Phasic and Tonic mGlu7 Receptor Activity Modulates the Thalamocortical Network
| Autor: | Francine Acher, Julie Perroy, Delphine Rigault, Benoit Girard, Valériane Tassin, Pierre Fontanaud, Laurent Fagni, Apolline Chotte, Mikhail Kalinichev, Federica Bertaso |
|---|---|
| Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), roussel, pascale, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Metabotropic Glutamate/genetics/*metabolism [SDV]Life Sciences [q-bio] Receptors Metabotropic Glutamate Transgenic Membrane Potentials Mice Excitatory Amino Acid Agents/pharmacology 0302 clinical medicine Thalamus Neural Pathways Receptors Eeg Neural Pathways/*physiology Receptor GABA-A/physiology ComputingMilieux_MISCELLANEOUS Original Research Cerebral Cortex Neurons Benzoxazoles Post-Synaptic Density/drug effects/genetics Glutamate receptor Synaptic Potentials/drug effects/genetics Synaptic Potentials GTP-Binding Protein alpha Subunits Sensory Systems [SDV] Life Sciences [q-bio] Gq-G11/genetics/metabolism GABAergic short-term plasticity EEG Allosteric modulator GABA Agents/pharmacology Mutation/genetics GABA Agents Cognitive Neuroscience Rhodopsin/genetics/metabolism Membrane Potentials/drug effects/genetics Neuroscience (miscellaneous) Mice Transgenic glutamate In Vitro Techniques Neurotransmission Biology lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic Channelrhodopsins thalamic network Humans Animals Excitatory Amino Acid Agents Neurons/drug effects/physiology lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Excitatory Postsynaptic Potentials/drug effects/genetics Excitatory Postsynaptic Potentials Post-Synaptic Density Thalamus/*physiology Receptors GABA-A HEK293 Cells 030104 developmental biology Metabotropic glutamate receptor Mutation Benzoxazoles/chemistry/pharmacology GTP-Binding Protein alpha Subunits Gq-G11 epilepsy Cerebral Cortex/*cytology/physiology Neuroscience Postsynaptic density 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Neural Circuits Frontiers in Neural Circuits, 2016, 10, pp.31. ⟨10.3389/fncir.2016.00031⟩ Frontiers in Neural Circuits, Frontiers, 2016, 10, pp.31. ⟨10.3389/fncir.2016.00031⟩ Frontiers in Neural Circuits, Vol 10 (2016) |
| ISSN: | 1662-5110 |
| Popis: | Mutation of the metabotropic glutamate receptor type 7 (mGlu7) induces absence-like epileptic seizures, but its precise role in the somatosensory thalamocortical network remains unknown. By combining electrophysiological recordings, optogenetics, and pharmacology, we dissected the contribution of the mGlu7 receptor at mouse thalamic synapses. We found that mGlu7 is functionally expressed at both glutamatergic and GABAergic synapses, where it can inhibit neurotransmission and regulate short-term plasticity. These effects depend on the PDZ-ligand of the receptor, as they are lost in mutant mice. Interestingly, the very low affinity of mGlu7 receptors for glutamate raises the question of how it can be activated, namely at GABAergic synapses and in basal conditions. Inactivation of the receptor activity with the mGlu7 negative allosteric modulator (NAM), ADX71743, enhances thalamic synaptic transmission. In vivo administration of the NAM induces a lethargic state with spindle and/or spike-and-wave discharges accompanied by a behavioral arrest typical of absence epileptic seizures. This provides evidence for mGlu7 receptor-mediated tonic modulation of a physiological function in vivo preventing synchronous and potentially pathological oscillations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|