GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABA A receptors.

Autor: Patel JC; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address: jyotiben.patel@nyulangone.org., Sherpa AD; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; Center for Neural Science New York University, 4 Washington Place, New York, NY 10003, USA., Melani R; NYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA., Witkovsky P; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA., Wiseman MR; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA., O'Neill B; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA., Aoki C; NYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; Center for Neural Science New York University, 4 Washington Place, New York, NY 10003, USA., Tritsch NX; NYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA., Rice ME; Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA. Electronic address: margaret.rice@nyu.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2024 Mar 26; Vol. 43 (3), pp. 113834. Date of Electronic Publication: 2024 Mar 02.
DOI: 10.1016/j.celrep.2024.113834
Abstrakt: Striatal dopamine axons co-release dopamine and gamma-aminobutyric acid (GABA), using GABA provided by uptake via GABA transporter-1 (GAT1). Functions of GABA co-release are poorly understood. We asked whether co-released GABA autoinhibits dopamine release via axonal GABA type A receptors (GABA A Rs), complementing established inhibition by dopamine acting at axonal D2 autoreceptors. We show that dopamine axons express α3-GABA A R subunits in mouse striatum. Enhanced dopamine release evoked by single-pulse optical stimulation in striatal slices with GABA A R antagonism confirms that an endogenous GABA tone limits dopamine release. Strikingly, an additional inhibitory component is seen when multiple pulses are used to mimic phasic axonal activity, revealing the role of GABA A R-mediated autoinhibition of dopamine release. This autoregulation is lost in conditional GAT1-knockout mice lacking GABA co-release. Given the faster kinetics of ionotropic GABA A Rs than G-protein-coupled D2 autoreceptors, our data reveal a mechanism whereby co-released GABA acts as a first responder to dampen phasic-to-tonic dopamine signaling.
Competing Interests: Declaration of interests B.O. is currently employed at Addgene but was not when contributing to this study.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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