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

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 neuro

SUBMITTER: Trubetckaia O 

PROVIDER: S-EPMC6858354 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature