Discrete spatiotemporal encoding of striatal dopamine transmission

Abstract

Dopamine (DA) transmission critically regulates diverse, basal ganglia-dependent behaviors by activating distinct subtypes of G protein-coupled receptors. Spatially broad DA release has been extensively characterized, but how DA transmission affects striatal function at a subcellular scale remains poorly understood. Using 2P imaging and whole-cell electrophysiology, we defined the spatiotemporal properties of DA transmission onto striatal indirect pathway spiny projection neurons. Sparse activation of DA release sites evoked localized DA signals, producing spatially discrete, D2 receptor-mediated responses across dendrites. The spatiotemporal properties of DA receptor signaling differed between downstream intracellular pathways. We propose that membrane-delimited Gβγ signaling occurs in parallel to intracellular second messenger pathways, but on different spatial and temporal scales, providing a mechanism for precise decoding of DA signals by striatal neurons.