A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo

Proc Natl Acad Sci U S A. 2020 Dec 22;117(51):32701-32710. doi: 10.1073/pnas.2013652117. Epub 2020 Dec 3.

Abstract

α-Synuclein is expressed at high levels at presynaptic terminals, but defining its role in the regulation of neurotransmission under physiologically relevant conditions has proven elusive. We report that, in vivo, α-synuclein is responsible for the facilitation of dopamine release triggered by action potential bursts separated by short intervals (seconds) and a depression of release with longer intervals between bursts (minutes). These forms of presynaptic plasticity appear to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and are consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. These results indicate that the presynaptic effects of α-synuclein depend on specific patterns of neuronal activity.

Keywords: alpha-Synuclein; dopamine; in vivo neurotransmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Calcium Signaling
  • Dopamine / metabolism*
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Female
  • Isoflurane / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism*
  • Neurotransmitter Agents / metabolism
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism*
  • Synaptic Vesicles / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*
  • gamma-Synuclein / metabolism

Substances

  • Anesthetics, Inhalation
  • Neurotransmitter Agents
  • alpha-Synuclein
  • gamma-Synuclein
  • Isoflurane
  • Dopamine