Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron

• DOI: 10.1016/j.celrep.2021.108951
• Publication Date: 2021-04-06T15:40:49Z
• Authors: Takuya Hikima; Christian R. Lee; Paul Witkovsky; Julia Chesler; Konstantin Ichtch...; Margaret E. Rice
• Keywords: Autoreceptor; Pars compacta; Neurotoxin

Somatodendritic dopamine (DA) release from midbrain DA neurons activates D2 autoreceptors on these cells to regulate their activity. However, the source of autoregulatory remains controversial. Here, we test hypothesis that a given neuron in substantia nigra pars compacta (SNc) are activated primarily by released same cell, rather than its neighbors. Voltage-clamp recording allows monitoring evoked D2-receptor-mediated inhibitory currents (D2ICs) SNc as an index release. Single-cell application antibodies Na+ channels via pipette decreases spontaneous activity recorded and attenuates D2ICs; SNAP-25, soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, also decrease D2IC amplitude. Evoked D2ICs nearly abolished light chain botulinum neurotoxin A, which cleaves whereas synaptically GABAB-receptor-mediated unaffected. Thus, somatodendritic autoinhibits releases it.