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

Overview

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.

publication date

  • November 15, 2019

Research

keywords

  • Cocaine
  • Cocaine-Related Disorders
  • Dopaminergic Neurons
  • Mesencephalon
  • alpha-Synuclein

Identity

PubMed Central ID

  • PMC6858354

Scopus Document Identifier

  • 85075181549

Digital Object Identifier (DOI)

  • 10.1002/syn.20345

PubMed ID

  • 31754648

Additional Document Info

volume

  • 2