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

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.

SUBMITTER: Lebowitz JJ 

PROVIDER: S-EPMC9993464 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature