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

eLife

Pascal S Kaeser¹  Xintong Cai¹  Jiexin Wang¹  Brooks G Robinson²  James R Bunzow²  John T Williams² 

[1] Department of Neurobiology, Harvard Medical School, Boston, United States;The Vollum Institute, Oregon Health & Science University, Portland, United States;

关键词: dopamine;    RIM;    active zone;    secretion;    somatodendritic release;    neuromodulation;   

DOI  :  10.7554/eLife.47972

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown