A mismatch between striatal cholinergic pauses and dopaminergic reward prediction errors

Abstract

Movement, motivation and reward-related learning depend strongly on striatal dopamine and acetylcholine. These neuromodulators each regulate the other, and disturbances to their coordinated signals contribute to human disorders ranging from Parkinsons Disease to depression and addiction. Pauses in the firing of cholinergic interneurons (CINs) are thought to coincide with pulses in dopamine release that encode reward prediction errors (RPEs), together shaping synaptic plasticity and thereby learning. However, such models are based upon recordings from unidentified neurons, and do not incorporate the distinct characteristics of striatal subregions. Here we compare the firing of identified, individual CINs to dopamine release as unrestrained rats performed a probabilistic decision-making task. The relationships between CIN spiking, dopamine release, and behavior varied strongly by subregion. In dorsal-lateral striatum a Go! cue evoked burst-pause CIN spiking, quickly followed by a very brief (~150ms) dopamine pulse that was unrelated to RPE. In dorsal-medial striatum the same cue evoked only a CIN pause; this pause was curtailed by a movement-selective rebound in firing. Finally in ventral striatum a reward cue evoked slower, RPE-coding increases in both dopamine and CIN firing, without any distinct pause. Our results demonstrate a spatial and temporal dissociation between CIN pauses and dopamine RPE signals, and will inform new models of striatal microcircuits and their contributions to behavior.