School of Medicine Publications and Presentations

Document Type

Article

Publication Date

1-2023

Abstract

Although we understand how serotonin receptors function at the single-cell level, what role different serotonin receptors play in regulating brain-wide activity and, in turn, human behavior, remains unknown. Here, we developed transcriptomic–neuroimaging mapping to characterize brain-wide functional signatures associated with specific serotonin receptors: serotonin receptor networks (SRNs). Probing SRNs with optogenetics–functional magnetic resonance imaging (MRI) and pharmacology in mice, we show that activation of dorsal raphe serotonin neurons differentially modulates the amplitude and functional connectivity of different SRNs, showing that receptors’ spatial distributions can confer specificity not only at the local, but also at the brain-wide, network level. In humans, using resting-state functional MRI, SRNs replicate established divisions of serotonin effects on impulsivity and negative biases. These results provide compelling evidence that heterogeneous brain-wide distributions of different serotonin receptor types may underpin behaviorally distinct modes of serotonin regulation. This suggests that serotonin neurons may regulate multiple aspects of human behavior via modulation of large-scale receptor networks.

Comments

Copyright © 2022, The Author(s)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Nature Neuroscience

DOI

10.1038/s41593-022-01213-3

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics

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