GAT-3 Dysfunction Generates Tonic Inhibition in External Globus Pallidus Neurons in Parkinsonian Rodents

Marine Chazalon, Elena Paredes-Rodriguez, Stéphanie Morin, Audrey Martinez, Sofia Cristóvão-Ferreira, Sandra Vaz, Ana Sebastiao, Aude Panatier, Eric Boué-Grabot, Cristina Miguelez, Jérôme Baufreton
Cell Reports. 2018-05-01; 23(6): 1678-1690
DOI: 10.1016/j.celrep.2018.04.014

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1. Cell Rep. 2018 May 8;23(6):1678-1690. doi: 10.1016/j.celrep.2018.04.014.

GAT-3 Dysfunction Generates Tonic Inhibition in External Globus Pallidus Neurons
in Parkinsonian Rodents.

Chazalon M(1), Paredes-Rodriguez E(2), Morin S(1), Martinez A(1), Cristóvão-Ferreira S(3), Vaz S(3), Sebastiao A(3), Panatier A(4), Boué-Grabot E(1), Miguelez C(2), Baufreton J(5).

Author information:
(1)Université de Bordeaux, Institut des Maladies Neurodégénératives, 33000
Bordeaux, France; CNRS UMR 5293, Institut des Maladies Neurodégénératives, 33000
Bordeaux, France.
(2)Department of Pharmacology, University of the Basque Country (UPV/EHU), 48940
Leioa, Spain.
(3)Institute of Pharmacology and Neurosciences, Faculty of Medicine, and Unit of
Neuroscience, Institute of Molecular Medicine, University of Lisbon, Lisbon,
Portugal.
(4)INSERM U1215, Neurocentre Magendie, 33000 Bordeaux, France; Université de
Bordeaux, 33000 Bordeaux, France.
(5)Université de Bordeaux, Institut des Maladies Neurodégénératives, 33000
Bordeaux, France; CNRS UMR 5293, Institut des Maladies Neurodégénératives, 33000
Bordeaux, France. Electronic address: .

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
downregulated 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.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.celrep.2018.04.014
PMID: 29742425


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