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Updated: Sep 28, 2025

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Synaptotagmins 1 and 7 Play Complementary Roles in Somatodendritic Dopamine Release.

Takuya Hikima1, Paul Witkovsky1, Latika Khatri2

  • 1Department of Neurosurgery, New York University Grossman School of Medicine, New York, New York 10016.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|April 1, 2022
PubMed
Summary

Synaptotagmin 7 (Syt7) drives somatodendritic dopamine release and its calcium sensitivity. Synaptotagmin 1 (Syt1) contributes to tonic release, with both proteins playing complementary roles in dopamine neuron function.

Keywords:
D2 dopamine receptorsGIRK channelsautoreceptorsexocytosissubstantia nigrasynaptotagmin 1

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Neurochemistry

Background:

  • The molecular basis of somatodendritic dopamine (DA) release is not fully understood.
  • Previous research indicated DA release in low extracellular calcium ([Ca2+]o).
  • Synaptotagmin proteins are calcium sensors involved in neurotransmitter release.

Purpose of the Study:

  • To investigate the role of synaptotagmin 7 (Syt7) in somatodendritic DA release.
  • To determine the calcium (Ca2+) dependence of DA release mediated by Syt7.
  • To explore the interplay between Syt7 and Syt1 in DA release.

Main Methods:

  • Whole-cell recording in midbrain slices from mice.
  • Measurement of DA-dependent D2 receptor-mediated inhibitory currents (D2ICs).
  • Application of antibodies against Syt7 and Syt1.
  • Assessment of DA release under varying extracellular Ca2+ concentrations.

Main Results:

  • Antibody to Syt7 reduced evoked D2ICs, confirming Syt7's role in DA release.
  • Syt7 mediates DA release in submillimolar [Ca2+]o; this sensitivity was lost in Syt7 knockout mice.
  • Syt1 substituted for Syt7 in phasic release in Syt7 knockouts and mediated tonic release in wild-type mice.

Conclusions:

  • Syt7 is a key high-affinity Ca2+ sensor for phasic somatodendritic DA release.
  • Syt1 contributes to tonic somatodendritic DA release and can compensate for Syt7.
  • Syt7 and Syt1 have distinct yet complementary roles in regulating DA release from midbrain neurons.