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.
Recommended Citation
Salvan, P., Fonseca, M., Winkler, A.M. et al. Serotonin regulation of behavior via large-scale neuromodulation of serotonin receptor networks. Nat Neurosci 26, 53–63 (2023). https://doi.org/10.1038/s41593-022-01213-3
Creative Commons 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
Comments
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