To see the other types of publications on this topic, follow the link: GABAergic.
Dissertations / Theses on the topic 'GABAergic'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'GABAergic.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Gabor, Ronnie. "GABAergic mechanisms in adrenal enzyme regulation." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63939.
Full text
2
Benini, Ruba Sayed. "GABAergic signalling in temporal lobe epilepsy." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111818.
Full textAbstract:
Earlier studies on temporal lobe epilepsy (TLE), by focusing on the anatomical and electrophysiological abnormalities of the hippocampus, have attributed a major role to this limbic structure in the process of epileptogenesis and seizure generation. Recently however, there has been increasing evidence from both animal and human studies that other limbic structures, including the subiculum, the entorhinal cortex (EC, perirhinal cortex (PC) as well as the amygdala, are possibly involved in the process of epileptogenesis. With the help of both acute and chronic models of limbic seizures, I have used an electrophysiological approach to gain more insight into the mechanisms through which these structures could participate in the establishment of hyperexcitable neuronal networks. Particularly, my investigations have focused on assessing the role played by the subiculum, the amygdala and the PC in epileptiform synchronization in vitro. My findings demonstrate that seizure-induced cell damage in chronically epileptic mice results in a change in limbic network interactions whereby EC ictogenesis is sustained via a reverberant EC-subiculum pathway ( Chapter 1). Furthermore, I have discovered that the subiculum, which holds an anatomically strategic position within the hippocampus, is capable of gating hippocampul output activity via a GABAA-receptor mediated mechanism (Chapter 2). My investigations in the amygdala have confirmed that this limbic structure contributes to epileptiform synchronization (Chapter 3). Moreover, using a chronic rat model of TLE, I have found novel evidence suggesting that alterations in inhibitory mechanisms play a role in the increased excitability of the lateral amygdalar nucleus (Chapter 4). Finally, my studies in chronically epileptic rats have also led to preliminary data signifying hyperexcitability of the PC as well alterations in the interactions between the amygdala and this cortical structure (Chapter 5).
3
Cobb, Stuart Robert. "Synaptic interaction of hippocampal gabaergic neurones." Thesis, University of Oxford, 1996. http://ora.ox.ac.uk/objects/uuid:527682b7-2146-458a-b821-5dca9733e32f.
Full textAbstract:
Current concepts of hippocampal circuitry assume a large population of excitatory principal neurones whose activity is largely governed by a network of local-circuit GABAergic interneurones. The diversity of hippocampal local-circuit neurones and their synaptic control over principal cell activity was investigated in vitro, in order to define their synaptic connections and functional roles. Single and dual intracellular recordings were made from local-circuit neurones and pyramidal cells in area CA1 of the rat hippocampal slice. Interneurones were tentatively distinguished from pyramidal cells based on their firing as well as their membrane properties. Intracellular labelling of recorded cells with the marker biocytin revealed a diversity of cell types based on differential dendritic and axonal morphology and synaptic connections. The physiological data revealed that all types of interneurone tested evoked inhibitory postsynaptic potentials (IPSPs) in simultaneously recorded pyramidal cells. The IPSPs had fast rise and decay kinetics and the ones tested pharmacologically, were mediated by GABAA receptors. Similarly, individual interneurones were also shown to innervate other local-circuit interneurones in addition to pyramidal cells, the evoked effects being qualitatively similar in both types of postsynaptic targets. The postsynaptic effect and functional role of one type of hippocampal interneurone, the basket cell, was investigated in greater detail. Basket cell-evoked IPSPs were reliable, but showed some frequency-dependent attenuation. Moreover, basket cell IPSPs were found to interact with intrinsic pyramidal cell conductances to elicit rebound depolarisations and facilitate action potential generation. More detailed investigation showed that basket and axo-axonic cells were particularly effective in entraining pyramidal cell firing and sub-threshold membrane potential oscillations. Through these powerfully tuned mechanisms, sub-types of local-circuit interneurone provide a powerful mechanism to synchronise the activity of pyramidal cells. These results demonstrate a remarkable diversity of GABAergic local-circuit neurones in the hippocampal CA1 area and suggest that specific subtypes of cell mediate different functions.
4
Nasrallah, Fatma Faculty of Medicine UNSW. "A metabolic approach to the GABAergic system." Publisher:University of New South Wales, 2008. http://handle.unsw.edu.au/1959.4/43413.
Full textAbstract:
Here, we investigated the effects of modulation of the GABAergic system using a targeted neuropharmacological, 1H/13C NMR spectroscopy and metabolomic approach in Guinea pig cortical brain slices. The effects of exogenous GABA, agonists, antagonists and allosteric modulators at GABAA receptors were described and classified on the basis of metabolic activity; this corresponded to receptor location rather than pharmacology. The effects of agonists and antagonists at the GABAB receptor were described and classified into inhibitory and excitatory components, consistent with context dependent outcomes of receptor activity. Metabolic evidence for GABAC mediated activity in the cerebral cortex was identified for the first time indicating a strong role for this receptor in the control of neuronal activity. Inhibition of GABA uptake was examined using inhibitors of these transporters. The major effect of individual transporter subtype blockade was increased synaptic inhibition. The paradoxical activity of the GABA-transaminase inhibitor vigabatrin was resolved, with a direct demonstration of a single inhibitory mechanism mediated via this drug, via a mechanism also induced by antagonists at the GABAC receptor. These data were then integrated using multivariate statistics to identify 5 subclasses of activity which corresponded to receptor location (e.g. synaptic or extrasynaptic) rather than receptor pharmacology. This represents a novel and powerful new approach to the study of brain metabolism and the GABAergic system.
5
Nicholson, Martin William. "Diazepam-dependent modulation of GABAergic inhibitory synapses." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046265/.
Full textAbstract:
Diazepam is an allosteric modulator of GABAA receptors which potentiates GABAA receptor activity resulting in enhanced inhibitory synaptic transmission. Diazepam is used to treat anxiety, insomnia and seizures, however, its use is limited due to the development of tolerance. Here I show that prolonged treatment of cortical neurones with diazepam triggers endocytosis and subsequent downregulation of cell-surface GABAA receptors. Using pharmacological reagents, I have demonstrated that diazepam triggers PLC-dependent release of calcium from the endoplasmic reticulum which activates the phosphatase calcineurin resulting in dephosphorylation of the γ2 subunit of GABAA receptors and their endocytosis. This was elucidated using a combination of biochemical and cell biological approaches. In addition, I have developed HEK293 cell lines stably expressing various subtypes of GABAA receptors to investigate further diazepam and isoguvacine-dependent regulation of GABAA receptors. The same calcium-dependent signalling pathway that regulates cell-surface stability of GABAA receptors in neurones was found to operate in HEK293 cells. Subsequently, I focused on a key component of this signalling pathway; PLCδ1. Using biochemical techniques I have demonstrated that PLCδ1 binds directly to the GABAA receptor β3 subunit at two independent sites. This binding was confirmed by coimmunoprecipitation of PLCδ1 and GABAA receptors from cortical neuronal lysates. Interestingly, upon diazepam treatments, PLCδ1 was shown to dissociate from GABAA receptors, thus leading to mobilisation of calcium from the intracellular stores and activation of calcineurin. To assess how changes in cell-surface expression of GABAA receptors affect the stability of GABAergic synapses, I characterised the size and number of post-synaptic GABAA receptor clusters and the number of presynaptic GABA-releasing terminals following chronic diazepam treatment. I observed a reduction in the size and number of post-synaptic GABAA receptor clusters and a reduction in the number of GABA-releasing terminals. These data are consistent with the loss of cell-surface GABAA receptors following long-term treatments of cortical neurones with diazepam. These changes correlated with an increase in the expression of the early apoptosis marker, cleaved-caspase 3, in glutamatergic neurones suggesting indirect cytotoxic effects of diazepam treatments. The loss of inhibitory GABAergic synapses following chronic diazepam treatment may contribute to the well-known development of tolerance to these clinically important therapies for stress- and anxiety- related neurological disorders.
6
Ma, Wenqian. "Dlx Gene Regulation of Zebrafish GABAergic Interneuron Development." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/19970.
Full textAbstract:
Abstract
The Dlx genes play an important role in the differentiation and migration of
gamma-aminobutyric acid (GABA) interneurons of mice. GABAergic interneurons
are born in the proliferative zones of the ventral telencephalon and migrate to the
cortex early during mouse development. Single Dlx mutant mice show only subtle
phenotypes. However, the migration of immature interneurons is blocked in the
ventral telencephalon of Dlx1/Dlx2 double mutant mice leading to reduction of
GABAergic interneurons in the cortex. Also, Dlx5/Dlx6 expression is almost entirely
absent in the forebrain, most probably due to cross-regulatory mechanisms.
In zebrafish, the role of dlx genes in GABAergic interneuron development is
unknown. By injecting Morpholino, we double knocked down dlx1 and dlx2 genes in
wildtype zebrafish to investigate the function of the two genes in zebrafish
GABAergic interneuron development. By comparing different subsets of GABAergic
interneuron development in wildtype and dlx1/2 morphant zebrafish forebrain, we
found out that at 3dpf, 4dpf and 7dpf, double knockdown of dlx1 and dlx2 genes in
zebrafish remarkably reduced the number of Calbindin-, Somatostatin- and
Parvalbumin-positive GABAergic neurons, whereas the development of
Calretinin-positive neurons is slightly affected. These results suggest that in zebrafish,
dlx1a and dlx2a genes are important for the development of certain subtypes of
GABAergic interneurons (Calbindin-, Somatostatin- and Parvalbumin-positive
neurons) and may have minor influence on Calretinin-positive neuron development.
This also suggests that different regulatory mechanisms are involved in the
development of the different subtypes of GABAergic interneurons.
7
Garden, Derek Leonard Frank. "GABAergic transmission in the perirhinal cortex in vitro." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274770.
Full text
8
Huff, Courtney L. M. S. "MDMA and Glutamate: Implications for Hippocampal GABAergic Neurotoxicity." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460444662.
Full text
9
Mabey, Jennifer Kei. "Synaptic Plasticity in GABAergic Inhibition of VTA Neurons." BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/5256.
Full textAbstract:
Past research has demonstrated that the motivational effects of opiates causes a change in ventral tegmental area (VTA) γ-amino butyric acid (GABA) subtype A receptor [GABA(A)R] complexes in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of VTA GABA neurons to a GABA-induced depolarization. Previously shown in naïve animals, superfusion of ethanol (IC50 = 30 mM) and the GABA(A)R agonist muscimol (IC50 = 100 nM) decreased VTA GABA neuron firing rate in a dose-dependent manner. The aim of this study was to evaluate VTA GABA neuron excitability, GABA synaptic transmission to VTA GABA neurons, and a potential switch in GABA(A)R functionality produced by alcohol dependence. To accomplish these studies, we used standard whole-cell, perforated patch, and attached-cell mode electrophysiological techniques to evaluate chronic ethanol effects on VTA GABA neurons in CD-1 GAD GFP mice, which enable the visual identification of GABA neurons in the slice preparation. In order to more conclusively demonstrate synaptic plasticity in VTA neurons associated with alcohol dependence, three studies were proposed to elucidate the mechanism underlying the switch in GABA synaptic function with dependence. First, we evaluated the effects of withdrawal from chronic ethanol exposure on muscimol-induced inhibition of VTA GABA neuron firing rate. Second, we evaluated the effects of withdrawal from chronic ethanol exposure on GABA(A)R-mediated synaptic responses in VTA GABA neurons by looking at eIPSCs, and corresponding changes in VTA DA neuron firing rate. Third, we evaluated chloride reversal potentials in VTA GABA neurons using perforated patch recordings in VTA GABA neurons.Through these studies, we found that there was less sensitivity to muscimol in animals treated with ethanol versus air-exposed controls. However, it is yet to be shown more conclusively if VTA GABA neurons undergo a switch in GABA(A)R function with chronic ethanol.
10
COLACI, FRANCESCO. "GABAergic synaptic protein dynamics measured by spectroscopic approaches." Doctoral thesis, Università degli studi di Genova, 2018. http://hdl.handle.net/11567/929825.
Full textAbstract:
The activity dependent adjustment of synaptic strength (synaptic plasticity) involves the reorganization of post-synaptic proteins. The fast diffusion of synaptic proteins has been shown to play an important role in such molecular rearrangements. Taking advantage of single particle tracking (SPT) and fluorescence recovery after photobleaching (FRAP) techniques, it has been demonstrated that during inhibitory long-term potentiation (iLTP) the scaffold protein gephyrin and GABAA receptors are accumulated and immobilized at post-synaptic inhibitory sites.
11
Mellor, Jack Robert. "Electrophysiological investigation of the mechanisms underlying GABAergic synaptic transmission." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624122.
Full text
12
Bienvenu, Thomas Claude Michel. "Functional specialisation of GABAergic cells in the basolateral amygdala." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:d52fb5ad-19cc-41b8-a1e2-2f25ef82dddf.
Full textAbstract:
The amygdala, in particular its basolateral part (BLA), plays a critical role in binding affective qualities to otherwise neutral stimuli, and in eliciting emotional behaviors. Plasticity of inputs to BLA projection neurons involved in emotional memory has been extensively studied. However, how BLA neurons collectively process sensory information to encode and stabilize emotional memories is unknown. Precise coordination of BLA network activities seems critical. Specifically, timed integration of salient stimuli, and synchrony with hippocampal theta oscillations appear to be important. Recent reports suggest that GABAergic neurons may be instrumental in shaping ensemble activity in the BLA. Studies of neocortex and hippocampus showed that diverse GABAergic interneuron types play highly specific roles in coordinating network operations. The presence of similar interneuron populations in the BLA suggests comparable mechanism may govern its activities. However, GABAergic cell types and their functions have not been characterized.
13
Pallotto, Marta. "GABAergic signaling and synaptic integration of adult-generated neurons." Paris 6, 2012. http://www.theses.fr/2012PA066677.
Full textAbstract:
La neurogenèse adulte représente une forme unique de plasticité neuronale, qui, chez les mammifères, est limitée à l’hippocampe et au système olfactif. Dans le bulbe olfactif (BO) les neurones s’intègrent sans cesse aux réseaux préexistants et se différentient. La majorité de ces cellules forment une population d’interneurones GABAergique : Les cellules granulaires (GCs). Dans ce travail, j’ai étudié l’intégration synaptique des GCs nouvellement générées dans le BO de souris adultes. Afin de visualiser ces cellules, j’ai injecté un vecteur viral codant pour l’eGFP dans le courant de migration menant les cellules vers le BO. J’ai ainsi pu suivre leur développement en les observant à différents jours post-injection (jpi). J’ai pu constater que les jeunes GCs commencent à recevoir des contacts synaptiques dés qu’elles atteignent leur destination finale dans le BO. En effet les premiers contacts synaptiques sur des cellules GFP+ sont détectés dans la couche des cellules granulaires à 3 jpi. J’ai aussi constaté que, durant une première phase, les synapses GABAergiques sont plus nombreuses que les synapses glutamatergique. Ceci m’a conduit à émettre l’hypothèse suivante : Puisque la transmission GABAergique est prédominante dans les premières phases du développement des GCs nouveau-nées, elle pourrait jouer un rôle important dans leur intégration synaptique, leur maturation et leur survie. Afin de vérifier cette hypothèse, j’ai utilisé la délétion conditionnelle (CRE-LoxP) du gène Gabra2 codant pour la sous-unité α2 du récepteur GABA (GABAAR) qui est la principale sous-unité exprimée par les GCs. Utilisant deux modèles de souris transgéniques permettant la délétion spécifique dans une population de cellules produites chez l’adulte, j'ai vérifié que l'ablation de la sous-unité α2 est accompagnée par une réduction dramatique de fréquence et d’amplitude des courants synaptiques GABAergiques reçues par les GCs. Cette activité GABAergique réduite n’affecte pas la survie des GCs, mais retarde dramatiquement leur maturation. Dans les cellules mutantes, la complexité de l’arborisation dendritique et la densité des épines sont réduites. Ces altérations sont accompagnées par un déplacement des synapses excitatrices, des épines vers les troncs dendritiques. De plus, la délétion de la sous-unité α2 réduit la plasticité structurale des cellules normalement induite par la manipulation de l’environnement sensoriel olfactif et donc de l’activité perçue par les cellules. Ces résultats montrent qu'une signalisation GABAergique adéquate est requise pour le développement morphologique et l'intégration synaptique des GCs produites chez l’adulte, et révèle un rôle inattendu des synapses GABAergiques dans la formation de l’arborisation dendritique et dans la synaptogenèse glutamatergiqueAdult neurogenesis represents a unique form of brain plasticity. In mammals the genesis of new neurons is mainly restricted to the dentate gyrus of the hippocampus and the olfactory bulbs. In the olfactory bulb (OB), neurons are continuously added to pre-existing networks and differentiate mainly into GABAergic local interneurons: granule cells (GCs) and periglomerular cells (PGCs). These interneurons mature and integrate in the OB network acquiring an adult phenotype. In the present work, I investigated the synaptic integration of adult-generated GCs in the mouse OB. I took advantage of local injections of eGFP encoding lentiviral vector to visualize through GFP fluorscent labelling new-born GCs in the adult OB at different times after their genesis. I found that adult-generated GCs start to receive synaptic contacts as soon as they reach their final destination in the OB. In fact, the first synaptic inputs onto GFP-positive cells were detected in the granule cell layer at 3 days post-injection (dpi). Interestingly, I found that at early stages GABAergic synapses were more abundant than glutamatergic contacts, suggesting that GABA may play an important role in the synaptic integration, maturation and survival of newborn GCs. To verify this hypothesis, I used Cre-mediated conditional deletion of the Gabra2 gene encoding for the 2 subunit of the GABAA receptor (GABAAR) to functionally disrupt afferent GABAergic transmission in migrating GC precursors. Using two different transgenic mouse models, I found that ablation of the 2-subunit was accompanied by a dramatic reduction in the frequency and amplitude of spontaneous or evoked GABAergic IPSCs. Remarkably, this reduced GABAergic activity did not affect GC survival but delayed dramatically their maturation. In mutant cells, dendritic branching and spine density were reduced, and spine loss was accompanied by a mislocation of excitatory synapses from spine heads to dendritic shafts. Moreover, deletion of the 2 subunit occluded structural plasticity of spines inducible by odor-enrichment and odor-deprivation protocols. These results show that proper GABAergic signaling is required for the morphological development and synaptic integration of adult-born GCs, and reveal an unexpected function of early GABAergic inputs in controlling spine formation and glutamatergic synaptogenesis
14
Mazo, Camille. "GABAergic signaling in cortical feedback to the olfactory bulb." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066066/document.
Full textAbstract:
Les projections corticales de retour conduisent l'information vers des relais de traitement de l'information plus précoces. Elles sont essentielles pour la perception sensorielle. En ce qui concerne l'olfaction, l'information sensorielle est constituée d'une multitude de molécules odorantes, et c'est ce mélange complexe qui pénètre dans la cavité nasale. En fonction du contexte, c'est une partie ou une autre de cet ensemble de molécules qui va être importante d'un point de vue comportemental. Les signaux corticaux de retour permettraient de focaliser son attention sur les odeurs pertinentes de l'environnement. Au cours de mon doctorat, j'ai étudié le rôle de la signalisation inhibitrice GABAergique dans ces retours corticaux vers le bulbe olfactif, le premier relais de l'information olfactive. La première partie de mon travail a mis en évidence une modulation métabotropique GABAergique du retour cortical excitateur. Nos expériences caractérisent ensuite l'effet produit par cette modulation sur le bulbe olfactif. Nous avons ainsi démontré que la signalisation GABAergique au niveau de retours corticaux change de manière profonde la réponse du bulbe olfactif aux stimuli olfactifs. Dans un deuxième temps, j'ai trouvé que le cortex olfactif envoie non seulement des projections de retour excitatrices, mais aussi des retours inhibiteurs. Des expériences précisent ensuite la localisation de ce retour GABAergique, ainsi que son impact sur le bulbe olfactif. Nous avons notamment observé qu'en manipulant l'activité de ces fibres GABAergiques, nous pouvions modifier le comportement olfactifCortical feedback conducts information towards earlier relays of information processing. It is instrumental for sensory perception. In the olfactory system, odorants are never experienced in isolation by the nose, and they might be meaningful to the animal or not depending on the context. Feedback inputs onto early processing stages are poised to permit selective attention to the relevant odorants in the olfactory scene. During my thesis work, I focused on understanding the key role that inhibitory GABAergic signaling plays in the cortical feedback to the olfactory bulb in mice.The first part of my work started with the discovery of excitatory transmission between cortical feedback inputs and the olfactory bulb is modulated by metabotropic receptors for GABA. Next, the impact of this regulation on the olfactory bulb network was investigated. We found that GABAergic signaling at cortical feedback axons profoundly changes the response of the olfactory bulb output cells to odor stimulation. In the second part of my thesis, I found that the cortical projections to the olfactory bulb not only comprises of excitatory components, but also inhibitory components. The precise origin of this GABAergic feedback was then determined and its impact on the olfactory bulb network is currently assessed. In particular, we observed that manipulating the activity of this GABAergic feedback perturbs olfactory behavior
15
Verkuyl, Jan Maarten. "Stress, corticosterone and GABAergic inhibition in the rat paraventricular nucleus." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/70710.
Full text
16
Ferrigan, Leanne M. "Synaptic interactions between cholinergic and GABAergic systems of the hippocampus." Thesis, University of Glasgow, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410010.
Full text
17
Baker, Christian. "Developmental challenge and GABAergic neuronal abnormalities : their relevance to schizophrenia." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.274951.
Full text
18
Tanaka, Yasuyo. "Local connections of layer 5 GABAergic interneurons to corticospinal neurons." Kyoto University, 2012. http://hdl.handle.net/2433/152493.
Full text
19
Uusisaari, Marylka. "GABAergic mechanisms of excitation and hypersynchrony in adult rat hippocampus." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/uusisaari/.
Full text
20
Fan, Kai Yoon. "GABAergic synaptic transmission, plasticity and integration in the subthalamic nucleus." Thesis, University of Sheffield, 2012. http://etheses.whiterose.ac.uk/3167/.
Full text
21
Carus-Cadavieco, Marta. "Coordination of innate behaviors by GABAergic cells in lateral hypothalamus." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19135.
Full textAbstract:
Der laterale Hypothalamus (LH) reguliert angeborene Verhaltensweisen. Ob und wie die Koordination von hypothalamischen Neuronengruppen Verhaltensübergänge reguliert, blieb jedoch unbekannt. In dieser Arbeit wurde Optogenetik mit neuronalen Ableitungen in verhaltenden Mäusen kombiniert. LHVgat Neurone erhöhten ihre Aktivitätsrate während Übergängen vom NREM-Schlaf zum Wachzustand. LHVgat Zellen projizieren zum Nucleus reticularis des Thalamus (RTN). Optogenetische Aktivierung von Vgat Ausgängen im RTN führte eine starke, frequenzabhängige Inhibierung von RTN Zellen herbei und replizierte Verhaltenszustands-abhängige Aktivitätsraten in RTN Neuronen. Ableitungen von LH Neuronen während Umgebungserkundung ergaben, dass 65% der LH Neurone ihre Aktivitätsrate erhöhten, wenn das Tier began sich fortzubewegen. 'Top-down’ Vorderhirn Innervation des LH erfolgt größtenteils durch Signale ausgehend vom lateralen Septums (LS). Während spontaner Umgebungserkundung und freiem Zugang zu Futter wiesen der LH und das LS Gamma-Oszillationen (30-90 Hz) auf, welche neuronale Aktivität innerhalb und zwischen diesen beiden Gehirnregionen synchronisierten. Optogenetische Stimulation von Somatostatin-positiven GABAergen Projektionen zum LH mit Gamma-Frequenz förderte die Nahrungssuche und erhöhte die Wahrscheinlichkeit des Betretens der Nahrungszone. Inhibitorische Signale des LS bewirkten eine Unterteilung der LH Neurone: entsprechend ihrer Aktivität im Bezug zur Nahrungsstelle wurden sie während bestimmter Phasen der Gamma-Oszillation aktiviert. Dabei führte optogenetische Stimulation von LS-LH Neuronen mit Gamma-Frequenz keine Veränderung bei der Nahrungsaufnahme selbst herbei. Insgesamt liefert diese Arbeit neue Einsichten über die Funktion der neuronalen Netzwerke des LH, welche durch Signalgebung mit unterschiedlichen Zeitskalen über die Koordination mit vor- und nachgeschalteten neuronalen Netzwerken Übergange zwischen verschiedenen angeborenen Verhaltensweisen regeln.Lateral hypothalamus (LH) is crucial for regulation of innate behaviors. However, it remained unknown whether and how temporal coordination of hypothalamic neuronal populations regulates behavioral transitions. This work combined optogenetics with neuronal recordings in behaving mice. LHVgat cells were optogenetically identified. LHVgat neurons increased firing rates upon transitions from non-REM (NREM) sleep to wakefulness, and their optogenetic stimulation during NREM sleep induced a fast transition to wakefulness. LHVgat cells project to the reticular thalamic nucleus (RTN). Optogenetic activation of LHVgat terminals in the RTN exerted a strong frequency-dependent inhibition of RTN cells and replicated state-dependent changes in RTN neurons activity. Recordings of LH neurons during exploration revealed that 65% of LH neurons increased their activity upon the onset of locomotion. Top-down forebrain innervation of LH is provided, to a great extent, by inhibitory inputs from the lateral septum (LS). During spontaneous exploration in a free-feeding model, LS and LH displayed prominent gamma oscillations (30-90 Hz) which entrained neuronal activity within and across the two regions. Optogenetic gamma-frequency stimulation of somatostatin-positive GABAergic projections to LH facilitated food-seeking, and increased the probability of entering the food zone. LS inhibitory input enabled separate signaling by LH neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. In contrast to increased food intake during optogenetic stimulation of LHVgat cells, food intake during gamma-rhythmic LS-LH stimulation was not changed. Overall this works provides new insight into the function of LH circuitry, that employs signalling at different time scales, which, in coordination with upstream and downstream circuits, regulates transitions between innate behaviors.
22
Doll, Daniel. "GABAergic inhibition regulates the synaptic activation of cholinergic-dependent plateau potentials." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ31343.pdf.
Full text
23
Singh, Bhumika. "Differential regulation of glutamatergic and GABAergic synaptogenesis by BDNF and PRG1." [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/339/index.html.
Full text
24
Berghuis, Paul. "Brain-derived neurotrophic factor and endocannabinoid functions i GABAergic interneuron development /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-125-8/.
Full text
25
Asseri, Khalid. "Effects of AMBD and isovaline on GABAergic transmission in thalamic neurons." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/35078.
Full textAbstract:
In central neurons, the endogenous amino acid γ-aminobutyric acid (GABA) exerts synaptic inhibition mediated through ionotropic GABAA-, or metabotropic GABAB-receptors. These receptors exist on both pre- and postsynaptic membranes. The synthetic structural analogues of GABA, 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide (AMBD) and R-isovaline have received little study on synaptic inhibition in the mammalian thalamus. AMBD was originally proposed as a taurine antagonist whereas R-isovaline is a non-biogenic amino acid that increases postsynaptic K⁺ conductance of thalamocortical neurons. The aim of this work was to assess the prediction that AMBD and R-isovaline would affect presynaptic release of GABA onto neurons of ventrobasal nuclei.
AMBD and R-isovaline were applied by perfusion of thalamic slices obtained from juvenile Sprague-Dawley rats (P10 -13). During whole-cell patch clamp recording from thalamocortical neurons, we voltage-clamped neurons at a holding potential of -70 mV. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded in the presence of tetrodotoxin (TTX). Kynurenic acid and internal Cs⁺ were used to block postsynaptic glutamate receptors and K⁺ conductances. We used the GABAA antagonist bicuculline to identify GABAergic mIPSCs, without affecting a possible presynaptic GABAB-component.
Applied alone at 250 μM, AMBD had no effect on the passive and active membrane properties of neurons. In the range of 10 µM to 1 mM, AMBD had no effect on amplitude or decay time constant of GABAergic mIPSCs. Acting with an IC₅₀ of 232 μM, AMBD reversibly reduced the frequency of GABAergic mIPSCs. The above observations implied that AMBD reduced presynaptic release of GABA. In a range of 25 to 200 µM, R-isovaline had no effect on the holding current or frequency, amplitude and decay time constant of GABAergic mIPSCs. Hence, R-isovaline did not affect release of GABA and did not affect receptors on nerve terminals.
In summary, AMBD reversibly decreased the presynaptic release of GABA, likely by an action on nerve terminals while having no effects on postsynaptic membrane properties that could account for the reduced frequency of GABAergic mIPSCs. The exact mechanism whereby AMBD decreased GABA release remains unclear. R-isovaline had no effect on GABA release in ventrobasal nuclei.
26
Sambandan, Sivakumar. "Associative synaptic plasticity in GABAergic interneurons of the rat dentate gyrus." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158478.
Full textAbstract:
The dentate gyrus (DG) is a sub-region of the hippocampus which is important for memory formation and storage in the brain. It comprises two major classes of neurons called granule cells (GCs), the local principal cells and the interneurons which receive sensory information from the entorhinal cortex (EC). The GCs contain glutamate as neurotransmitter and excite the postsynaptic cells whereas the interneurons release GABA and inhibit the target cells. While the GCs are abundant in number and transmit the processed information to CA3 via mossy fibres (MFs), the interneurons determine when and where the information flows through the principal cell network. To understand how information is processed in DG, it is paramount to understand the role of interneurons in the network in detail. Moreover, disruption of this basal transmission set-up forms the basis of many neurological disorders. For example, reduced inhibition on GCs is implicated in epilepsy. Treatment/prevention of such diseases also necessitates better understanding of the role of inhibition in DG. While greater degree of knowledge exists on how interneurons inhibit GCs, how they are activated by afferent inputs is not clear. Hence, the present work is primarily focussed on studying the physiology behind synaptic activation of interneurons by afferent excitatory inputs in DG. The results obtained might help in studying the causes of pathological conditions of DG in addition to elucidating the circuit mechanisms of information processing.
27
Richards, Blake Aaron. "The role of GABAergic circuits in stimulus-instructed receptive field development." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533845.
Full text
28
Cao, Zhiwen, and 曹志文. "GABAergic transmission in developmental establishment of a gravity-related spatial reference." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47151304.
Full textAbstract:
In rats, the subnuclei of the inferior olive (IO) and thalamus exist
topographic spatial representation to sinusoidal horizontal linear translations along either the antero-posterior or interaural direction. To examine the effect of GABAergic neurotransmission within the vestibular nucleus on the establishment of gravity-related topographic spatial representation in relay station of the central vestibular pathway, GABAA receptor antagonist bicuculline was used to chronically perturb GABA transmission within the vestibular nucleus of postnatal rats. Implantation of bicuculline-loaded or saline-loaded Elvax slice onto the dorsal surface of vestibular nucleus was performed in P1 rats which were allowed to recover into adulthood. Fos protein expression was used as an indicator to identify central neurons responsive to horizontal linear accelerations. In stationary or labyrinthectomized rats, Fos-immunoreactive (ir) neurons were either absent or sporadically scattered throughout the IO and thalamic subnuclei, indicating that the Fos expression in these neural area was otolithic in origin. In the saline control group, Fos expression induced by horizontal antero-posterior linear acceleration was observed in both the IO and thalamus. Responsive IO subnuclei include β subnucleus of IO and dorsomedial cell column while those in the thalamus include central medial nucleus, paracentral nucleus, mediodorsal nucleus, central lateral nucleus, zona incerta and subparafascicular nucleus of thalamus. For-ir neurons responsive to horizontal interaural linear acceleration were found in those IO subnuclei and thalamic subnuclei. When compared with the saline-treated group, the number of Fos-ir IO neurons responsive to horizontal linear acceleration was significantly lower in adult rats perturbed with bicuculline at P1. Besides, the pattern of Fos expression in both the IO and thalamus was altered in adult rats pretreated with bicuculline. In the utricle-related thalamic subnuclei, the postnatal time when Fos-ir neurons were found triggered by otolithic stimulation was delayed and the number of these Fos-ir neurons was fewer in the bicuculline-treated group than those in the saline-treated group. To investigate whether there exists a critical period for postnatal establishment of topographic spatial representation in the IO and thalamus, implantation of bicuculline-loaded Elvax slice onto the vestibular nucleus was carried out in P14 rats. The topographic spatial representation in IO and thalamus of those rats were unchanged as compared with adult rats pretreated with saline at P14. These results indicate that the GABAergic neuronal circuit in the vestibular nucleus plays an important role in postnatal establishment of topographic spatial representation in the central vestibular system. Most importantly, we documented the occurrence of a postnatal critical period (between P1 and P14) during which GABAergic transmission
regulated the formation of a gravity-related spatial framework in the brain.published_or_final_version
Physiology
Master
Master of Philosophy
29
Joshi, Abhilasha. "Behaviour-dependent activity and synaptic organisation of septo-hippocampal GABAergic neurons." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:28b4b2bc-f782-4bc9-87af-233527171e60.
Full textAbstract:
Animal behaviour is coordinated by biological rhythms over multiple timescales. In the temporal cortex, rhythmic oscillatory activity in the 5 to 12 Hz theta frequency range supports behaviour through temporal windows of changes in excitability and circuit computation. Subcortical inputs, including those from the medial septum are thought to generate the theta oscillatory activity. However, the rules of innervation of identified types of cortical cells in different cortical regions by a diverse population of septal neurons are largely unknown. During my DPhil studies, I tested the hypothesis that medial septal GABAergic neurons which exhibit distinct activity patterns would express distinct molecular marker combinations and have distinct synaptic partners. In Chapters 1 and 2, I formulate my research questions and explain the methodology used. My main findings are presented in chapters 3 to 7. In Chapter 3, I present the strategy used to identify four populations of rhythmic medial septal neurons based on their spike-train dynamics in the mouse in vivo. In Chapter 4, I present a detailed analysis of the spike-timing and molecular parameters of a specialised population of rhythmic neuron, the Teevra cells. Teevra cells are PV+, do not change their firing rate from rest to running and fire short bursts of action potentials preferentially at the trough of both CA1 theta and slow irregular activity recorded in stratum pyramidale. In Chapter 5, I show that Teevra cells selectively innervate axo-axonic cells and CCK-immunopositive interneurons in hippocampal area CA3, bypassing CA1, CA2, and the dentate gyrus. In Chapter 6, I show that Teevra cell axons terminate in restricted septo-temporal segments of CA3 according to their rhythmicity. Finally, in Chapter 7, I present the Komal cells, which fire long bursts of action potentials at the peak of theta, increase their firing rate during running, and preferentially innervate extrahippocampal cortices. I discuss the broad relevance of my observations in Chapter 8. Overall, my results show an unexpected specialisation in the organisation of medial septal GABAergic inputs to the temporal cortex. Teevra cells fire maximally at the trough and preferentially innervate the CA3 whereas Komal cells fire maximally at the peak and target extrahippocampal cortices, thereby coordinating the timing of converging glutamatergic inputs to CA1 via disinhibition. This cortical-region-specific GABAergic innervation by physiologically distinct septal neuronal types suggests a general mechanism for the coordination of network activity, both during regular theta oscillations and irregular large amplitude waves, providing windows of computation through synchronisation of neuronal activity in the cortex.
30
Hunt-Jones, Charlotte Amy. "Mutation analysis of GABAergic neuroinhibitory genes in childhood genetic generalised epilepsies." Thesis, Swansea University, 2015. https://cronfa.swan.ac.uk/Record/cronfa43036.
Full textAbstract:
Epilepsy affects over 450,000 people in the UK and there are over 50 epilepsy phenotypes; genetic generalised epilepsy (GGE) account for up to 30% of seizure types. It is established that GGE and other neurological disorders are, in some cases, caused by channelopathies within post-synaptic inhibitory neurotransmitter systems such as GAB A (epilepsy) and Glycine (hyperekplexia). GAB A is the primary inhibitory neurotransmitter in the brain and is synthesised from glutamate by GAD65 and 67, and is released from the pre-synaptic nerve terminal into the synaptic cleft, where it binds to post-synaptic GABA receptors and initiate neuroinhibition. This inhibition is removed by post-synaptic GABA transporters (GAT1 and GAT3) that uptake GABA back into the cell for re-packaging in presynaptic vesicles or breakdown by transamination. Abnormalities in this system have been linked to diseases including anxiety, psychosis, Parkinsons’s Disease and epilepsy. GABAergic animal models have demonstrated a tendency to seizure, including GABA transporter and enzyme models in relation to epilepsy. Given the above, the aim of this study was to identify GGE causing variants in four GABAergic genes. GGE patient samples (n=101) were recruited from 3 global centres and screened for variations in GAT1, GAT3, GAD65, GAD67 using high-throughput LightScanner analysis and bi-directional Sanger sequencing. Control population studies («=480) were carried out and analysis of online databases to determine the frequency of variants. Twenty novel or very rare variants were identified in 48 patient samples representing a detection rate of 6.8%, where a clustering of phenotypes included a predisposition towards absence seizures. The biological consequences of these variants were predicted using three online predictive programmes, multiple phylogenetic alignments and 3D structural modelling. Mutation expression constructs were prepared and expression levels were validated by immunocytochemistry. Functional characterisation of these variants will hopefully improve genetic diagnosis in GGE and determine causality of GABAergic absence seizures.
31
Paraskevopoulou, Foteini [Verfasser]. "Investigation of striatal GABAergic output modulation by glutamatergic input / Foteini Paraskevopoulou." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1234984288/34.
Full text
32
Wołoszynowska-Fraser, Marta Urszula. "Function of prefrontal GABAergic interneurons in behaviour : a relevance to schizophrenia." Thesis, University of Aberdeen, 2016. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=229738.
Full textAbstract:
The inhibitory circuitry of the prefrontal cortex (PFC) is involved in working memory and modulation of brain oscillations. Alterations in this network and especially GABAergic cells that express cholecystokinin (CCK), parvalbumin (PV), or somatostatin (SST) may underlie some of the cognitive deficits observed in schizophrenia. To assess the involvement of CCK+, PV+, and SST+ interneurons in PFC-dependent behaviours, we selectively inactivated these in prelimbic and infralimbic PFC via virus-mediated expression of tetanus toxin light chain (TeLC). We found that functional removal of CCK+ or PV+, but not SST+ neurons leads to specific impairments in working memory, and these represent the main cognitive domains affected in schizophrenia. PV-TeLC and CCK-TeLC mice displayed significant Y-maze alternation index reduction (p < 0.05). Targeting of PV+ prefrontal cells causes anxiety-like phenotype. Moreover, PV+ and SST+, but not CCK+ interneurons, appear to play a role in latent inhibition. Functional removal of CCK+, PV+ and CCK+ cells from PFC does not affect circadian activity and does not cause anhedonia. The involvement of PV-network in generation of neuronal activity and acetylcholine homeostasis was assessed. For neurophysiological recordings, each arm of the Y-maze divided into two equal-sized zones – proximal (close to the central decision point) and distal (far end). Zone entry was event-mapped onto continues local field potential recordings from medial PFC and CA1 region of the hippocampus. PV-TeLC animals displayed significantly lower prefrontal power in the decision zone. This suggests that the PV-TeLC animals are unable to modulate neuronal activity depending on the cognitive demand. Functional removal of prefrontal PV+ interneurons also leads to disturbed acetylcholine homeostasis. These results show that prefrontal GABAergic cells drive different behaviours and control task-relevant neuronal activity in different brain regions engaged with working memory such as hippocampus. Similar signalling anomalies may thus underlie cognitive deficits found in schizophrenia.
33
Nakamura, Shoko. "Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum." Kyoto University, 2005. http://hdl.handle.net/2433/144485.
Full text
34
Tomioka, Ryohei. "Demonstration of long-range GABAergic connections distributed throughout the mouse neocortex." Kyoto University, 2005. http://hdl.handle.net/2433/144762.
Full textAbstract:
Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第11438号
医博第2861号
新制||医||895(附属図書館)
23081
UT51-2005-D188
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 河野 憲二, 教授 大森 治紀, 教授 髙橋 良輔
学位規則第4条第1項該当
35
Parker, Krystal 'Detweiler'. "The role of cerebellar nuclear GABAergic neurotransmission in eyeblink motor control." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3355523.
Full text
36
Asiedu, Marina N. "Spinal Sensitization Mechanisms Promoting Pain: Gabaergic Disinhibition and Pkmζ-Mediated Plasticity." Diss., The University of Arizona, 2012. http://hdl.handle.net/10150/232496.
Full textAbstract:
As a major public health problem affecting more that 76.5 million Americans, chronic pain is one main reason why people seek medical attention. It is a pathological nervous system disorder that persists for months or years. Sensitization of nociceptive neurons in the dorsal horn of the spinal cord is crucial in the development of allodynia and hyperalgesia. The work presented in this thesis will focus on spinal protein kinase M zeta (PKMζ)-mediated plasticity and GABAergic disinhibition as spinal amplification mechanisms that orchestrate persistent changes in the dorsal horn of the spinal cord. As a result of central sensitization following peripheral nerve injruy, GABAergic disinhibition occurs due to an alteration in Cl- homeostasis via reduced KCC2 expression and function. Intrathecal administration of acetazolamide (ACT), a carbonic anhydrase inhibitor, attenuated neuropathic allodynia and spinal co-adminitation of ACT and midazolam (MZL), an allosteric modulator of the benzodiazepine class of GABAA receptors, synergistically inhibited neuropathic allodynia. Further studies concerning the impact of altered Cl-homeostasis via reduced KCC2-mediated Cl-extrusion capacity on the analgesic efficacy and potency of GABAA receptor agonist and allosteric modulators revealed that there is a differential regulation of the agonists and allosteric modulators at the GABAA receptor complex when Cl-homeostasis is altered. Another spinal amplification mechanism leading to central sensitization is PKMζ-mediated spinal LTP. In model of persistent nociceptive sensitization, allodynia induced by IL-6 injection or plantar incision was abolished by both the inhibition of protein translation machinery and PKMζ inhibitor, ZIP. However, only PKMζ inhibition prevented the enhanced pain hypersensitivity precipitated by a subsequent stimulus after the initial hypersensitivity had resolved, asserting that spinal PKMζ underlies the maintenance mechanisms of persistent nociceptive sensitization. Also, these results confirmed that the initiation mechanisms of persistent sensitization parallel LTP initiation mechanisms and the maintenance mechanisms of persistent sensitization parallel LTP maintenance mechanisms. Taken together, these results indicate that these amplification mechanisms drive a chronic persistent state in these models such that inhibition of these spinal amplication mechanisms will serve as an effective approach in the quenching chronic pain hypersensitivity in chronic pain models.
37
Kasap, Zeynep. "Gephyrin regulates trans-synaptic signaling at GABAergic connections in the hippocampus." Doctoral thesis, SISSA, 2010. http://hdl.handle.net/20.500.11767/4774.
Full textAbstract:
Gephyrin is the central component of the postsynaptic scaffold at inhibitory synapses, ensuring receptor accumulation in precise apposition to presynaptic release sites. Synapses are highly dynamic structures, with receptors constantly moving in and out of postsynaptic sites. The mechanisms regulating synaptic organization are thus crucial for an efficient and reliable synaptic transmission. My thesis focuses on the role of gephyrin in regulating GABAergic transmission. To study gephyrin function, I used intracellular single chain antibody fragments against
gephyrin (scFv-gephyrin) which could remove endogenous gephyrin from its subcellular location, leading to an overall loss of gephyrin clusters. Transfecting hippocampal neurons in culture with scFv-gephyrin led to a reduced density of synaptic g2-subunit containing GABAA receptors. This effect was associated with a decrease in the amplitude and frequency of mIPSCs, and a slow-down in their onset kinetics. Using an ultrafast
agonist application system which mimics synaptic events, I found that the slow onset of GABA-evoked currents was due to a slower entry of the receptors into the desensitized state. Hence, hampering gephyrin function affects the gating properties of GABAA receptors. Disruption of gephyrin clusters also altered the GABAA mediated tonic conductance, an effect that could be attributed to a reduced GABAergic innervation. Gephyrin ablation led to a reduction in the density of the vesicular GABA transporter,
VGAT. Moreover, pair recordings from interconnected neurons revealed a reduction in amplitude and in the number of successes as well as an increase in paired-pulse ratio and in the coefficient of variation of GABAA-mediated synaptic currents in scFv-gephyrin transfected neurons, indicating a reduced probability of GABA release. Gephyrin may
exert this trans-synaptic action through the neuroligin/neurexin complex. Consistent with this hypothesis, I found that upon scFv-transfection, the neuroligin isoform known to be preferentially localized at GABAergic synapses (neuroligin 2) was significantly reduced. Furthermore, in molecular biology experiments, gephyrin was found to immunoprecipitate neuroligin 2 from rat brain lysates, indicating the formation of a complex between these two proteins. Co-expression of neuroligin 2 with scFv-gephyrin was able to rescue the reduction in GABAergic innervation, suggesting that gephyrin can regulate GABA release through neuroligin 2.
Neuroligins can localize at both GABAergic and glutamatergic synapses, and modulate the excitatory/inhibitory (E/I) balance within the neuronal network. Interestingly, scFvgephyrin transfection resulted in a significant reduction in glutamatergic innervation, as revealed by the decrease in the density of the vesicular glutamate transporter, VGLUT, as well as by the reduction in the frequency of mEPSCs. Rescue experiments with the coexpression of neuroligin 2 and scFv-gephyrin did not reverse the effect of scFv-gephyrin on glutamatergic innervation, suggesting that it was not due to a homeostatic compensatory mechanism. Based on the observation that gephyrin can coimmunoprecipitate neuroligin 1 (the isoform enriched at glutamatergic synapses), it is possible that gephyrin modulates both GABAergic and glutamatergic synapses via neuroligins. However, whether gephyrin regulates glutamate release via neuroligin 1
remains to be elucidated. Overall, interfering with gephyrin clustering at the post-translational level has revealed new insights on the role of this scaffold protein in GABAergic synapses and has prompted further investigation into the function of gephyrin in regulating the E/I balance
possibly through neuroligins.
38
Pulido, Puentes María Camila. "Synaptic fluctuations in cerebellar interneurons connected by a single synaptic contact." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCB007/document.
Full textAbstract:
L’élément constitutif des synapses centrales est le site synaptique individuel, comprenant une zone active du côté présynaptique et une densité postsynaptique associée. Du fait de limitations techniques nos connaissances sur le mode de fonctionnement d’un site synaptique restent insuffisantes. Pour faire progresser cette question nous projetons d’effectuer des enregistrements en paires entre interneurones de la couche moléculaire du cervelet. Ces neurones forment des synapses qui ont des signaux élémentaires quantiques de grande taille, et les synapses comprennent parfois un seul site synaptique, ce qui fait qu’ils offrent des avantages décisifs pour ce projet. Les réponses postsynaptiques à des trains de potentiels d’action seront étudiées dans différentes conditions expérimentales. Les résultats seront interprétés par un modèle supposant que les vésicules synaptiques doivent se lier à un petit groupe de sites d’arrimage avant l’exocytoseThe unitary element of central synaptic transmission is a single synaptic site, with one active zone as presynaptic component and the postsynaptic density as postsynaptic partner. Due to technical limitations there is much uncertainty on the mode of functioning of a single synaptic site. To address this issue it is planned to perform paired recordings between interneurons of the molecular layers of the cerebellum. These neurons form synapses with a large quantal size, and occasionally displaying a single release site, and are thus favorable for this study. Postsynaptic responses will be studied in response to trains of presynaptic action potentials under various conditions. The results will be compared to a model supposing the obligatory binding of vesicles to a small complement of docking sites prior to exocytosis
39
Schümann, Anne. "Structural dynamics of GABAergic axons in the face of changing neuronal activity." Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-151839.
Full text
40
Blenau, Wolfgang, Cathleen Rotte, Jeannine Witte, Otto Baumann, and Bernd Walz. "Source, topography and excitatory effects of GABAergic innervation in cockroach salivary glands." Universität Potsdam, 2009. http://opus.kobv.de/ubp/volltexte/2010/4435/.
Full textAbstract:
Cockroach salivary glands are innervated by dopaminergic and serotonergic neurons. Both transmitters elicit saliva secretion. We studied the distribution pattern of neurons containing gamma-aminobutyric acid ( GABA) and their physiological role. Immunofluorescence revealed a GABA-immunoreactive axon that originates within the subesophageal ganglion at the salivary neuron 2 (SN2) and this extends within the salivary duct nerve towards the salivary gland. GABA-positive fibers form a network on most acinar lobules and a dense plexus in the interior of a minor fraction of acinar lobules. Co-staining with anti-synapsin revealed that some putative GABAergic terminals seem to make pre-synaptic contacts with GABA-negative release sites. Many putative GABAergic release sites are at some distance from other synapses and at distance from the acinar tissue. Intracellular recordings from isolated salivary glands have revealed that GABA does not affect the basolateral membrane potential of the acinar cells directly. When applied during salivary duct nerve stimulation, GABA enhances the electrical response of the acinar cells and increases the rates of fluid and protein secretion. The effect on electrical cell responses is mimicked by the GABA(B) receptor agonists baclofen and SKF97541, and blocked by the GABAB receptor antagonists CGP52432 and CGP54626. These findings indicate that GABA has a modulatory role in the control of salivation, acting presynaptically on serotonergic and/or dopaminergic neurotransmission.
41
Elfant, David J. "Inhibiting inhibition : GABAergic networks in the CA1 area of the rat hippocampus." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496867.
Full text
42
Ma, Ying [Verfasser]. "Effects of enhancing GABAergic transmission on sleep-associated memory consolidation / Ying Ma." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2012. http://d-nb.info/1021331007/34.
Full text
43
Chen, Jerry L. "Experience-dependent dendrite remodeling of GABAergic interneurons in the adult visual cortex." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/57993.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 85-97).
An ever increasing amount of evidence is demonstrating that structural plasticity is a diverse and ongoing feature that contributes to plasticity in the adult brain. It was previously shown that dendritic arbors of inhibitory interneurons in superficial layer 2/3 can remodel in the adult cortex. Here, we investigated the role of these structural rearrangements during experience-dependent adult plasticity. Using in vivo two photon imaging, we monitored intemeuron dendritic branch tip remodeling in response to changes in visual experience in the adult mouse visual cortex. We find that branch tip dynamics are induced by novel experiences in a stimulus-specific manner. Visual deprivation produces rearrangements that are circuit-specific and are different for branch tips extending into LI or L2/3. The weakening of dendritic input onto these cells functions to reduce levels of inhibition in local cortical circuits. This reduced inhibitory tone provides more salience to remaining instructive input, allowing more structural and functional adaptations to occur. In order to better understand how synaptic plasticity accompanies these dendritic arbor rearrangements as well as other forms of structural plasticity, we developed a method to simultaneously monitor structural and synaptic dynamics in the mammalian brain using in vivo two-photon microscopy. Structural and synaptic components can be labeled in cortical neurons of mice in a cell type and laminar specific manner through co-injection of independent lentiviral vectors at a late embryonic or early postnatal age. We demonstrate that excitatory and inhibitory post-synaptic densities can be visualized by tagging fluorescent proteins to PSD95 and Gephyrin, respectively. Finally, we show that the fluorescent proteins, Teal and Venus, can be simultaneously excited and spectrally resolved through linear unmixing so that individual structural and synaptic components can be identified and followed over time. Through this approach, the relationship between synaptic and structural plasticity can be studied in the living brain.
by Jerry L. Chen.
Ph.D.
44
Cole, Katherine L. H. "GABAergic inhibition in learning and memory : examples from the cerebellum and hippocampus." Thesis, University of Aberdeen, 2012. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192220.
Full textAbstract:
In this thesis, I describe the use of two different techniques for the targeting and functional inactivation of individual populations of GABAergic interneurons located within the cerebellum and dentate gyrus of the hippocampus. Through functional inactivation of these interneuron types, I demonstrate their behavioural relevance for the processes of learning and memory. In chapter 2, I describe a genetic approach for the removal of GABAA-mediated signalling from molecular layer interneurons (MLIs) onto Purkinje cells within the cerebellum. Using the Cre lox P system to delete post-synaptic GABAA receptors on Purkinje cells, I have shown a previously unappreciated role for MLIs in fear memory. Deficits were specific to the acquisition and long-term retention of fear memories suggesting that feed-forward inhibition from MLIs onto Purkinje cells is critical for these processes. In chapter 3, I describe a further development to this project through the creation of a novel dual recombinase mouse line. This intersectional approach of combining Cre and Flpo recombinase systems together would allow direct targeting of MLIs for the first time and circumvent drawbacks associated with using a static genetic knockout approach. In chapter 4, I describe an adeno-associated viral (AAV) approach to target a specific population of GABAergic interneurons located within the hilar region of the dentate gyrus. These hilar perforant path-associated (HIPP) cells are characterised by their expression of the neuropeptide somatostatin (SST) and regulate granule cell activity through feedback inhibition. However, up until now their behavioural relevance has been unknown. Through Cre-mediated viral expression of tetanus toxin light chain (TeLC), neurotransmission was prevented in SST interneurons revealing an involvement in spatial working memory and spatial reference memory precision. In addition, preliminary immediate early gene data suggests that SST interneurons increase memory precision through maintaining the sparse activity of the granule cell population through feedback inhibition.
45
Monsivais, Pablo. "GABAergic inhibition of nucleus magnocellularis and laminaris by the superior olivary nucleus /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/10635.
Full text
46
Jin, Xiaoming. "Dendritic development of GABAergic cortical interneurons revealed by biolistic transfection with GFP." Morgantown, W. Va. : [West Virginia University Libraries], 2002. http://etd.wvu.edu/templates/showETD.cfm?recnum=2626.
Full textAbstract:
Thesis (Ph. D.)--West Virginia University, 2002.Title from document title page. Document formatted into pages; contains vii, 218 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
47
Li, Mei. "Specification and Determination of GABAergic and Glutamatergic Neural Phenotypes in Xenopus laevis." W&M ScholarWorks, 2004. https://scholarworks.wm.edu/etd/1539626449.
Full text
48
Derera, Isabel Diane. "ALTERATIONS IN GABAERGIC NTS NEURON FUNCTION IN ASSOCIATION WITH TLE AND SUDEP." UKnowledge, 2018. https://uknowledge.uky.edu/physiology_etds/40.
Full textAbstract:
Epilepsy is a neurological disorder that is characterized by aberrant electrical activity in the brain resulting in at least two unprovoked seizures over a period longer than 24 hours. Approximately 60% of individuals with epilepsy are diagnosed with temporal lobe epilepsy (TLE) and about one third of those individuals do not respond well to anti-seizure medications. This places those individuals at high risk for sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as when an individual with epilepsy, who is otherwise healthy, dies suddenly and unexpectedly for unknown reasons. SUDEP is one of the leading causes of death in individuals with acquired epilepsies (i.e. not due to genetic mutations), such as TLE. Previous studies utilizing genetic models of epilepsy have suggested that circuitry within the vagal complex of the brainstem may play a role in SUDEP risk. Gamma-aminobutyric acid (GABA) neurons of the nucleus tractus solitarius (NTS) within the vagal complex receive, filter, and modulate cardiorespiratory information from the vagus nerve. GABAergic NTS neurons then project to cardiac vagal motor neurons, eventually effecting parasympathetic output to the periphery. In this study, a mouse model of TLE was used to assess the effect of epileptogenesis on GABAergic NTS neuron function and determine if functional alterations in these neurons impact SUDEP risk. It was discovered that mice with TLE (i.e. TLE mice) have significantly increased mortality rates compared to control animals, suggesting that SUDEP occurs in this model. Using whole cell electrophysiology synaptic and intrinsic properties of GABAergic NTS neurons were investigated in TLE and control mice. Results suggest that during epileptogenesis, GABAergic NTS neurons become hyperexcitable, potentially due to a reduction in A-type potassium channel current and increased excitatory synaptic input. Increases in hyperexcitability have been shown to be associated with an increased risk of spreading depolarization and action potential inactivation leading to neuronal quiescence. This may lead to a decreased inhibition of parasympathetic tone, causing cardiorespiratory collapse and SUDEP in TLE.
49
Kazmierczak, Marlon. "Direct Reprogramming of distinct cells into GABAergic motor neurons in C. elegans." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/19798.
Full textAbstract:
Der Gen-Knockdown mittels RNAi hat sich als essentiell erwiesen, um Inhibitoren der induzierten Transdifferenzierung in C. elegans zu identifizieren (Tursun et al., 2011). Bakterienstämme, die dsRNA exprimieren, das die Expression spezifischer Gene mindert, können dem Wurm direkt zugefüttert werden, um einen genomweiten RNAi-screen der insgesamt 20.000 Gene in C. elegans durchzuführen. Allerdings werden die meisten biologischen Prozese durch mehr als ein Gen reguliert, was den Bedarf nach einer Methode generiert, die es erlaubt, zwei oder mehr Gene gleichzeitig herunter zu regulieren, um die Steuerung biologischer Prozesse studieren zu können. Die derzeitig vorhandenen Methoden liefern entweder nicht reproduzierbare Ergebnisse oder sind nicht skalierbar. Wir nutzen baktierelle Konjugation, die es durch ein konjugatives Plasmid ermöglicht Bakterienzellen zu generieren, die zwei verschiedene RNAi-Plasmide enthalten. Das Ziel war es, modifizierte RNAi-Donor-Plasmide mittels bakterieller Konjugation an eine Vielzahl anderer Bakterienzellen zu übertragen, die bereits ein anderes RNAi-Plasmid enthalten und dies dann im Hochdurchsatzverfahren durchführen zu können. Um Enhancer induzierter Expression von unc-25::gfp in der Keimbahn, ermöglicht durch den Knockdown des Histonchaperons LIN-53 (RbAp46/48 in Menschen), zu finden, wurden RNAi-Klone generiert, die gleichzeitig lin-53 als auch eines von insgesamt 800 verschiedenen Chromatin-bezogenen Gene herunter regulieren. Dabei identifizierten wir RBBP-5, Mitglied des Set1/ MLL-Methyltransferase-Komplexes, als neuen Barrierefaktor der induzierten Transdifferenzierung. RBBP-5 agiert dabei mutmaßlich parallel zu LIN-53. Doppelte RNAi, ermöglicht durch bakterielle Konjugation, erlaubt den simultanen Knockdown zweier oder mehr Gene, um genetische Interaktionen studieren zu können und erweitert damit die Einsatzmöglichkeiten von RNAi-Screens, um untereinander verbundene biologische Prozesse zu studieren.The knock down of genes by RNAi has been fundamental to identify inhibitors of induced cell transdifferentiation in C. elegans (Tursun et al., 2011). Bacteria strains expressing dsRNA that target specific genes can be fed to the worm allowing straightforward whole-genome RNAi screens of the 20,000 genes in theC. elegans genome. However, many biological processes are regulated by more than one gene raising the need for simultaneous knock down of two or more genes to more fully interrogate the regulation of complex biological processes. Two approaches are currently available for double RNAi knockdown, − two bacteria strains expressing specific dsRNA can be mixed and grown together and fed simultaneously, which gives highly variable results. Alternatively, a new bacterial clone can be generated carrying a plasmid on which two RNAi targets of interest are 'stitched' together, which is not scalable. To address this challenge, we have developed a protocol using bacterial conjugation mediated by the 'Fertility Factor' (F) Episome in order to combine two different RNAi plasmids in a single bacterium. The objective was to be able to transfer a single RNAi plasmid to a large number of bacterial cells carrying different RNAi clones in one step in a high-throughput manner for large scale 'double' or even 'triple' RNAi screens. To find enhancers of induced unc-25::gfp expression in the germ line enabled by the depletion of histone chaperone LIN-53 (RbAp46/48 in humans), double RNAi clones targeting lin-53 and a total of 800 chromatin-related genes were generated and screened. We identified the Set1/MLL methyltransferase complex member RBBP-5 as a novel reprogramming barrier that putatively acts in a parallel pathway to LIN-53. Double RNAi by conjugation permits to reliably knock down two genes simultaneously in order to study genetic interactions at a genome-wide level, thus further increasing the versatility of RNAi screens to investigate interconnected biological processes.
50
Antonelli, Roberta. "The role of prolyl-isomerase PIN1 in GABAergic and glutamatergic synaptic transmission." Doctoral thesis, SISSA, 2015. http://hdl.handle.net/20.500.11767/4893.
Full textAbstract:
The correct functioning of the central nervous system relies on the rapid and efficient communication between neurons. This occurs at highly specialized functional points of contact called synapses. Synapses are extremely plastic in structure and function, strongly influenced by their own histories of impulse traffic and by signals from nearby cells. Synaptic contacts are fundamental to the development, homeostasis and remodeling of neural circuits. All these events are achieved through different mechanisms operating at both pre- and postsynaptic sites. At the level of the post synaptic density (PSD) compartment, scaffolding molecules and trans-membrane proteins are known to orchestrate proper synapses formation, maturation and rearrangement required to sustain plasticity processes.
Protein phosphorylation represents one of the most important mechanisms engaged in affecting the molecular composition of the post-synaptic device. Most studies have focused on the impact of phosphorylation on the gating properties, surface mobility and trafficking of neurotransmitter receptors while much less is known about the effect of post-translational modifications on scaffolding and cell adhesion molecules functionally linked to neurotransmitter receptors.
At GABAergic synapses specific phosphorylation events of the scaffolding molecule gephyrin were shown to alter its multimerization properties, thus producing parallel changes in the number of receptors trapped by the scaffold leading to alterations of synaptic strength. Most of these phosphorylation events occur at serine or threonine residues preceding a proline, underlying a potential role of proline-directed phosphorylation as modulator of synaptic strength. The key player of such signalling cascade is represented by a small enzyme called peptidyl-prolyl isomerase Pin1 (protein interacting with NIMA 1). Pin1, upon recruitment by its substrates in a phosphorylation-dependent manner, catalyzes the cis/tran isomerization of phospho‐Ser/Thr‐Pro motifs leading to changes in target protein conformation and biological activity. Pin1 is highly expressed in neurons suggesting that it can exert a crucial role in synaptic transmission and plasticity processes at both inhibitory and excitatory synapses.
In the first part of my PhD thesis I focused on the impact of Pin1-dependent signalling on GABAergic transmission. I found that the cell adhesion molecule of the neuroligin family enriched at GABAergic synapses, Neuroligin 2 (NL2), undergoes post-phosphorylation prolyl-isomerization modulation of its activity. Using biochemical approaches I found that the unique Pin1 consensus motif present within the cytoplasmic tail of NL2, Serine 714-proline, is indeed phosphorylated in vivo. Proline-directed phosphorylation at Serine 714 of NL2 strongly impacts on NL2 ability to complex with gephyrin. In particular, at this site, post-phosphorylation prolyl-isomerization negatively regulates the ability of NL2 to interact with gephyrin. In line with biochemical results, immunocytochemical analysis reveal that, in the absence of Pin1 expression, NL2/gephyrin complexes are enriched at GABAergic post-synaptic sites and this enrichment is accompanied by an enhanced synaptic recruitment of GABAA receptors (GABAAR). This effect was associated with a concomitant increase in the amplitude, but not in frequency, of spontaneous inhibitory post-synaptic currents (IPSCs). These findings unveil the existence of a new signalling pathway operating at inhibitory GABAergic synapses able to alter the efficacy of GABAergic transmission by modulating NL2/gephyrin interaction.
Given the high abundance of Pin1 at excitatory synaptic contacts, in the second part of my PhD thesis I focused on the impact of Pin1-dependent signalling on excitatory glutamatergic transmission. In particular, I started to investigate whether the scaffolding molecule PSD-95, a member of the Disc-Large (DGL)-Membrane-associated guanylate kinase, could be a target of Pin1-dependent signalling cascade. I observed that Pin1, known to reside in post-synaptic structures, is recruited by PSD-95 at specific Serine-Threonine/Proline consensus motifs localized in the linker region connecting PDZ2 to PDZ3 domains. These sites are represented by Treonine287-Proline, Serine290-Proline and Serine295-Proline, and deletion of all of them almost completely abolished Pin1 interaction with PSD-95. Pin1 exerts a negative control on PSD-95 ability to complex with N-Methyl-D-Aspartate receptors (NMDARs). Indeed an enhanced PSD-95/NMDAR complex formation was detected in brain extracts derived from Pin1-/- mice. In electrophysiological experiments, larger NMDA-mediated synaptic currents were detected in CA1 principal cells in hippocampal slices obtained from Pin1-/- mice as compared to controls, an effect that was associated with an enhancement in spine density and size.
These data indicate that Pin1 controls the synaptic content of NMDARs via PSD-95 prolyl-isomerization and the expression of dendritic spines, both required for the maintenance of long-term potentiation.
Overall, this study highlights the crucial role of Pin1-dependent signalling in the functional organization of both inhibitory and excitatory synapses.