| First Author | Lebowitz JJ | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 1 | Pages | 111915 |
| PubMed ID | 36640316 | Mgi Jnum | J:333425 |
| Mgi Id | MGI:7434091 | Doi | 10.1016/j.celrep.2022.111915 |
| Citation | Lebowitz JJ, et al. (2023) Synaptotagmin-1 is a Ca(2+) sensor for somatodendritic dopamine release. Cell Rep 42(1):111915 |
| abstractText | 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(2+) sensors. We here use mouse genetics and whole-cell electrophysiology to establish that the fast Ca(2+) 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(2+) sensor Syt-1, leading to synchronous release in response to the initial stimulus. |
