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 language | English (US) |
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Article number | 111915 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 1 |
DOIs | |
State | Published - Jan 31 2023 |
Keywords
- CP: Neuroscience
- calcium sensor
- dopamine
- exocytosis
- neurotransmission
- secretion
- somatodendritic release
- synaptotagmin
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology