Synaptotagmin-1 is a Ca2+ sensor for somatodendritic dopamine release

Joseph J. Lebowitz, Aditi Banerjee, Claire Qiao, James R. Bunzow, John T. Williams, Pascal S. Kaeser

Research output: Contribution to journalArticlepeer-review

Abstract

Modes of somatodendritic transmission range from rapid synaptic signaling to protracted regulation over distance. Somatodendritic dopamine secretion in the midbrain leads to D2 receptor-induced modulation of dopamine neurons on the timescale of seconds. Temporally imprecise release mechanisms are often presumed to be at play, and previous work indeed suggested roles for slow Ca2+ sensors. We here use mouse genetics and whole-cell electrophysiology to establish that the fast Ca2+ sensor synaptotagmin-1 (Syt-1) is important for somatodendritic dopamine release. Syt-1 ablation from dopamine neurons strongly reduces stimulus-evoked D2 receptor-mediated inhibitory postsynaptic currents (D2-IPSCs) in the midbrain. D2-IPSCs evoked by paired stimuli exhibit less depression, and high-frequency trains restore dopamine release. Spontaneous somatodendritic dopamine secretion is independent of Syt-1, supporting that its exocytotic mechanisms differ from evoked release. We conclude that somatodendritic dopamine transmission relies on the fast Ca2+ sensor Syt-1, leading to synchronous release in response to the initial stimulus.

Original languageEnglish (US)
Article number111915
JournalCell Reports
Volume42
Issue number1
DOIs
StatePublished - Jan 31 2023

Keywords

  • calcium sensor
  • CP: Neuroscience
  • dopamine
  • exocytosis
  • neurotransmission
  • secretion
  • somatodendritic release
  • synaptotagmin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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