Dissertations / Theses on the topic 'Substanita nigra'
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1
Boyes, Justin. "The microcircuitry of the substantia nigra." Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408818.
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Fan, Xiu-Di. "Substantia nigra dopamine infusion, behavioral and biochemical correlates." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ32783.pdf.
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Häusser, Michael. "Intrinsic properties and synaptic inhibition of substantia nigra neurones." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306691.
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Richards, Christopher David. "Electrophysiology and electrochemistry of substantia nigra neurones in vitro." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259895.
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Barstow, Karen L. "Subthalamic control of dopamine release in the substantia nigra." Thesis, Boston University, 2001. https://hdl.handle.net/2144/36754.
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Thesis (Ph.D.)--Boston UniversityPLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
The overall goal of this dissertation was to determine the role of the subthalamic nucleus (STN) in regulating the release of dopamine in the substantia nigra (SN). Experiments first established the existence of a direct connection between subthalamic neurons and SN dopaminergic cells. Further experiments showed that this connection triggers the dopamine release in the SN, and the mechanisms involved in this release were determined. Whole-cell current clamp recordings were performed in parasagittal brain slices obtained from 10 to 16 day-old rat pups. Electrical stimulations of the STN reliably triggered excitatory post-synaptic potentials (EPSPs) in dopaminergic neurons of the SN pars compacta (SNc). Pharmacological experiments with specific receptor antagonists indicated that this EPSP was mediated by NMDA, non-NMDA and metabotropic glutamate receptors. Stimulations of the subthalamic input triggered the release of dopamine. In a subset of neurons in the SN pars reticulata (SNr), repetitive stimulations of the STN produced a summating EPSP that was followed by an inhibitory postsynaptic potential (IPSP). A D2 receptor antagonist blocked this IPSP suggesting that it represents the D2 receptor-mediated response of the recorded cell to dopamine released upon stimulation of the STN. Pharmacological experiments using this assay indicated that NMDA, non-NMDA or metabotropic glutamate receptors were individually not required for dendritic release of dopamine; however, each contributed to this release. In dopaminergic neurons located in the SN pars compacta, the inhibitory effect of dopamine was revealed following block of L-type Ca channels, NMDA and non-NMDA glutamate receptors. These results indicated that dopaminergic neurons located both in the SNc and SNr respond to the dendritic release of dopamine triggered upon stimulations of the STN. Finally, a specific blocker of the dopamine transporter (GBR12935) blocked the IPSP reversibly in both SNr and SNc dopaminergic neurons. If release occurred by exocytosis, block of the transporter should increase extracellular levels of dopamine and produce an increase in the size of the recorded IPSP. Therefore, these results suggest that dopamine dendritic release triggered by activation of the subthalamic input was mediated by reversed transport of dopamine rather than by exocytosis.
2031-01-01
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McCormack, Alison. "The non-human primate as a model of human parkinsonism /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-624-7/.
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Last, A. T. J. "An electrophysiological study of neurochemical interactions in the substantia nigra." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.382628.
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Threlfell, Sarah. "The histaminergic regulation of serotonin release in the substantia nigra." Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432289.
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Hallett, James Matthew. "Evidence for GluN3-containing receptors in rat substantia nigra neurones." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607886.
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Fearnley, Julian Michael. "Regional substantia nigra selectivity in the pathology of movement disorders." Thesis, University College London (University of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319957.
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Batista, Carla Isabel Soares. "Regulação dos níveis de GDNF na substantia nigra pelo estradiol." Master's thesis, Universidade de Aveiro, 2007. http://hdl.handle.net/10773/731.
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Mestrado em ToxicologiaO stress oxidativo ao nível da via nigroestriatal é reconhecido como uma das causas da degeneração dos neurónios dopaminérgicos da substantia nigra na doença de Parkinson (DP), sendo o efeito protector do estradiol recorrentemente associado à protecção contra o stress oxidativo. A acção protectora do estradiol na via nigroestriatal pode ainda envolver outros efeitos, tais como modulação da expressão de factores neurotróficos cuja capacidade de promover a sobrevivência neuronal é sobejamente conhecida. Neste trabalho analisámos a regulação dos níveis do factor neurotrófico derivado de uma linha de células da glia (GDNF) pelo 17β-estradiol na substantia nigra e determinámos qual a contribuição específica deste efeito para a acção neuroprotectora da hormona. Adicionalmente, estudámos a modulação do efeito do 17β-estradiol na expressão de GDNF por agentes oxidantes, levodopa (L-DOPA) e H2O2. Para determinar os níveis de GDNF procedemos a análise de Western-Blot em extractos de células pós-natais de substantia nigra em cultura após incubação com 17ß-estradiol. Realizámos estudos in vivo para determinar de que forma o 17ß-estradiol afecta a acção da toxina dopaminérgica 6-hidroxidopamina (6-OHDA), quer ao nível da viabilidade das células dopaminérgicas, como ao nível da expressão dos níveis de GDNF. Os resultados obtidos permitiram concluir que, em células pós-natais de substantia nigra em cultura, o 17ß-estradiol promoveu o incremento da expressão do GDNF pelos astrócitos, provavelmente via ligação a receptores membranares. Verificámos ainda que os efeitos do estradiol parecem ser potenciados pela a exposição a L-DOPA e H2O2. In vivo, o estradiol protegeu as células dopaminérgicas da substantia nigra da lesão causada por 6-OHDA, possivelmente através da estimulação da síntese de GDNF observada nestas condições. ABSTRACT: Estradiol is currently considered a neuroprotector agent of nigral dopaminergic neurons. Oxidative stress in the nigrostriatal pathway has been associated with the development of Parkinson disease and the protective effect of estradiol is thought to be associated with a defence against oxidative stress. The protection promoted by estradiol in nigrostriatal pathway may also be coupled to the expression of neurotrophic factors, molecules recognized by its capability to promote neuron survival. In this study we analysed how 17ß-estradiol regulates nigral glial cell line deriv GDNF levels and evaluated the contribution of this effect to the neuroprotective action of this hormone. We also assessed how levodopa (L-DOPA) and H2O2 modulated the effect of estradiol on GDNF expression. Western-Blot analysis was used to determine GDNF levels in cultured substantia nigra cells after incubation with 17ß-estradiol. Using in vivo studies we evaluated how 17ß-estradiol affects the action of the dopaminergic toxin - 6- hidroxydopamine (6-OHDA) on the dopaminergic cell viability and the expression of GDNF. Taken together the results showed that, in cultured postnatal substantia nigra cells, 17ß-estradiol promoted the increase of GDNF expression by astrocytes through activation of putative membrane receptors. Exposure to the oxidative agents L-DOPA and H2O2 augmented the effect of estradiol. In vivo, estradiol protected nigral dopaminergic cells from 6-OHDA induced injury, possibly through stimulation of GDNF synthesis.
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Hicks, Gareth A. "Adenosine 5'-triphosphate-sensitive potassium channels in the rat substantia nigra." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321402.
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O'Callaghan, John Francis Xavier. "Mechanisms in neurochemical modulation in the substantia nigra : an electrophysiological study." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260149.
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Johnson, Otto Luke Ross. "Physiological and anatomical control of burst firing in the substantia nigra." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268205.
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Kapoor, Raju. "Studies of in vitro preparations of the cerebellum and substantia nigra." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.480555.
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Yung, Wing Ho. "Physiology and morphology of substantia nigra pars compacta neurones in vitro." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280920.
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Wild, Angela. "Regulation of NMDA receptors in substantia nigra pars compacta dopaminergic neurones." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608146.
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Brothwell, Shona Lindsay Crawford. "Properties of NMDA receptors in Substantia nigra pars compacta dopaminergic neurones." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612352.
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Zhao, Q. "Activation properties and pharmacology of NMDA receptors in rat substantia nigra." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1386599/.
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In this thesis i have used patch-clamp single channel and whole-cell recordings to quantify the properties of NMDA receptors in pars compacta of the substania nigra (SNc) dopaminergic neurons. NMDA receptors are ubiquitously expressed in the central nervous system and are generally composed of two glycine-binding GIuN1 subunits and two glutamate binding GIuN2 subunits. While many receptors are diheteromers of GluN1 and a single type of GiuN2 subunit, there is evidence for triheteromeric GIuN1/GIuN2B/GIuN2D receptors in the midbrain and cerebellum. Results suggest NMDA receptor activation in SNc dopaminergic neurons produces bursts of channel openings, which combined with the first latencies to activation, generate the familiar slowly rising and decaying macroscopic NMDA response. A modification to a standard kinetic model of NMDA receptor activation (the Banke & Traynelis model) was found to adequately fit the low NMDA concentration single channel data and the rate constants from this fitting predicted a macroscopic response to a brief pulse of 1 mM NMDA that was similar to that observed in concentration jump experiments. The co-localization of kinetically distinct GIuN2B and GIuN2D subunits in a single triheteromeric GluN1/GluN2B/GiuN2D receptor may account for the combination of pharmacological and kinetic properties observed in these experiments for NMDA receptors from the rat substantia nigra.
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Wright, Kristina M. "Revising the Role of the Ventrolateral Periaqueductal Gray in the Fear Circuit:." Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109159.
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Thesis advisor: Michael A. McDannaldThesis advisor: John P. Christianson
The ability to accurately evaluate and respond to threats is vital to survival. Disruptions in neural circuits of fear give rise to maladaptive threat responding, and have clinical implications in fear and anxiety disorders. To better inform therapeutic interventions, it is imperative that roles for regions classically associated with fear continue to be refined, and that novel nodes are incorporated into what is most certainly a larger fear circuit. In the canonical view, threat estimates are generated at the level of the amygdala and sent to the ventrolateral periaqueductal gray (vlPAG), which organizes an appropriate behavioral response, most notably freezing. Despite a multitude of studies successfully linking the vlPAG and Pavlovian fear behavior, evidence of a direct neural correlate for fear expression in the vlPAG is lacking. By contrast, a role for the caudal substantia nigra (cSN) in fear, stands apart from its canonical associations with movement and reward processes. Although there is new interest in examining a role for the nigra in fear modulation, this is essentially an uncharted area of discovery. The goals of this dissertation are three-fold. First, to propose a role for vlPAG activity in threat estimation, a function previously restricted to the upstream amygdala. Second, to scrutinize vlPAG neural activity using a novel multi-cue Pavlovian procedure and identify the long-anticipated, direct neural correlate for fear expression. Third, to present causal evidence supporting the cSN as a potential node in a circuit that most certainly extends beyond regions canonically associated with fear
Thesis (PhD) — Boston College, 2021
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Psychology
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葉天恒 and Tin-hang James Yip. "Emotion recognition in patients with Parkinson's disease: contribution of the substantia nigra." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227016.
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Kingsbury, Ann Elizabeth. "In situ hybridization studies of human substantia nigra : pathophysiology of Parkinson's disease." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398427.
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Yip, Tin-hang James. "Emotion recognition in patients with Parkinson's disease : contribution of the substantia nigra /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24873007.
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Feddersen, Berend. "Contrôle des crises épileptiques par les ganglions de la base : approches expérimentale et clinique." Grenoble 1, 2009. http://www.theses.fr/2009GRE10111.
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Près de 30% des patients qui souffrent d´une épilepsie sont résistants aux traitements pharmacologiques et seuls 30% de ces patients peuvent bénéficier d'une alternative thérapeutique par résection chirurgicale. La recherche de cibles et stratégies thérapeutiques innovantes constitue un enjeu majeur pour la prise en charge de ces patients. De nombreuses études expérimentales chez l'animal indiquent que les ganglions de la base, et en particulier la substance noire, exercent un contrôle sur la survenue des crises d'épilepsie. Des arguments cliniques, obtenus par électrophysiologie ou imagerie médicale, sont également en faveur de la mise en jeu des ganglions de la base dans certains syndromes épileptiques. Chez des patients souffrant d'épilepsie focale, l'influence de la propagation des crises au travers des ganglions de la base a été examinée en rapport avec le taux de généralisation secondaire. Chez ces patients l'activation des ganglions de la base semble associée à une influence inhibitrice sur la propagation des crises lorsque celles-ci envahissent le lobe frontal. L'exploration de ces mécanismes inhibiteurs des crises est susceptible d'ouvrir de nouvelles perspectives thérapeutiques comme celle portant sur la stimulation intracérébrale profonde. Les premières études de cas explorant les effets de la stimulation intracérébrale des ganglions de la base chez quelques patients ont permis d'obtenir des résultats encourageants chez certains d'entre eux. Cependant de nombreuses études précliniques devraient permettre de préciser les paramètres de stimulation à appliquer. Une approche expérimentale chez l'animal nous a permis de déterminer les paramètres optimaux à appliquer pour controler la survenue de crises spontanées dans un modèle d'épilepsie-absence chez le rat. Dans ce modèle les paramètres optimaux à appliquer à la substance noire réticulée consistent en des stimulations bilatérales, bipolaires, monophasiques, de 60 Hz en fréquence et de 60 µs en largeur d'impulsion. Appliqués de façon répétée, ces paramètres ne permettent cependant pas de supprimer durablement la survenue des crises et ont même tendance à augmenter le nombre de crises enregistrées. Un délais d'au moins 60 seconde entre l'application de deux stimulations consécutives est à respecter pour interrompre les crises. Dans nos conditions, bien qu'une stimulation haute-fréquence de la substance noire réticulée appliquée de façon aigue puisse interrompre une crise en cours, des stimulations répétées semblent inefficaces. Ceci est en faveur du développement en cours, dans de nombreux laboratoire à travers le monde, de procédures de stimulation des crises asservie à leur détection afin de les supprimer de façon chronique dans le cadre d'applications thérapeutiques. De tels systèmes, dits « adaptatifs », seront particulièrement pertinents s'ils sont couplés à des modifications détectables, signalant l'arrivée d'une crise. Dans le modèle d'épilepsie-absence chez le rat, de telles modifications ont été identifiées au niveau de la cohérence entre signaux électroencéphalographiques issus des deux substances substances noires réticulées. Ces modifications pourraient etre utilisées comme signature spécifique de l'imminence d'une crise dans le couplage de la stimulation à la détection des crises. Toutefois, rien ne permet de dire si ces modifications sont spécifiques du modèle etudié ou encore si de telles modifications existent dans certains syndromes épileptiques en clinique. De nombreux arguments existent pour dire que l'épilepsie n'est pas une pathologie restreinte au seul cortex en tant que circuit générateur de crises, mais implique également des structures sous-corticales susceptibles d'exercer un contrôle à distance sur les circuits générateurs de crises. Cette conception de l'épilepsie permet d'envisager le développement de nouvelles stratégies thérapeutiques pour les patients pharmaco-résistants et qui ne peuvent pas bénéficier d'une intervention chirurgicaleAs about one third of epileptic patients are resistant to antiepileptic drugs, and only 30% of them are candidates for resective surgery, it exists a great demand for the development of alternative surgical therapies. It has been shown in animal studies, that the basal ganglia and especially the substantia nigra (SN) are involved in the control of epilepsy. Clinical evidence, using either electrophysiological or imaging approaches, also supports the involvement of the basal ganglia in some epileptic syndromes. The influence of seizure spread into the basal ganglia in patients with focal epilepsies was investigated on the rate of secondary generalization. We showed that activation of the basal ganglia was associated with an inhibitory effect on seizure propagation, when seizures spread into the frontal lobe. The elucidation of inhibitory mechanisms in epilepsy may open a new approach for therapeutic strategies such as electrical deep brain stimulation. First open case series, investigating deep brain stimulation of the basal ganglia to suppress epileptic seizures, showed encouraging results in some patients. However, more preclinical studies are mandatory to investigate the optimal stimulation parameters. The aim of our experimental approach was to determine the optimal stimulation parameters to control spontaneous seizures in a genetic model of absence epilepsy in the rat. In this model, the optimal parameters of single substantia nigra pars reticulata (SNr) stimulation were determined as bilateral, bipolar, monophasic, 60 Hz frequency and 60 µs pulse width. When these parameters were used for repeated stimulations, no long-term suppression and even increase of the number of seizures was observed. A delay of at least 60 sec was necessary between stimulations to be fully effective. Although single high-frequency stimulation of the SNr can be used to suppress ongoing seizures, repeated stimulation are ineffective and could even aggravate seizures, thus supporting the need of closed-loop stimulation procedures to chronically suppress seizures in therapeutical applications. Such an adaptative device would be effective only when detectable changes heralds the seizure onset. In a genetic model of absence epilepsy such changes in the EEG-coherence between the left and right SNr could be identified. Such changes might be used as an hallmark for adaptative procedures like triggered single stimulation to avoid the occurrence of the presumed seizures. To date it remains unknown, if such changes in coherence between left and right SNr, are specific to the model of GAERS and if such changes occur also in other animal models or humans with different epileptic syndromes. Accumulating evidences support that epilepsy is not a pathology restricted to the cortex as a seizure generator, but that subcortical structures are also involved, which might open new therapeutic options for patients who are pharmacoresistant and no candidates for a resective surgical treatment
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Brown, Matthew Thomas Clifford. "Electrophysiological Neurochemical and morphological characterisation of the dopaminergic neurons in the substantia Nigra." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504319.
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Fathinia, Panteha [Verfasser]. "Die Bedeutung der Hyperechogenität der Substantia nigra bei der Amyotrophen Lateralsklerose / Panteha Fathinia." Ulm : Universität Ulm, 2018. http://d-nb.info/1166757145/34.
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Farrant, M. "Inhibitory neurotransmission and amino acid release in the substantia nigra of the rat." Thesis, University College London (University of London), 1987. http://discovery.ucl.ac.uk/57623/.
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Falkenburger, Björn Henrik. "Freisetzung von Dopamin aus Dendriten dopaminerger Neurone der Substantia nigra durch den Dopamin-Transporter." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=965704343.
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Duke, Dawn. "Expression profiling of the parkinsonian substantia nigra : towards a molecular defination of regional vulnerability." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497503.
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Kimm, Tilia. "Potassium and Sodium Currents Regulating Pacemaking and Burst Firing in Substantia Nigra Dopamine Neurons." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:14226104.
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Dopamine-releasing neurons with cell bodies in the substantia nigra pars compacta (SNc) are a primary source of dopamine in the mammalian brain. Dysfunction of dopaminergic signaling
is associated with numerous psychiatric disorders, and degeneration of the SNc is one of the
hallmarks of Parkinson’s disease. These neurons are autonomous pacemakers. Their spontaneous
action potentials supply target areas with baseline dopaminergic tone, while synaptically-triggered bursts signal salient events. My goal was to understand the ionic currents that regulate spontaneous and burst firing in these neurons, using acutely dissociated somata from mouse SNc.
Little is known about the potassium channels that participate in action potential repolarization in SNc neurons. Chapter 2 describes major complementary contributions of large conductance calcium-activated potassium (BK) channels and voltage-gated Kv2 channels. Inhibiting
either type of channel individually had little effect on pacemaking because the resulting small spike broadening recruited more current through the other type and because there is a functional “reserve” of both types. In contrast, these channels regulate evoked burst firing in distinct ways: the frequency of evoked firing was increased by inhibition of Kv2 channels but decreased by inhibition
of BK channels. The opposing effects on burst firing can be understood through the different channel kinetics, with BK channels activating and deactivating much faster than Kv2 channels.
Sodium channels are critical components of action potential generation. Current models of SNc firing rely on sodium channel data obtained at reduced temperatures using non-physiological solutions. Chapter 3 describes characteristics of voltage-gated sodium channels in SNc neurons at 37°C using physiological ionic conditions. Based on these results, we constructed a computational model of voltage-gated sodium channels and explored how their gating helps regulate both
pacemaking and burst-like firing.
A variety of peptide toxins have been critical for separating currents carried by particular ion channels in central neurons. Chapter 4 describes the surprising observation that SNX-482,
commonly used as a specific inhibitor of R-type Cav2.3 channels, is actually even more potent as an inhibitor of A-type potassium current in SNc neurons. Further experiments using transfected HEK-293 cells revealed that SNX-482 inhibits both Kv4.3 and Kv4.2 channels.
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Keegan, Karl David. "Analysis of neurotensin and tachykinin receptor-mediated responses in the rat substantia nigra, in vitro." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282000.
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Röben, Benjamin [Verfasser], and Daniela [Akademischer Betreuer] Berg. "Hyperechogenität der Substantia nigra : Prävalenz und Assoziation mit kardiovaskulären Risikoprofilen / Benjamin Röben ; Betreuer: Daniela Berg." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1198120274/34.
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Morris, Paul George. "Functions of GluN2D-containing NMDA receptors in dopamine neurons of the substantia nigra pars compacta." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271850.
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Dopamine (DA) neurons of the substantia nigra pars compacta (SNc) have a key role in regulation of voluntary movement control. Their death is a hallmark of Parkinson’s disease, characterised by inhibited motor control, including muscle rigidity and tremor. Excitatory input to SNc-DA neurons is primarily from the subthalamic nucleus, and in PD these afferents display a higher frequency firing, as well as increased burst firing, which could cause increased excitatory activity in SNc-DA neurons. NMDA receptors (NMDARs) bind the excitatory neurotransmitter glutamate, and are essential for learning and memory. In SNc-DA neurons, NMDARs have a putative triheteromeric subunit arrangement of GluN1 plus GluN2B and/or GluN2D. Wild type (WT) mice, and those lacking the gene for GluN2D (Grin2D-null), were used to explore its role in various aspects of DA neuronal function and dysfunction using patch-clamp electrophysiology, viability assaying, and immunofluorescence. Pharmacological intervention using subunit-specific inhibitors ifenprodil and DQP-1105 on elicited NMDAR-EPSCs suggested a developmental shift from primarily GluN2B to GluN2B/D. Activity dependent regulation was assessed by high frequency burst stimulation of glutamatergic afferents: in comparison to controls, significant downregulation of NMDARs was observed in SNc-DA neurons, though no differences were observed based on genotype. This regulatory function may be a neuroprotective or homeostatic response. Ambient extracellular glutamate elicits tonic NMDAR activity in SNc-DA neurons, which may be important for maintaining basal levels of excitability: the role of GluN2D was assessed by recording the deflection in baseline current caused by application of competitive NMDAR antagonist D-AP5. There was a significantly larger NMDAR-mediated current in WT vs Grin2D-null mice, indicating that GluN2D has a role in binding ambient glutamate. Dysfunction of glutamate uptake could be a secondary pathophysiological occurrence in the SNc, leading to increased ambient glutamate: the effect of this was explored by application of the competitive glutamate transporter blocker TBOA. Here, the NMDAR-mediated portion of this current was significantly higher in WT mice in comparison to Grin2D-null. Interestingly, dose-response data obtained from bath application of NMDA showed significantly larger currents in Grin2D-null animals vs WT, but only at the top of the response curve (~1-10 mM), which may indicate a capability for larger conductance in Grin2D-null animals at high NMDAR saturation due to replacement of GluN2D with GluN2B. GluN2D may therefore be neuroprotective, by attenuating peak current flow in response to very high agonist concentrations. Lastly, GluN2D has been found to decrease NMDAR open probability under hypoxic conditions, potentially conferring resistance to hypoxia / ischemia related excitotoxicity. Therefore, low (15% O2 / 80% N2 / 5% CO2) vs high (95% O2 / 5% CO2) oxygen conditions were used along with immunofluorescent propidium iodide cell death assaying and immunofluorescent labeling for DA neurons in order to compare levels of DA neuronal death in the SNc based on oxygen status and genotype. Whilst there was a significant submaximal effect based on O2 status, genotype did not confer a practical resistance under these conditions. In summary, NMDARs have diverse roles in SNc-DA neurons which may both serve to maintain normal function and protect the cell against potentially pathological conditions.
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Töllner, Kathrin. "Die Bedeutung der Substantia nigra pars reticulata für die Temporallappenepilepsie pharmakologische Manipulation und elektrophysiologische Messung." Giessen DVG-Service, 2009. http://library.vetmed.fu-berlin.de/ResourceList/details/202703.
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CARDOSO, Henriqueta Dias. "Mecanismos neuroquímicos envolvidos na neurodegeneração da Substantia nigra pela restrição dietética em ácidos graxos essenciais." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/13273.
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Os ácidos graxos essenciais (AGEs) têm sido indicados como potenciais agentes preventivos e terapêuticos em uma grande variedade de doenças neurodegenerativas assim como indispensáveis para o desenvolvimento cerebral. O principal objetivo deste trabalho foi investigar os mecanismos relacionados com a perda de neurônios dopaminérgicos induzida pela deficiência crônica em AGEs previamente detectada na substância negra (SN) de ratos Wistar jovens (J), estendendo a análise também a animais adultos (A). Para isso, foram utilizadas dietas balanceadas e que diferiram apenas na fonte lipídica, sendo óleo de soja para os grupos controles (C) e óleo de coco para os grupos experimentais (E). As dietas foram fornecidas às mães a partir do acasalamento e mantidas por uma (F1) ou duas (F2) gerações. Marcadores de insulto oxidativo: lipoperoxidação (LP), atividade das enzimas superóxido dismutase total (SOD-t), catalase (CAT) na SN e corpo estriado (CE) foram avaliados em animais AF1 e em JF2 e AF2. Indicadores de neurodegeneração na SN e CE destes animais foram avaliados utilizando a técnica de marcação com o fluoróforo, Fluoro Jade C. Análise quantitativa do tamanho e nº de neurônios dopaminérgicos e da distribuição de células imunorreativas ao fator neurotrófico derivado do cérebro (BDNF) foi realizada em animais AF2. Os níveis de nitrito, como indicador da produção de óxido nítrico na SN e CE, foram analisados em animais JF2 e AF2. A dieta experimental reduziu em ~28%, ~50% e ~60% os níveis de ácido docosahexaenóico (DHA) na SN dos grupos experimentais AF1, JF2 e AF2 respectivamente, comparado aos seus controles. Nos animais EAF1 um aumento em ~17% e ~45% na atividade da SOD-t foi observado na SN e CE comparado ao grupo controle, o evitou níveis danosos de lipoperoxidação. Por outro lado, um aumento nos níveis de lipoperoxidação (~34%) foi detectado na SN de animais EJF2, acompanhados de não reatividade da SOD-t e de uma redução em 4,8 vezes na atividade da CAT. Sinais de neurodegeneração foram evidenciados em neurônios dopaminérgicos e não dopaminérgicos da SN do grupo EJF2. No CE, o aumento da LP em ~39% foi acompanhado de redução em 3,8 vezes e 2,8 vezes da atividade da SOD-t e CAT, respectivamente, só foram observados nos animais do grupo EAF2. A dieta experimental não alterou os níveis de nitrito na SN, mas aumentou de forma significativa estes níveis no CE de animais jovens (30%) e adultos (1,8 vezes). A deficiência crônica em DHA até a idade adulta comprometeu o crescimento do corpo celular e aumentou a perda de neurônios dopaminérgicas na SN rostro-dorso-medial (~35%) afetando também aqueles localizados na região caudo-ventro-lateral deste núcleo. Uma redução de ~22% no número de células BDNF+ foi também observada na SN. Os resultados mostram que a restrição dietética em AGEs por duas gerações até a idade adulta é capaz de induzir lipoperoxidação na SN e CE devido a comprometimento na atividade das enzimas anti-oxidantes, perda de células BDNF+ na SN e aumentados níveis de óxido nítrico no CE. Tidos em conjunto, tais mecanismos podem estar atuando de forma sinérgica na degeneração de neurônios dopaminérgicos induzida pela deficiência em DHA.
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Ghorayeb, Imad. "Initiation d'analogues expérimentaux de la dégénérescence striatonigrique." Bordeaux 2, 2001. http://www.theses.fr/2001BOR28890.
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La dégénérescence striatonigrique (DSN est une maladie neurodégénérative grave caractérisée par un syndrome parkinsonien dopa-résistant dû à l'atteinte combinée de la substance noire compacte (SNc) et du striatum. Le développement d'analogues expérimentaux reproduisant les conditions anatomiques de cette maladie offre l'opportunité d'étudier les modifications motrices et leur physiopathologie. Nous avons démontré la faisabilité de tels analogues expérimentaux à la fois chez le rongeur et pour la première fois chez le primate non-humain. Pour ceci, nous avons combiné une liaison striatale avec une lésion nigrale chez le rat, en utilisant uns stratégie stéréotaxique de "double toxine - double lésion" avec l'acide quinolinique (AQ) et la 6-OHDA, et de "toxine unique-double lésion" avec le MPP+. Chez le primate non humain, nous avons utilisé une stratégie systémique par injections séquentielles et chroniques de MPTP et d'acide 3-nitropropionique (3NP). Les résultats obtenus chez le rongeur plaident en faveur d'un dysfonctionnement moteur "spécifique" au groupe atteint de la double lésion (AQ + 6-OHDA). Ce dysfonctionnement apparaît différent de celui obtenu par une lésion striatale unique (groupe AQ) ou par une lésion seule de la SNc (groupe 6-OHDA). Chez le primate, l'aspect clinique le plus marquant était le développement successif d'un syndrome parkinsonien dopa-sensible puis dopa-résistant. Ce dernier était associé à une perte des neurones des deux voies de sorties striatalres, similaire à celle observée dans la DSN. Au total, nous avons montré que le syndrome moteur et les lésions anatomiques de la DSN pouvaient être reproduits à la fois chez le rongeur et chez le primate. Ceci nous permettra de développer à terme de nouvelles stratégies thérapeutiques (neuroprotection, neurorestauration et stimulation cérébrale profonde) dans cette maladie actuellement dépourvue de traitement efficaceL-Dopa-unresponsive parkinsonism dominates the clinical syndrome of striatonigral degeneration (SND), a severe neurodegenerative disease which is caracterized by a dual pathology affecting nigral dopaminergic neurons and striatal output neurons. Experimental models reproducing salient pathological features are needed to better understand the underlying pathophysiology of motor signs and dopa-unresponsiveness. We demonstrated the feasibility of such models in rodents as well as, and for the first time, in non-human primates. In rodents, a "double toxin-double lesion" using quinolinic acid (QA) + 6-OHDA and a "single toxin-double lesion" stereotaxic approache using MPP+ were explored, while in non-human primates systemic and sequential chronic MPTP + 3-nitropropionic acid (3NP) injections was used. In rodents, "specific" motor symptoms were induced by the combined striatal and nigral lesion that were different from those induced by a single striatal or nigral lesion. In primates, the most relevant clinical aspect is the subsequent occurence of a L-Dopa-responsive then of a L-Dopa-unresponsive parkinsonism. The latter was associated with a decreased density of dopaminoceptive medium spiny neurons of both the indirect and direct striatal outflow pathways as observed in SND. Altogether, our results clearly demonstrate that basic SND clinical and pathological features can be reproduced in rodents as well as in non-human primates. These models will be helpful for exploring new therapeutics strategies (neuroprotection, neurorestoration, deep brain stimulation) prior to clinical applications
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Bouyssières, Céline. "Induction de signaux calciques dans les cellules gliales de la substance noire réticulée par la stimulation électrique du noyau sous-thalamique." Grenoble 1, 2009. https://tel.archives-ouvertes.fr/tel-00414218.
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La stimulation haute fréquence (SHF) du noyau sous-thalamique (NST) est un traitement efficace dans l'abolition des symptômes moteurs de la maladie de Parkinson. Cependant, les mécanismes cellulaires et moléculaires qui sous-tendent ces effets sont encore loin d'être élucidés. Le laboratoire avait précédemment montré que la SHF du NST entraîne une augmentation des taux extra cellulaires de glutamate et de GABA chez les animaux éveillés ou anesthésiés dans une des principales structures cibles du NST, la substance noire réticulée (SNr). Au niveau de la SNr, les données suggèrent que la régulation de l'activité des neurones nigraux est due à la mise en œuvre conjointe d'une excitation des neurones glutamatergiques du NST et une implication des fibres de passages GABAergiques provenant du GPe et passant au voisinage de la zone sous-thalamique stimulée. L'objectif de ce travail de thèse est d'étudier l'implication des cellules gliales dans les réponses cellulaires de la SNr, sous stimulation du NST, et repose sur la mise en place d'une technique d'imagerie sur tranches de cerveau de rat adultes. Les tranches horizontales de cerveau contiennent à la fois le NST et la SNr, avec un maintien des connexions glutamatergiques subthalamonigrales. Dans un premier temps, nous avons montré par immunohistochimie que la SNr contient 32% de neurones pour 68% de cellules gliales. Par la suite, nous avons montré que la SHF du NST induit une réponse calcique dans environ 12% des cellules gliales de la SNr. Ces réponses calciques enregistrées dans les cellules gliales impliquent à la fois du glutamate, du GABA et de l'ATP libérés dans la SNr lors de la SHF du NST. Cette étude a donc permis de montrer que les transmetteurs libérés dans la SNr sous l'effet de la SHF du NST, comme le glutamate et le GABA, peuvent activer les cellules gliales de cette structure. Elle a également permis de mettre en évidence la libération au sein de la SNr, d'un des principaux gliotransmetteurs, l'ATP. Ainsi, les cellules gliales de la SNr répondent à la SHF du NST, et il est probable qu'elles soient impliquées dans la modulation de l'activité neuronale de cette structureHigh-frequency stimulation of the subthalamic nucleus (STN-HFS) is an effective treatment for alleviating the motor symptoms of parkinsonian patients. However, the cellular and molecular mechanisms of its effects remain under debate. Marc Savasta's laboratory had previously shown that, in awake or anaesthetized rats, STN-HFS increased extracellular glutamate and GABA contents in one of the main output nuclei of the STN, substantia nigra pars reticulata (SNr). Within the SNr, data suggested that, under NST stimulation, the regulation of neuronal activity is conjointly due to the excitation of NST glutamatergic neurons and the involvement of GABAergic fibers coming from the GPe and passing near the stimulated area. The aim of the present study is to study glial cell implication in the cellular response to STN-HFS within the SNr, by using a calcium imaging technique in adult rat brain slices. Rat brain horizontal slices, containing both STN and SNr, and respecting at best their glutamatergic connections, were used. We show by immunochemistry that the SNr contains 32% of neuron versus 68% of glial cells. Then, we show that STN-HFS induced a calcium response in almost 12% of SNr glial cells population. These calcium responses involved the release of glutamate, GABA and ATP within the SNr. Thus, this study shows that glutamate and GABA, known to be released within SNr under STN-HFS, are able to activate glial cells. Moreover, it provides evidence that ATP, one of the main gliotransmitter, is released within the SNr under STN-HFS. Thus, SNr glial cells respond to the STN-HSF and could potentially be involved in the modulation of neuronal activity in this structure
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Kanter, Marlene. "Organisationsprinzipien der extrazellulären Matrix in der Substantia nigra des Menschen und ihr Bezug zum Morbus Parkinson." Doctoral thesis, Universitätsbibliothek Leipzig, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-62572.
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Der Morbus Parkinson ist durch den selektiven Zelltod der dopaminergen Neurone der Substantia nigra pars compacta gekennzeichnet. Hierbei sind die verschiedenen Populationen pigmentierter Neurone innerhalb der SNc unterschiedlich stark
betroffen. Die Ursachen für diese unterschiedliche Schädigung sind noch nicht bekannt. Möglicherweise besteht aber ein Zusammenhang mit der Verteilung der extrazellulären Matrix innerhalb der Substantia nigra. Für die Untersuchung wurden immunhistochemische Methoden an Hirnschnittserien von menschlichen Kontrollgehirnen angewandt. Zur Darstellung von Komponenten der extrazellulären Matrix wurden drei verschiedene Antikörper genutzt. Dazu gehörten anti- CRTL-1, welcher das Link- Protein 1 von CSPGs detektiert, ein Aggrecan- Antikörper ( Klon HAG7D4), welcher an das Kern- Protein menschlichen Aggrecans bindet, sowie anti- Proteoglykan- Di-0S (Klon 1B5), der die Reste der Chondroitin- Sulfat- Seitenketten verschiedener Proteoglykane detektiert, die nach Verdau mit Chondroitinase ABC übrigbleiben. Zur räumlichen Orientierung und strukturellen Gliederung der Substantia nigra nach der von Damier et al. ( 1999) beschriebenen Calbindin- Methode, auf deren Grundlage die SNc in eine Calbindin-reiche Matrix und Calbindin- arme Bereiche, die sogenannten Nigrosomen, gegliedert wird, wurden benachbarte Hirnschnitte mit anti- Calbindin D₂₈K behandelt. Es zeigte sich, dass extrazelluläre Matrix in Form von perineuronalen Netzen nur an den nicht pigmentierten Neuronen der SNr und SNl vorkommt, während die pigmentierten Neurone der SNc keine perineuronalen Netze besitzen, aber von einer Vielzahl von ACs kontaktiert werden. Deren Dichte war an großen, stark Melanin- haltigen Neuronen am höchsten, sodass in der dorsalen Schicht der SNc, also in den Nigrosomen 3 und 4, besonders viel extrazelluläre Matrix detektiert werden konnte. Im ventralen Anteil der SNc war entsprechend der unterschiedlichen Zellgrößen, insbesondere in Nigrosom 1, eine heterogene Verteilung der extrazellulären Matrix
festzustellen. Zur Untersuchung über mögliche Veränderungen der extrazellulären Matrix im Verlauf des Morbus Parkinson wurden Hirnschnitte menschlicher Gehirne mit diagnostiziertem Morbus Parkinson ebenfalls mit den drei Antikörpern zur Darstellung der extrazellulären Matrix behandelt. Dabei zeigte sich, dass insgesamt
die Menge extrazellulärer Matrix verringert scheint. Eine Darstellung der
perineuronalen Netze mit anti- Proteoglykan- Di-0S (Klon 1B5) war nicht mehr möglich. Wie bereits in früheren Studien verschiedener Autoren festgestellt, waren die stärksten Auswirkungen der neurodegenerativen Prozesse im ventralen Anteil der
SNc, vor allem in Nigrosom 1, auszumachen, während die Neurone der Nigrosomen 3 und 4 im dorsalen Anteil weniger vulnerabel erscheinen. Diese Ergebnisse verstärken die Annahme, dass die extrazelluläre Matrix eine protektive Funktion für bestimmte Neuronengruppen besitzt. Bei der Parkinsonschen Erkrankung wird möglicherweise zuerst dieses Schutzsystem zerstört bevor es zum progressiven
Neuronenverlust kommt. Ungeklärt bleibt weiterhin was die Ursachen dafür sind.
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Pfreundtner, Claudia. "Wirkung von Cannabinoiden auf die Neurotransmission im Corpus striatum und in der Substantia nigra pars reticulata." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972359540.
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Schaeff, Sulamith [Verfasser], Marcel [Gutachter] Romanos, and Camelia-Maria [Gutachter] Monoranu. "Correlates of Substantia Nigra Echogenicity in Healthy Children / Sulamith Schaeff ; Gutachter: Marcel Romanos, Camelia-Maria Monoranu." Würzburg : Universität Würzburg, 2021. http://d-nb.info/1229352503/34.
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Hetzer, Anna Maria [Verfasser]. "Die exofokale postischämische neuronale Degeneration der Substantia nigra nach striatalem Infarkt im Mausmodell / Anna Maria Hetzer." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1076038697/34.
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Delgado, Zabalza Lorena. "Electrophysiological characterization of neuronal diversity in the substantia nigra pars reticulata in control and parkinsonian mice." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0052.
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La substance noire réticulée (SNr) est la principale structure de sortie des ganglions de la base (BG), un réseau sous-cortical contrôlant l'élaboration des programmes moteurs ainsi que des fonctions d'apprentissage cognitives et associatives. L'identification de types de cellules distincts dans le BG a joué un rôle clé pour comprendre les propriétés et les fonctions de ce circuit. Des études récentes suggèrent que la SNr est composé de plusieurs types de cellules mais jusqu'à présent cette diversité neuronale n'a jamais été prise en compte concernant le fonctionnement normal et pathologique de ce noyau, notamment dans la maladie de Parkinson (MP). En combinant des approches immunohistochimiques et électrophysiologiques chez la lignée de souris PVCre::Ai9T, nous avons démontré que les neurones de la SNr exprimant la protéine parvalbumine (PV+) ont des propriétés anatomiques et électrophysiologiques différentes de celles des neurones ne l’exprimant pas (PV-). Notre analyse anatomique montre que les neurones PV+ et PV- sont présents à proportion égale dans la SNr, mais avec une distribution distincte, les neurones PV+ étant enrichis dans la partie latérale de la SNr alors que les neurones PV- sont présents dans la partie médiale de ce noyau. Nos enregistrements électrophysiologiques in vitro ont révélé que les neurones PV+ ont une activité électrique plus élevée que les cellules PV-. De plus, nos données indiquent que la perte de dopamine (DA) et le traitement à la L-DOPA induisent une réduction profonde de l'excitabilité des neurones PV+ de la SNr dans un modèle murin de MP (la souris 6-OHDA) sans modifier l'activité des neurones PV-.Il est bien connu que l'activité des neurones de la SNr est contrôlée par les afférences GABAergiques des neurones striataux (STR-SNr) de la voie directe (dSPN) et du globus pallidus (GP-SNr). Nous avons effectué une manipulation optogénétique de ces deux voies inhibitrices et montré que ces deux populations neuronales sont innervées de manière équivalente par le STR et le GP. Nos résultats ont également révélé que l'inhibition striatale était plus efficace que l’inhibition pallidale pour réduire l'activité des deux sous-types de neurones SNr. De plus, nous avons observé que les2synapses STR-SNr et GP-SNr affichent la même plasticité à court terme sur les neurones PV+ et PV- de la SNr. Enfin, nous avons montré que la transmission GABAergique est affectée de manière différentielle sur les cellules PV+ et PV- suite à une déplétion DAergique. D'une part, les neurones PV+ sont plus sensibles à l'inhibition striatale que les cellules PV- après une déplétion en DA. D’autre part, l’inhibition pallidale est réduite sur les neurones PV+ et augmentée sur les PV- après la perte de DA, suggérant un déséquilibre de l'inhibition pallidale entre ces deux populations SNr.Il est aussi connu que les niveaux extracellulaires de GABA sont élevés dans la SNr chez les modèles rongeurs de MP, ce qui suggère que les neurones de la SNr pourraient être inhibés de manière permanente par une inhibition dite tonique. Ainsi, Nous avons caractérisé la transmission extrasynaptique GABAergique dans la SNr des souris témoins et 6-OHDA. Nos enregistrements de patch-clamp ont révélés que les neurones PV- présentent une inhibition tonique plus importante que les cellules PV+ chez les souris témoins. La présence et l'implication des sous-unités δ et α5 dans les récepteurs GABAA extrasynaptiques ont également été étudiées, révélant une présence et un effet majeurs des sous-unités α5 sur les neurones PV. Cependant, contrairement à ce qui était attendu, la déplétion chronique en DA ne provoque aucun changement de l'inhibition tonique ni dans les cellules PV+ ni dans les neurones PV- de la SNr.Nos résultats mettent en évidence l'importance de différencier les populations cellulaires de la SNr pour une meilleure connaissance du fonctionnement des BG en situation physiologique et physiopathologique tel que dans la MPThe substantia nigra pars reticulate (SNr) is the main output structure of the basal ganglia (BG), a subcortical network controlling the elaboration of motor programs as well as cognitive and associative learning functions. The identification of distinct cell-types within the BG has played a key role for understanding the properties and functions of this circuit. Recent studies suggest that the SNr is composed of several cell types but until now this neuronal diversity has never been taken into consideration regarding normal and pathological functioning of this nucleus, particularly in Parkinson’s disease (PD). By combining immunohistochemical and electrophysiological approaches in the PVCre::Ai9T mouse line, we have demonstrated that SNr neurons expressing the protein parvalbumin (PV+) exhibit different anatomical and electrophysiological properties than non PV-expressing (PV-) neurons. Our anatomical analysis reveal that PV+ and PV- neurons are present in equal proportion in the SNr, but with a distinct distribution, PV+ being enriched in the lateral part of the SNr, while PV- are found in the medial portion of the nucleus. In vitro electrophysiological recordings from identified PV+ and PV- neurons in the SNr also revealed that PV+ neurons fired at relatively higher rates than PV- cells. Additionally, our data revealed that DA loss and subsequent L-DOPA treatment induce a profound reduction of the excitability of PV+ SNr neurons in a 6-OHDA mouse model of PD while activity of PV- remains unchanged by these treatments.It is well known that the activity of SNr neurons is controlled by GABAergic inputs from striatal dSPN and the GP. We performed optogenetic manipulation of STR-SNr and GP-SNr inputs in order to determine whether PV+ and PV- SNr neurons received equivalent inputs from these two nuclei. We tested the impact of STR-SNr or GP-SNr activation on the activity of SNr neurons in cell-attached configuration and then switched to whole-cell voltage-clamp to characterize short-term plasticity of these synapses. Our results show that both PV+ and PV- SNr neurons are innervated by the STR and the GP. They also revealed that inhibition from dSPN was more powerful to silence activity of both subtypes of SNr neurons. Indeed, we observed that both STR-SNr and GP-SNr synapses displayed short-term depression in PV+ and PV- SNr neurons. DA loss affected GABA transmission in a different manner in PV+ and PV- SNr cells. On one hand, PV+ neurons were more sensible to striatal synaptic inhibition than PV- cells after DA depletion. On the other hand, PV-GP inputs were reduced on PV+ neurons and increased in PV- cells after DA loss suggesting a disequilibrium in pallidal inhibition between these two SNr populations.Furthermore, considering that rodent models of PD have shown elevated extracellular levels of GABA in the SNr which can exert a tonic extrasynaptic inhibition on SNr neurons, we decided to characterize GABAergic extrasynaptic transmission in the SNr of control and 6-OHDA lesioned mice. We studied GABAA mediated tonic inhibition by performing whole-cell patch-clamp recordings of PV+ and PV- SNr neurons in acute slices. We observed that PV- SNr neurons displayed larger GABAA receptor-mediated tonic currents than PV+ cells in the SNr of control mice. The presence and involvement of δ and/or α5 extrasynaptic subunits in GABAA receptors mediating this type of transmission was also studied, revealing a major presence and effect of α5-subunits on PV- neurons probably mediating the tonic currents observed in these neurons. However, contrary to expected, chronic DA-depletion did not trigger any increase in tonic inhibition neither in PV+ cells nor in PV- SNr neurons.All these findings highlight the importance of differentiating cell populations in the SNr to a better knowledge of the BG circuit in normal and pathological states such as in PD
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Heiland, Bettina. "Die nicht-cholinerge Funktion der Azetylcholinesterase in dopaminergen Gebieten des ZNS in gesunden, pathologischen und sich entwickelnden Systemen The non-cholinergic function of acetylcholinesterase in the dopaminergic areas of the CNS in healthy, pathological and developing systems /." [S.l.] : [s.n.], 2002. http://elib.tu-darmstadt.de/diss/000319.
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Chen, Yan. "EFFECTS OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR (GDNF) ON STEM/PROGENITOR CELL PROLIFERATION AND DIFFERENTIATION." UKnowledge, 2005. http://uknowledge.uky.edu/gradschool_diss/233.
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Stem/progenitor cells are present in the adult brain; they undergo constantproliferation and differentiate into mature neurons in certain brain areas, a phenomenoncalled neurogenesis. This study investigated the effects of GDNF, a potent trophic factorof dopaminergic neurons, on neurogenesis in the brain. Nestin and 5-Bromo-2'-deoxyuridine (BrdU) were used as stem/progenitor cells markers.First, we observed extensive bilateral increases of stem/progenitor cells in thedentate gyrus and substantia nigra after continuous infusion of GDNF into the normal ratbrain. However, none of the BrdU+ cells showed neuronal features in the substantia nigraas characterized by immunocytochemical procedures. Next, we identified themorphology of BrdU+ cells after infusing the marker into the brain. While the proceduresincreased the BrdU labeling, neurogenesis was not observed in the basal ganglia. Underelectron microscope, the BrdU+ cells either were undifferentiated or showedcharacteristics of astrocytes. This observation is consistent with suggestions thatastrocytes serve as multipotent progenitors. Later, we repeated GDNF intrastriatalinfusion one month after a severe 6-hydroxydopamine (6-OHDA) lesion. The number ofBrdU+ cells was significantly higher in the GDNF recipients in the ipsilateral substantianigra and both sides of the dentate gyrus. However, no neurogenesis was observed. Inaddition, motor functions were not improved by GDNF treatment. Thus, we measured theeffects of GDNF administration directly into the substantia nigra six hours before apartial 6-OHDA lesion. HPLC measurements of dopamine and its metabolites showed asignificant increase of tissue level in the substantia nigra and striatum, respectively.Despite this, no newly generated dopaminergic neurons was detected in the basal ganglia.Taken together, our studies investigated the effects of GDNF on adultstem/progenitor cells in normal and lesioned rat brain. For the first time, we demonstratedthat GDNF promoted their proliferation in the dentate gyrus, suggesting it has a role inneurogenesis and the function of learning and memory. In each scenario, GDNFpromoted stem/progenitor cell proliferation, but failed to induce neurogenesis in thesubstantia nigra. We believed that the local microenvironment in the substantia nigra mayprevent the stem/progenitor cells to mature into functional neurons.
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Akaoka, Hidéo. "Régulation dopaminergique de l'activité électrique des neurones du système nigro-strié." Lyon 1, 1990. http://www.theses.fr/1990LYO1T008.
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Rheey, Jinguen. "Otx2 promotes survival of injured adult retinal ganglion cells non cell-autonomously and regulates development of inner retinal cells in post-natal mouse cell autonomously." Paris 6, 2011. http://www.theses.fr/2011PA066176.
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Dickerson, Jonathan W. "Neuroprotective and neurorestorative effects of neuregulins in the injured and aged dopaminergic nigrostriatal system." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288981932.
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Bacon, Gregory. "The anatomical basis for 5-HT-dopamine interactions in the rat substantia nigra and ventral tegmental area." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249483.
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Whyte, Kathryn Antonia. "Investigation of non-cholinergic acetylcholinesterase, and related peptides in an in vitro preparation of the substantia nigra." Thesis, University of Oxford, 2001. http://ora.ox.ac.uk/objects/uuid:967be89b-1b57-4d56-98de-70b4376ba1b3.
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The primary role of acetylcholinesterase (AChE) is hydrolysis of acetylcholine (ACh). However, observations by numerous groups have suggested that AChE may have non-cholinergic functions. Furthermore, developmental roles for AChE and its related enzyme, butyrylcholinesterase (BuChE), which is also capable of ACh hydrolysis, have been postulated. One line of evidence to support a non-cholinergic role for AChE is the apparent disparity in several brain areas between the distribution of AChE and the cholinergic marker choline acetyltransferase. The substantia nigra (SN), an area of the ventral mesencephalon (VM), which contains the dopaminergic cells that degenerate in Parkinson's disease (PD), is an area that displays such a disparity. One approach to treating PD involves implantation of embryonic dopaminergic VM cells into the parkinsonian brain. This procedure, known as foetal transplantation, has met with limited success, in part due to degeneration of dopaminergic cells within the donor preparation. It is known that incorporation of trophic factors into the preparation for grafting improves dopaminergic cell survival. It has previously been shown that AChE enhances survival and neurite outgrowth of postnatal dopaminergic cells in organotypic cultures of the VM. The aim of the studies in this thesis was to establish the effects of BuChE and AChE on embryonic dopaminergic neurons in a preparation analogous to that used in the animal model of foetal transplantation as a treatment for PD. Addition of BuChE and monomeric (G1-) and tetrameric (G4-) forms of AChE enhanced dopaminergic neurite outgrowth. Inhibition of the active site of BuChE and AChE by echothiophate had no effect upon neurite outgrowth or cell survival, demonstrating that the trophic effects of BuChE and AChE on neurite outgrowth were not dependent upon ACh hydrolysis. In contrast, inhibition of the peripheral anionic site (PAS) of AChE by BW284c51 markedly decreased cell survival and neurite outgrowth. The mechanism of action of BW284c51 toxicity was subsequently investigated using a mixture of nicotinic ACh receptor antagonists in order to demonstrate that the chronic toxic effects of BW284c51 were not a consequence of elevated ACh resulting from inhibition of AChE. Finally, the technique of whole-cell patch-clamp electrophysiology revealed a novel inhibitory effect of BuChE and G1- and G4-AChE on voltage-dependent calcium currents. It was postulated that these actions underlie the trophic effects of BuChE and AChE on embryonic dopaminergic neurons, a suggestion that was supported by the findings that established inhibitors of voltage-dependent calcium currents enhanced dopaminergic neurite outgrowth. The findings of this thesis are discussed in the context of other studies and are related to both physiological and pathological functions of the central nervous system.
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Braitmaier, Helmine [Verfasser]. "Genetische Analyse der Echogenität der Substantia nigra und des gestörten Eisenstoffwechsels bei der Parkinsonschen Krankheit / Helmine Braitmaier." München : Verlag Dr. Hut, 2011. http://d-nb.info/1012432343/34.
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