A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo
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- Mahalakshmi Somayaji
- Department of Psychiatry, Columbia University, New York, NY 10032;
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- Stefano Cataldi
- Department of Psychiatry, Columbia University, New York, NY 10032;
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- Se Joon Choi
- Department of Psychiatry, Columbia University, New York, NY 10032;
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- Robert H. Edwards
- Department of Physiology, University of California, San Francisco, CA 94518;
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- Eugene V. Mosharov
- Department of Psychiatry, Columbia University, New York, NY 10032;
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- David Sulzer
- Department of Psychiatry, Columbia University, New York, NY 10032;
抄録
<jats:title>Significance</jats:title> <jats:p>We report a long-sought& in vivo& physiological role for& α-synuclein (α-syn) in dopamine signaling. The results indicate that& α-syn is critical for activity-dependent dopamine plasticity, and that short repeated burst activity produces rapid presynaptic facilitation, while prolonged burst activity slowly depresses evoked dopamine release. We propose that the rapid facilitation is due to an enhanced fusion of synaptic vesicles at active zones during exocytosis while the depression is due to synaptic exhaustion. These results identify a& dynamic role of& α-syn, and are critical for defining& molecular mechanisms and therapeutic targets for various neurological disorders, where the firing properties of neurons are severely altered.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 117 (51), 32701-32710, 2020-12-03
Proceedings of the National Academy of Sciences