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Local gamma-aminobutyric acid and glutamate circuit control of hypophyseotrophic corticotropin-releasing factor neuron activity in the paraventricular nucleus of the hypothalamus

Bartanusz, V.
Gaillard, R. C.
Streit, P.
Published in European Journal of Neuroscience. 2004, vol. 19, no. 3, p. 777-782
Abstract Paraventricular corticotropin-releasing factor (CRF) neurons play a pivotal role in regulating neuroendocrine responses to stress. The mechanisms by which synaptic inputs control the activity of these neurons are not well understood. The present study was undertaken to determine the role of the intrinsic gamma-aminobutyric acid (GABA)- and glutamatergic neural circuits of the hypothalamic paraventricular nucleus (PVN) in the control of CRF neural activity. We show that in organotypic cultures of the PVN, blockade of the intrinsic GABAergic neurotransmission by the GABAA receptor antagonist bicuculline resulted in a significant increase in CRF secretion. The bicuculline-induced CRF secretory activity was abolished by the coadministration of the selective alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Electrical stimulation of the CRF cell division elicited glutamatergic extracellular field potentials that were dramatically enhanced by bicuculline and were suppressed by CNQX. These results show that the functional activity of CRF neurons in organotypic cultures of the PVN is under a tonic inhibitory influence of an intrinsic GABAergic circuit. Suppression of GABAergic transmission appears to have a permissive role for inducing an increased secretory activity of CRF neurons that is driven by an excitatory glutamatergic network via AMPA/kainate receptors.
Keywords AnimalsBicuculline/pharmacologyCorticotropin-Releasing Hormone/ metabolismDrug InteractionsElectric StimulationEvoked Potentials/drug effectsExcitatory Amino Acid Agonists/pharmacologyExcitatory Amino Acid Antagonists/pharmacologyGABA Antagonists/pharmacologyGlutamic Acid/metabolism/ physiologyImmunohistochemistry/methodsMicroscopy, Electron/methodsNeurons/drug effects/metabolism/ physiology/ultrastructureOrgan Culture TechniquesParaventricular Hypothalamic Nucleus/ cytology/drug effectsRadiometry/methodsRatsRats, Sprague-DawleySynapses/drug effects/metabolism/ultrastructureValine/ analogs & derivatives/pharmacologyGamma-Aminobutyric Acid/metabolism/ physiology
Stable URL http://archive-ouverte.unige.ch/unige:10176
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PMID: 14984429
Research group Progéniteurs neuronaux

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Deposited on : 2010-08-06

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