Dopamine Cells Differentially Regulate Striatal Cholinergic Transmission across Regions through Corelease of Dopamine and Glutamate

Abstract

Summary: The balance of dopamine and acetylcholine in the dorsal striatum is critical for motor and learning functions. Midbrain dopamine cells and local cholinergic interneurons (ChIs) densely innervate the striatum and have strong reciprocal actions on each other. Although dopamine inputs regulate ChIs, the functional consequences of dopamine neuron activity across dorsal striatal regions is poorly understood. Here, we find that midbrain dopamine neurons drive pauses in the firing of dorsomedial ChIs but robust bursts in dorsolateral ChIs. Pauses are mediated by dopamine D2 receptors, while bursts are driven by glutamate corelease and activation of a mGluR-mediated excitatory conductance. We find the frequency of muscarinic cholinergic transmission to medium spiny neurons is greater in the dorsomedial striatum. This regional variation in transmission is moderated by the different actions of dopamine and glutamate corelease. These results delineate a mechanism by which dopamine inputs maintain consistent levels of cholinergic activity across the dorsal striatum. : Cai and Ford identify regional differences in the extent of ACh transmission onto direct pathway medium spiny neurons between the dorsomedial and the dorsolateral striatum. These differences were normalized by SNc inputs, which had opposing actions on the firing of cholinergic interneurons in each region. Keywords: dopamine, GPCR, basal ganglia, striatum, accumens, metabotrophic, Parkinson’s disease, mGluR