dc.contributor.author | Chazalon, Marine | |
dc.contributor.author | Paredes Rodríguez, Elena | |
dc.contributor.author | Morin, Stéphanie | |
dc.contributor.author | Martinez, Audrey | |
dc.contributor.author | Cristóvão-Ferreira, Sofia | |
dc.contributor.author | Vaz, Sandra | |
dc.contributor.author | Sebastiao, Ana | |
dc.contributor.author | Panatier, Aude | |
dc.contributor.author | Boué-Grabot, Eric | |
dc.contributor.author | Miguélez Palomo, Cristina | |
dc.contributor.author | Baufreton, Jérôme | |
dc.date.accessioned | 2018-11-27T11:59:29Z | |
dc.date.available | 2018-11-27T11:59:29Z | |
dc.date.issued | 2018-05-08 | |
dc.identifier.citation | Cell Reports 23(6) : 1678-1690 (2018) | es_ES |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/10810/29869 | |
dc.description.abstract | The external globus pallidus (GP) is a key GABAergic hub in the basal ganglia (BG) circuitry, a neuronal network involved in motor control. In Parkinson's disease (PD), the rate and pattern of activity of GP neurons are profoundly altered and contribute to the motor symptoms of the disease. In rodent models of PD, the striato-pallidal pathway is hyperactive, and extracellular GABA concentrations are abnormally elevated in the GP, supporting the hypothesis of an alteration of neuronal and/or glial clearance of GABA. Here, we discovered the existence of persistent GABAergic tonic inhibition in GP neurons of dopamine-depleted (DD) rodent models. We showed that glial GAT-3 transporters are down-regulated while neuronal GAT-1 function remains normal in DD rodents. Finally, we showed that blocking GAT-3 activity in vivo alters the motor coordination of control rodents, suggesting that GABAergic tonic inhibition in the GP contributes to the pathophysiology of PD. | es_ES |
dc.description.sponsorship | This work was supported by the French Agence Nationale de la Recherche (grants 08-JCJC-0087 and 2015-CE37-0006), the Euroregion Aquitaine-Euskadi (Neurosciences grant number 9), the Basque Government (C.M. postdoctoral grant), the LABEX BRAIN ANR-10-LABX-43 grant (M.C. post-doctoral grant), a grant from Fundacao para a Ciencia e Tecnologia (SFRH/BPD/81627/2011, S.V. post-doctoral grant), and H2020 Twinning action SynaNet (grant agreement 692340). We are grateful to S.H. Oliet, E. Audinat, and D. Voisin for insightful scientific discussions; UPV/EHU SGIker for their collaboration; and the Bordeaux Imaging Center of the University of Bordeaux. We also want to thank Dr. Vincenzo Crunelli for generously providing the 5 subunit knockout mice. We are also grateful to Dr. Patricia Gongal for language assistance on the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/692340 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | extrasynaptic gaba(a) receptors | es_ES |
dc.subject | monkey basal ganglia | es_ES |
dc.subject | synaptic-transmission | es_ES |
dc.subject | subthalamic nucleus | es_ES |
dc.subject | projection neurons | es_ES |
dc.subject | transporter gat-1 | es_ES |
dc.subject | beta oscillations | es_ES |
dc.subject | adult-rat | es_ES |
dc.subject | in-vitro | es_ES |
dc.subject | plasticity | es_ES |
dc.title | GAT-3 Dysfunction Generates Tonic Inhibition in Exter nal Globus Pallidus Neurons in Parkinsonian Rodents | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | 2018 The Author(s).This is an open access article under the terms of the Creative Commos Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/). | es_ES |
dc.rights.holder | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2211124718305436?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.celrep.2018.04.014 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |