eLife (Sep 2019)

RIM is essential for stimulated but not spontaneous somatodendritic dopamine release in the midbrain

  • Brooks G Robinson,
  • Xintong Cai,
  • Jiexin Wang,
  • James R Bunzow,
  • John T Williams,
  • Pascal S Kaeser

DOI
https://doi.org/10.7554/eLife.47972
Journal volume & issue
Vol. 8

Abstract

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Action potentials trigger neurotransmitter release at active zones, specialized release sites in axons. Many neurons also secrete neurotransmitters or neuromodulators from their somata and dendrites. However, it is unclear whether somatodendritic release employs specialized sites for release, and the molecular machinery for somatodendritic release is not understood. Here, we identify an essential role for the active zone protein RIM in stimulated somatodendritic dopamine release in the midbrain. In mice in which RIMs are selectively removed from dopamine neurons, action potentials failed to evoke significant somatodendritic release detected via D2 receptor-mediated currents. Compellingly, spontaneous dopamine release was normal upon RIM knockout. Dopamine neuron morphology, excitability, and dopamine release evoked by amphetamine, which reverses dopamine transporters, were also unaffected. We conclude that somatodendritic release employs molecular scaffolds to establish secretory sites for rapid dopamine signaling during firing. In contrast, basal release that is independent of action potential firing does not require RIM.

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