The residence of synaptically released dopamine on D2 autoreceptors

Cell Rep. 2021 Aug 3;36(5):109465. doi: 10.1016/j.celrep.2021.109465.

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 less well understood is the spatial and temporal kinetics of transmitter and receptor interaction. The present work uses 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 blocks receptors in milliseconds such that the time course of dopamine/receptor interaction is 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.

Keywords: G Protein Coupled Receptors; GIRK; Substantia Nigra; caged-sulpiride; dendritic release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism*
  • Extracellular Space / metabolism
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
  • Kinetics
  • Light
  • Male
  • Mice, Inbred C57BL
  • Photolysis
  • Receptors, Dopamine D2 / metabolism*
  • Synapses / metabolism*
  • Time Factors

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Receptors, Dopamine D2
  • Dopamine