title: Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.
abstract: Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim test, whereas inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphé and increased median raphé serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. Furthermore, we identify opposing consequences of dorsal versus median raphé serotonergic neuron inhibition on floating behavior, together suggesting that median raphé hyperactivity increases anxiety, whereas a low dorsal/median raphé serotonergic activity ratio increases depression-like behavior. Thus, we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphé function.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Teissier
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA.
authors.forename: Alexei
authors.initials: A
authors.lastname: Chemiakine
authors.affiliation: New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Inbar
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Bagchi
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Ray
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dymecki
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: ma2362@columbia.edu.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Ansorge
mesh_terms: D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects; D002460:Cell Line; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D059326:Serotonergic Neurons / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013550:Swimming
chemical_list: D012701:Serotonin; D003024:Clozapine; C079149:clozapine N-oxide