Gq/5-HT2creceptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice
Copyright policy )Gq/5-HT2creceptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice
SignificanceSerotonin is an important modulator of anxious states. Serotonergic neurotransmission in the dorsal raphe nuclei is known to be regulated by different presynaptic and postsynaptic feedback mechanisms involving G protein-coupled receptor signals, but the influence of such feedback mechanisms on anxiety-related behavior has not been investigated until now. We found that optogenetic activation of the Gq-coupled receptor signals in 5-HT2creceptor locations in GABAergic neurons in dorsal raphe nuclei decreases the activity of 5-HT neurons and relieves anxiety in mice. 5-HT2creceptors are drug targets for mental disorders. Our results demonstrate a previously unidentified negative feedback mechanism by 5-HT2c/Gq signals for the fine-tuning of anxiety behavior, and point to a promising therapeutic strategy for treating anxiety-related disorders.
- Case Western Reserve University United States
- Ruhr University Bochum Germany
Feedback, Physiological, Serotonin, Light, Intracellular Space, Rod Opsins, Action Potentials, Down-Regulation, Neural Inhibition, Anxiety, Protein Structure, Tertiary, Optogenetics, Mice, HEK293 Cells, Receptor, Serotonin, 5-HT2C, Animals, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Raphe Nuclei, Calcium, GABAergic Neurons
Feedback, Physiological, Serotonin, Light, Intracellular Space, Rod Opsins, Action Potentials, Down-Regulation, Neural Inhibition, Anxiety, Protein Structure, Tertiary, Optogenetics, Mice, HEK293 Cells, Receptor, Serotonin, 5-HT2C, Animals, GTP-Binding Protein alpha Subunits, Gq-G11, Humans, Raphe Nuclei, Calcium, GABAergic Neurons
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