GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors
Summary: 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 (...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724001621 |
| _version_ | 1797281221641764864 |
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| author | Jyoti C. Patel Ang D. Sherpa Riccardo Melani Paul Witkovsky Madeline R. Wiseman Brian O’Neill Chiye Aoki Nicolas X. Tritsch Margaret E. Rice |
| author_facet | Jyoti C. Patel Ang D. Sherpa Riccardo Melani Paul Witkovsky Madeline R. Wiseman Brian O’Neill Chiye Aoki Nicolas X. Tritsch Margaret E. Rice |
| author_sort | Jyoti C. Patel |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-07T16:54:16Z |
| format | Article |
| id | doaj.art-e48159068c3b46c2932e5c1bf48dad25 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-07T16:54:16Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-e48159068c3b46c2932e5c1bf48dad252024-03-03T04:29:41ZengElsevierCell Reports2211-12472024-03-01433113834GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptorsJyoti C. Patel0Ang D. Sherpa1Riccardo Melani2Paul Witkovsky3Madeline R. Wiseman4Brian O’Neill5Chiye Aoki6Nicolas X. Tritsch7Margaret E. Rice8Department of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USA; Corresponding authorDepartment 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, USANYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USADepartment of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USADepartment of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USADepartment of Neurosurgery, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USANYU 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, USANYU Neuroscience Institute, New York University Grossman School of Medicine, 550 First Avenue, New York, NY 10016, USADepartment 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124724001621CP: Neuroscience |
| spellingShingle | Jyoti C. Patel Ang D. Sherpa Riccardo Melani Paul Witkovsky Madeline R. Wiseman Brian O’Neill Chiye Aoki Nicolas X. Tritsch Margaret E. Rice GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors Cell Reports CP: Neuroscience |
| title | GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors |
| title_full | GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors |
| title_fullStr | GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors |
| title_full_unstemmed | GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors |
| title_short | GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors |
| title_sort | gaba co released from striatal dopamine axons dampens phasic dopamine release through autoregulatory gabaa receptors |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724001621 |
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