Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24733892.
- Also identified by DOI 10.1073/pnas.1321576111 and PMC identifier 4035925.
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Abstract
Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.
Medical subject headings
- Anxiety
- Feedback, Physiological
- GABAergic Neurons
- GTP-Binding Protein alpha Subunits, Gq-G11
- Neural Inhibition
- Receptor, Serotonin, 5-HT2C
- Serotonin