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

Autor: Joseph J. Lebowitz, Aditi Banerjee, Claire Qiao, James R. Bunzow, John T. Williams, Pascal S. Kaeser
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 1, Pp 111915- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.111915
Popis: Summary: 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.
Databáze: Directory of Open Access Journals