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Alpha-synuclein is strategically positioned for afferent modulation of midbrain dopamine neurons and is essential for cocaine preference.

TitleAlpha-synuclein is strategically positioned for afferent modulation of midbrain dopamine neurons and is essential for cocaine preference.
Publication TypeJournal Article
Year of Publication2019
AuthorsTrubetckaia O, Lane AE, Qian L, Zhou P, Lane DA
JournalCommun Biol
Volume2
Pagination418
Date Published2019
ISSN2399-3642
Abstract

Alpha-synuclein (α-syn) is an abundant neuroprotein elevated in cocaine addicts, linked to drug craving, and recruited to axon terminals undergoing glutamatergic plasticity - a proposed mechanism for substance abuse. However, little is known about normal α-syn function or how it contributes to substance abuse. We show that α-syn is critical for preference of hedonic stimuli and the cognitive flexibility needed to change behavioral strategies, functions that are altered with substance abuse. Electron microscopic analysis reveals changes in α-syn targeting of ventral tegmental area axon terminals that is dependent upon the duration of cocaine exposure. The dynamic changes in presynaptic α-syn position it to control neurotransmission and fine-tune the complex afferent inputs to dopamine neurons, potentially altering functional dopamine output. Cocaine also increases postsynaptic α-syn where it is needed for normal ALIX function, multivesicular body formation, and cocaine-induced exosome release indicating potentially similar α-syn actions for vesicle release pre- and post-synaptically.

DOI10.1038/s42003-019-0651-8
Alternate JournalCommun Biol
PubMed ID31754648
PubMed Central IDPMC6858354
Grant ListR01 NS067078 / NS / NINDS NIH HHS / United States