Spontaneous firing and evoked pauses in the tonically active cholinergic interneurons of the striatum

Abstract The tonically active neurons (TANs) are a population of neurons scattered sparsely throughout the striatum that show intriguing patterns of firing activity during reinforcement learning. Following repeated pairings of a neutral stimulus with a primary reward, TANs develop a transient cessation of firing activity in response to the stimulus, termed the “conditioned pause response.” In tasks where specific cues are arranged to signal the probability of particular outcomes, the pause response to both cue and outcome may differ in ways that suggest the involvement of different inputs to the same neuron. Here we review the cellular properties of cholinergic interneurons and describe the response to their afferents in terms of inducing TAN-like pauses in tonic firing. Recent work has shown that thalamostriatal inputs to cholinergic neurons transiently suppress firing activity via dopamine release. Because these pauses are initiated by subcortical pathways with limited sensory processing abilities, we propose that they are an ideal correlate for the pauses observed in TANs in response to cues signaling trial initiation. On the other hand, pauses that accompany outcome presentation contain higher-level information, including an apparent sensitivity to reward prediction error. Thus, these pauses may be mediated by cortical inputs to cholinergic interneurons. Although there is evidence linking cholinergic pauses to synaptic plasticity, much remains to be discovered about the effect of this relatively sparse but influential population on the striatal learning system. This article is part of a Special Issue entitled: Function and Dysfunction of the Basal Ganglia.