Diurnal rhythms in cholinergic modulation of rapid dopamine signals and associative learning in the striatum

Dysregulation of biological rhythms plays a role in a wide range of psychiatric disorders. We report mechanistic insights into the rhythms of rapid dopamine signals and cholinergic interneurons (CINs) working in concert in the rodent striatum. These rhythms mediate diurnal variation in conditioned responses to reward-associated cues. We report that the dopamine signal-to-noise ratio varies according to the time of day and that phasic signals are magnified during the middle of the dark cycle in rats. We show that CINs provide the mechanism for diurnal variation in rapid dopamine signals by serving as a gain of function to the dopamine signal-to-noise ratio that adjusts across time of day. We also show that conditioned responses to reward-associated cues exhibit diurnal rhythms, with cue-directed behaviors observed exclusively midway through the dark cycle. We conclude that the rapid dopamine signaling rhythm is mediated by a diurnal rhythm in CIN activity, which influences learning and motivated behaviors across the time of day. [Display omitted] •Dopamine release magnitude exhibits diurnal rhythms•Cholinergic interneuron activity exhibits diurnal rhythms•There is diurnal variation in cholinergic interneuron modulation of dopamine release•Cue-directed conditioned responses are exclusive to rats in their dark cycle Dopamine signals in the striatum are critical for learning and motivation. Stowe et al. show that diurnal rhythms in rapid dopamine signaling in the striatum are mediated by time-of-day shifts in cholinergic interneuron control of dopamine. These systems work together to mediate time-of-day changes in learning and motivated behaviors.