Synaptotagmin-1 is a Ca Sensor for Somatodendritic Dopamine Release

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2023 Jan 14

PMID 36640316

Authors

Joseph J Lebowitz

Aditi Banerjee

Claire Qiao

James R Bunzow

John T Williams

Pascal S Kaeser

Affiliations

Soon will be listed here.

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 Ca sensors. We here use mouse genetics and whole-cell electrophysiology to establish that the fast Ca 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 Ca sensor Syt-1, leading to synchronous release in response to the initial stimulus.

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