subthalamic nucleus in the basal ganglia." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/522.
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The basal ganglia are a collection of interconnected subcortical nuclei which have been implicated inmotor, cognitive and limbic functions. The subthalamic nucleus is the sole excitatory structure within the basal ganglia. Given its central position influencingmany basal ganglia nuclei, it is likely to play an important role in the processing that is performed by the basal ganglia. In this thesis a theoretical analysis of the subthalamic nucleus is presented. In order to explore the multiple facets of processing that may be occurring, models that are designed to capture aspects of the subthalamic nucleus at different levels are developed. These include anatomical, network processing and single neuron multi–compartmental models. Through the integration of the results obtained from these models a new and coherent view of the processing of the subthalamic nucleus is presented. It is predicted that the subthalamic nucleus be considered as a massively connected excitatory network. Two distinct modes of asymptotic behaviour exist in such a network: a low resting state and a high self–sustained state. The single neuron multi– compartmental model demonstrates that the calcium T–type channel is the primary determinant of characteristic neuron behaviour. Such behaviour includes a slowaction potential, initial spike clustering, and a post-response quiescence. The network and single neuron results taken togetherprovide an intrinsicmechanismfor termination of uniform high activity generated by the excitatory network. It is therefore predicted that large regions of the subthalamic nucleus respond uniformly to stimuli, in the form of a pulse of activity with a sharp rise and fall. In addition, the single neuron model indicates that pulses will occur in pairs. It is proposedthat the subthalamic nucleus acts as a “braking mechanism”. It can induce, via intermediate structures, awide-spread pulse of inhibition on basal ganglia target nuclei. Furthermore, the sequence of two pulses can generate a window of disinhibition over the basal ganglia targets. The width of this time window may be under direct striatal control. Variable interpulse duration implies a role for the subthalamic nucleus in temporal processing.
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Clinch, Susanne. "Developing and evaluating behavioural tasks to assess basal ganglia function." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/100957/.
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Huntington’s disease (HD) is a primary example of a basal ganglia disorder, from which, medium spiny neurons in the striatum degenerate. As this causes a breakdown in basal ganglia cortico-thalamic circuitry, this leads to a range of symptoms including motor, cognitive and behavioural deficits. One therapeutic option is to replace medium spiny neurons with precursor striatal cells and reconnect the lost circuitry. However, the lack of performance based functional outcome measures for people with HD have made it difficult to assess how the graft affects standards of daily living. Although neuroimaging techniques can be used to quantify the morphological and molecular effects that the intervention has on that brain region, and associated circuitry, an important question still remains, namely whether there has been any effect on functional ability. Using assessments that have high ecological validity, such as dual tasks could be a valuable measure, especially as previous studies suggest that the striatum is required for optimal performance in such tasks. Therefore the focus of this thesis was to design, develop and assess performance based functional tasks that involve the neurocircuity affected in HD; namely the basal ganglia. The aim of the study in Chapter 2 was to select, develop and evaluate motor-cognitive dual task paradigms for use in people with HD. The findings revealed that the Step and Stroop which targeted lower limb function, best distinguished disease stage in HD compared to the other lower limb assessments tested. During this experiment, it became apparent that upper limb assessments for people with HD were particularly limited. Therefore, in Part 2, a new upper limb dual task assessment was developed and called the Clinch token transfer test (C3t). The findings revealed that this was sensitive to disease stage and could provide a useful outcome measure for people with HD in the future. To take the findings from Chapter 2 further, a new, standardised C3t was developed. This version was evaluated, optimised, and then validated in a large group of people gene positive for HD, and in heathy controls. The findings revealed that the C3t significantly correlated with all the Unified Huntington Disease Rating Scale measures, successfully distinguished between all disease stages, and revealed that the performance in this task was also sensitive to the subtle disease symptoms in the early stages of HD. As the Stroop task is commonly used in people with HD, the aim of Chapter 3 was to use immediate early gene expression to identify if the striatum was activated during a rodent analogue of the Stroop task. The findings revealed what could be the first in a series of experiments in that, striatal activation significantly correlated with performance in the congruent and the incongruent versions of this test when compared to cage controls. The findings presented in this thesis support that dual task assessments could have an important role in assessing function in HD, which could translate to performance in tasks that affect the standards of daily living. Importantly, as different dual tasks can result in different levels of dual task interference, this suggests that practice effects could affect how sensitive some dual task paradigms are over others. In addition, selecting outcome measures that are specific to the regions affected in HD, in both clinic and in pre-clinical models, will permit sensitive tracking of neurodegeneration, and could also be used to assess the outcomes of therapies that target this specific neural region.
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Tinterri, Andrea. "From fate specification to circuit formation within the basal ganglia." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066576/document.
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Les ganglions de la base (BG) sont un ensemble de noyaux qui contrôle des taches fondamentales de la vie quotidienne, notamment le control des mouvements, ainsi que l’apprentissage et le reward. En particulier, le striatum est le noyau principal des BG et le majeur relais d’input. Il est formé par deux sous-types de neurones de projection (SPN) qui modulent l’activité de sortie des BG directement (dSPN) ou indirectement (iSPN) via d’autres structures. Les deux populations sont intermelangés, ce qui permet l’activation parallèle des deux voies. Une perte d’équilibre entre l’activité des dSPN et des iSPN est partie de l’étiologie de plusieurs neuropathies des BG, y compris la maladie de Parkinson et celle de Huntington. Malgré l’importance fonctionnelle de ces neurones, on a une connaissance très incomplète de comment les deux sous-types sont spécifiés au cours du développement; de plus, la question de comment les deux sous-types se mélangent pour former l’architecture fonctionnelle du striatum reste à élucider. Utilisant une combinaison unique d’outils génétiques disponible dans la souris, j’ai montré que les dSPN et iSPN sont spécifiés dés très tôt et diffèrent dans leur distribution dans le striatum embryonnaire pour s’intermélanger progressivement. De plus, je montre que ce processus de mélange repose sur l’expression du facteur de transcription Ebf1, un gène qui est exprimé spécifiquement dans le dSPN et contrôle aussi l’intégration de ces derniers dans les circuits des BG. Mes résultats fournissent un nouveau contexte pour investiguer les mécanismes moléculaires qui contrôlent l’assemblage du striatum et donnent des informations essentielles pour la génération de neurones striataux in vitro. Une autre population des BG, les neurones du corridor, ont la même origine que les SPN; cependant, au lieu de migrer vers le striatum, ces neurones forment une structure provisoire qui est cruciale pour former la capsule interne, un des majeurs faisceaux d’axones dans le cerveau des mammifères. Malgré leur importance pour le développement de la connectivité cérébrale, on ne sait pas si ces neurones jouent aussi un rôle dans le cerveaux adulte. À travers une combinaison de fate mapping génétique et d’analyse moléculaire à différent stades du développement, je montre que ces neurones contribuent à des noyaux spécifiques de l’amygdale étendue, une structure impliquée dans le control de la peur et de l’anxiété. Ces résultats montrent que les neurones du corridor pourraient contribuer à la régulation de l’anxiété et améliorent notre connaissance sur la formation de ces structures, qui sont très conservés au cours de l’évolution et qui ont un grand intérêt pathologique. Pris dans l’ensemble, mes résultats fournissent non seulement des nouvelles et très importantes informations sur la façon dont les circuits des BG sont formés, mais déterminent un nouveau cadre conceptuel pour investiguer le développement et la connectivité du cerveau antérieurBasal ganglia (BG) are a set of brain nuclei that control crucial aspects of everyday life such as motor control, habit learning and reward. In particular, the striatum is the biggest nucleus and input station of BG. It is formed by two subsets of projection neurons (SPN) that modulate BG output activity either directly (dSPN) or indirectly via other BG structures (iSPN). The two populations are intermixed, allowing parallel activation of the two pathways. Impaired balance of dSPN and iSPN activity is part of the aetiology of many BG neuropathies, including Parkinson’s and Huntington’s diseases; however, to date we have poor knowledge on how the two subtypes are specified and how they intermix during development. Using a unique combination of mouse genetic tools, here I show that dSPN and iSPN are specified early as independent populations, have different early distribution and gradually intermix. Moreover, I show that the process of intermix relies on expression of transcription factor Ebf1 in dSPN, a gene that also controls dSPN ability to integrate in BG circuits. These findings provide a new framework to investigate the molecular mechanisms controlling striatal mosaic assembly and will provide instrumental to generate fully formed striatal neurons in vitro. Another BG population, corridor neurons, shares common origin with SPN; however, instead of migrating toward the striatum, these cells form a transient corridor (Co) that is crucial for the formation of the internal capsule, a major axonal pathway in mammals. Despite their importance for brain wiring, whether Co cells also play a role in the adult brain is unknown. Through a combination of genetic fate map and in vivo timecourse, I surprisingly show that these cells participate to specific nuclei of the central extended amygdala, a structure implicated in anxiety and fear response. This finding indicates that Co neurons might contribute to anxiety regulation and sheds new light on the formation of evolutionarily conserved structures of great behavioral and clinical interest. Taken together, my findings not only provide new and critical information on neuronal migration and circuit formation in the BG, but also a new conceptual framework to investigate the formation of nuclear structures of the anterior brain
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Furuta, Takahiro. "A novel modulatory system in the cortico-basal-ganglia loop." 京都大学 (Kyoto University), 2003. http://hdl.handle.net/2433/149163.
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Connell, Timothy M. "The role of the basal ganglia in cognition and language." Title page, contents and abstract only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phc75235.pdf.
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Bibliography: p. 379-435. A thesis which aims to clarify the role of the basal ganglia in higher mental processes by investigating the role of the dorsolateral prefrontal circuit, the lateral orbital frontal circuit and the anterior cingulate circuit and other language related circuitry. Twenty five right-handed people with verified lesions of this circuitry were tested for attention, perfomance of complex motor programs, executive functions, memory and language skills and compared to a control group. It was found that mental processing associated with the basal cortical circuitry was orchestration of subprocesses (at the cortical level) and their integration (at the subcortical level) to enable their fluid and effective synchronization for the person to complete more complex tasks.
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Canudas, Teixidó Anna-Maria. "Estudi de la degeneració transneuronal en models de malalties que afecten als ganglis basals." Doctoral thesis, Universitat de Barcelona, 2001. http://hdl.handle.net/10803/672867.
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L'objectiu general d'aquest treball és aprofundir en l'estudi de la fisiopatologia de les malalties degeneratives, un dels objectius principals per a la farmacologia actual degut a l'increment de la seva incidència en les últimes dècades.
Mitjançant la utilització de models experimentals d 'aquestes patologies s'han plantejat diferents objectius més concrets:
A.- Induir la malaltia de Parkinson experimental a través de la injecció de l'MPP+ en la substància negra de rata.
A1.-Estudiar la resposta glial en el nucli estriat després de La degeneració anterograda de les neurones dopaminèrgiques causada per la injecció de l'MPP+ en la substància negra. Implicació en el mecanisme de mort neuronal i de regeneració.
B.- Induir la malaltia de Huntington experimental a través de la injecció d'aminoàcids excitadors en el nucli estriat de rata.
B1.-Caracteritzar la resposta endògena tròfica a l'excitotoxicitat, valorant els canvis en l 'expressió del BDNF i l'NT-3 així com la dels seus receptors, TrkB i TrkC, en l'escorça cerebral després de la injecció de diferents agonistes del receptor del glutamat en el nucli estriat.
B2.-Estudiar la regulació endògena dels nivells de BDNF en Ja substància negra de rata després de la lesió estriatal induïda per l'àcid kaínic, així com la possible implicació d'aquesta neurotrofina en la supervivència de les neurones de la substància negra front la lesió excitotòxica en el nucli estriat.
3. Estudiar el possible efecte neuroprotector de les neurotrofines BDNF, NT-3 iNT-4/5, sobre les diferents poblacions neuronals de projecció del nucli estriat, en el model excitotòxic de l'àcid quinolínic. Es van implantar en l 'estriat de rata adulta línies cel·lulars establertes que secreten alts nivells de BDNF, NT-3 i NT-4/5 recombinant abans de la injecció de l'aminoàcid excitador.
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Larsen, Tobias. "The Role of Basal Ganglia in Decision Making and Reinforcement Learning." Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.520597.
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Hayes, Lauren Mary. "Subcortical loops through the basal ganglia are organised into segregated channels." Thesis, University of Sheffield, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548391.
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Burgess, Jonathan G. "Identifying tremor-related characteristics of basal ganglia nuclei in Parkinson's disease." Thesis, University of Reading, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.541954.
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Sharott, Andrew David. "The role of oscillation population activity in cortico-basal ganglia circuits." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445058/.
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The basal ganglia (BG) are a group of subcortical brain nuclei that are anatomically situated between the cortex and thalamus. Hitherto, models of basal ganglia function have been based solely on the anatomical connectivity and changes in the rate of neurons mediated by inhibitory and excitatory neurotransmitter interactions and modulated by dopamine. Depletion of striatal dopamine as occurs in Parkinson's Disease (PD) however, leads primarily to changes in the rhythmicity of basal ganglia neurons. The general aim of this thesis is to use frontal electrocorticogram (ECoG) and basal ganglia local field potential (LFP) recordings in the rat to further investigate the putative role for oscillations and synchronisation in these structures in the healthy and dopamine depleted brain. In the awake animal, lesion of the SNc lead to a dramatic increase in the power and synchronisation of P-frequency band oscillations in the cortex and subthalamic nucleus (STN) compared to the sham lesioned animal. These results are highly similar to those in human patients and provide further evidence for a direct pathophysological role for p-frequency band oscillations in PD. In the healthy, anaesthetised animal, LFPs recorded in the STN, globus pallidus (GP) and substantia nigra pars reticulata (SNr) were all found to be coherent with the ECoG. A detailed analysis of the interdependence and direction of these activities during two different brain states, prominent slow wave activity (SWA) and global activation, lead to the hypothesis that there were state dependant changes in the dominance of the cortico-subthalamic and cortico-striatal pathways. Multiple LFP recordings in the striatum and GP provided further evidence for this hypothesis, as coherence between the ECoG and GP was found to be dependent on the striatum. Together these results suggest that oscillations and synchronisation may mediate information flow in cortico-basal ganglia networks in both health and disease.
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Oldenburg, Ian Anton. "Basal Ganglia Modulation of Cortical Firing Rates in a Behaving Animal." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13094354.
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Motor cortex, basal ganglia (BG), and thalamus are anatomically arranged in a recurrent loop whose activity is hypothesized to be involved in the selection of motor actions. Direct (dSPN) and indirect (iSPN) striatal projection neurons receive excitatory input from cortex, and are thought to oppositely modulate cortical activity via BG output to thalamus. Here, we test the central tenets of this model in head-restrained mice performing an operant conditioning task using optogenetic manipulation of dSPNs and iSPNs to determine the effects of activity in each pathway on primary motor cortex. We find that dSPN and iSPN activation has bidirectional, robust, and rapid effects on motor cortex that are highly context-dependent, with distinct effects of each pathway during quiescent and active periods. Thus, the effects of activity in each pathway are at times antagonistic and consistent with classic models, whereas in other behavioral contexts the two pathways will work in the same direction or have no effect at all. In a separate but related project, we describe a direct projection from the globus pallidus externa (GP), a central nucleus of the BG, to frontal regions of the cerebral cortex (FC), which is not typically included in models of BG function. Two cell types make up the GP-FC projection, distinguished by their electrophysiological properties, cortical projection patterns and expression of choline acyteltransferase (ChAT), a genetic marker for the neurotransmitter acetylcholine. These cholinergic GP cells receive basal ganglia input and bidirectionally modulate firing in FC of awake mice. Since GP-FC cells receive dopamine sensitive inhibition from iSPNs and dSPNs, this circuit reveals a pathway by which neuropsychiatric pharmaceuticals can act in the BG and yet modulate frontal cortices. Together, these two projects expand our understanding of the complexities of basal ganglia circuitry and its interactions with cortex.
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Marrow, Lynne. "Anatomical and behavioural investigations of the basal ganglia in the rat." Thesis, University of Reading, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333467.
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