The Residence of Synaptically Released Dopamine on D2-Autoreceptors

Abstract

Neuromodulation mediated by synaptically released endogenous transmitters acting in G protein coupled receptors (GPCRs) is slow primarily because of multistep downstream signaling. What is not known is the spatial and temporal kinetics of transmitter and receptor interaction. The present work used the combination of the dopamine sensor, dLight, to detect the spatial release and diffusion of dopamine and a caged form of a D2-dopamine receptor antagonist, CyHQ-sulpiride, to rapidly block the D2-autoreceptors. Photoactivation of the CyHQ-sulpiride blocked receptors in milliseconds such that the time course of dopamine/receptor interaction was mapped onto the downstream signaling. The results show that highly localized release, but not dopamine diffusion, defines the time course of the functional interaction between dopamine and D2-autoreceptors, which determines downstream inhibition.