Abstract
Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have a reward-related component. To date, research has focused on understanding these effects by measuring or manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior, however they leave open many questions about the timing and location of serotonin’s actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR Activation Based sensor for serotonin (GRAB-5HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without co-release confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS.
Significance Statement Serotonin influences many reward-related phenotypes including those dysregulated in a number of psychiatric and neurological disorders. A large amount of research has focused on the role of dopamine in mediating striatal reward circuits, though we know that serotonin has the potential to modulate striatal circuitry and reward behaviors. Using the recently developed serotonin biosensor, GRAB-5-HT, we were able to resolve the timescale and components of reward that are encoded by striatal serotonin. Our results show that serotonin is released in anticipation of a reward and also to a cue that predicts a reward, and the long duration signal is graded by extrinsic and subjective value.
Footnotes
The authors declare no competing financial interests
Funding from NIMH R01MH126178. The authors would like to thank members of the Nautiyal and Smith labs for their helpful discussions.
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