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GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors.
Patel, Jyoti C; Sherpa, Ang D; Melani, Riccardo; Witkovsky, Paul; Wiseman, Madeline R; O'Neill, Brian; Aoki, Chiye; Tritsch, Nicolas X; Rice, Margaret E.
Afiliación
  • 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.
Cell Rep ; 43(3): 113834, 2024 Mar 26.
Article en En | MEDLINE | ID: mdl-38431842
ABSTRACT
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 (GABAARs), complementing established inhibition by dopamine acting at axonal D2 autoreceptors. We show that dopamine axons express α3-GABAAR subunits in mouse striatum. Enhanced dopamine release evoked by single-pulse optical stimulation in striatal slices with GABAAR 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 GABAAR-mediated autoinhibition of dopamine release. This autoregulation is lost in conditional GAT1-knockout mice lacking GABA co-release. Given the faster kinetics of ionotropic GABAARs 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dopamina / Autorreceptores Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dopamina / Autorreceptores Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos