Action Potential Firing Patterns Regulate Dopamine Release via Voltage-Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo.

ABSTRACT: Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown. Here by using in vivo and ex vivo models, it is shown that the AP frequency per se modulates DA release through the D2 receptor (D2R), which contributes up to 50% of total DA release. D2R has a voltage-sensing site at D131 and can be deactivated in a frequency-dependent manner by membrane depolarization. This voltage-dependent D2R inhibition of DA release is mediated via the facilitation of voltage-gated Ca²⁺ channels (VGCCs). Collectively, this work establishes a novel mechani

SUBMITTER: Sun X 

PROVIDER: S-EPMC11831442 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature