title: Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.
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.
authors.affiliation: Department of General Zoology and Neurobiology, Ruhr University Bochum, D-44780 Bochum, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Spoida
authors.forename: Olivia A
authors.initials: OA
authors.lastname: Masseck
authors.forename: Evan S
authors.initials: ES
authors.lastname: Deneris
authors.forename: Stefan
authors.initials: S
authors.lastname: Herlitze
mesh_terms: D000200:Action Potentials / Q000528:radiation effects; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation / Q000528:radiation effects; D025461:Feedback, Physiological / Q000528:radiation effects; D059330:GABAergic Neurons / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism / Q000528:radiation effects; D008027:Light; D051379:Mice; D009433:Neural Inhibition / Q000528:radiation effects; D062308:Optogenetics; D017434:Protein Structure, Tertiary; D011903:Raphe Nuclei / Q000378:metabolism / Q000528:radiation effects; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D017299:Rod Opsins / Q000737:chemistry / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D000099210:Melanopsin
chemical_list: D002118:Calcium; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044405:Receptor, Serotonin, 5-HT2C; D017299:Rod Opsins; D012701:Serotonin; D000099210:Melanopsin
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1217-21
references.pmid: 15653769
references.citation: Neurosci Res. 2013 Jan;75(1):23-8
references.pmid: 22868039
references.citation: Br J Pharmacol. 2009 Nov;158(6):1477-85
references.pmid: 19845681
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jun;30(4):565-85
references.pmid: 16436311
references.citation: J Comp Neurol. 2007 Nov 20;505(3):314-35
references.pmid: 17879281
references.citation: Behav Brain Res. 2003 Jun 16;142(1-2):125-33
references.pmid: 12798273
references.citation: Neuroscience. 2003;122(1):193-204
references.pmid: 14596860
references.citation: Brain Res Bull. 1992 Dec;29(6):943-8
references.pmid: 1473026
references.citation: Neuroscience. 2010 Dec 15;171(3):734-46
references.pmid: 20816924
references.citation: Neuropharmacology. 1988 Oct;27(10):993-1001
references.pmid: 2467224
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16472-7
references.pmid: 16251278
references.citation: J Pharmacol Exp Ther. 1988 Sep;246(3):924-8
references.pmid: 2843634
references.citation: J Biol Chem. 2010 Oct 1;285(40):30825-36
references.pmid: 20643652
references.citation: Stress. 2005 Dec;8(4):233-46
references.pmid: 16423712
references.citation: Neuropharmacology. 1999 Aug;38(8):1083-152
references.pmid: 10462127
references.citation: Br J Pharmacol. 2006 Dec;149(7):861-9
references.pmid: 17043669
references.citation: Therapie. 2005 Sep-Oct;60(5):441-60
references.pmid: 16433010
references.citation: Neurochem Res. 2000 Nov;25(11):1465-73
references.pmid: 11071365
references.citation: J Neurosci. 2013 Aug 28;33(35):13978-88, 13988a
references.pmid: 23986235
references.citation: Trends Pharmacol Sci. 2007 Dec;28(12):629-36
references.pmid: 17996955
references.citation: Psychopharmacology (Berl). 2011 Feb;213(2-3):243-64
references.pmid: 21088958
references.citation: Behav Neurosci. 1995 Aug;109(4):759-66
references.pmid: 7576219
references.citation: Neuropharmacology. 2011 Sep;61(3):524-43
references.pmid: 21530552