Meaningful silences: how dopamine listens to the ACh pause

Mesostriatal dopaminergic neurons (DANs) and striatal cholinergic neurons (tonically active neurons, TANs) participate in signalling the behavioural or reward-related significance of stimuli in the environment. An antagonistic balance between dopamine (DA) and ACh is well known to regulate postsynaptic signal integration in the striatum. Recent findings have revealed additional presynaptic ACh–DA interactions of previously unappreciated sophistication. Striatal ACh acts presynaptically to polarize powerfully how opposing DAN activities are transduced into DA release. Furthermore, characteristic reward-related activities of TANs and DANs are temporally coincident but differently variant with reward probability. Reward-related DA signals could therefore be governed by the concomitant activity in TANs. This article discusses the dynamic implications for DA signalling when these phenomena act in concert. TAN pauses might powerfully enhance the contrast, or salience, of DA signals offered by reward-related bursts, and even by reward omission-related pauses, in DANs. Through such mechanisms, TAN–DAN interactions would be functionally cooperative.