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Cell Rep. 2015 Dec 1;13(9):1965-76. doi: 10.1016/j.celrep.2015.10.061. Epub 2015 Nov 19.

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors.

Author information

1
Department of Psychiatry, Columbia University, New York, NY 10032, USA.
2
New York State Psychiatric Institute, New York, NY 10032, USA.
3
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
4
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
5
Department of Psychiatry, Columbia University, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
6
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.

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.

PMID:
26655908
PMCID:
PMC4756479
DOI:
10.1016/j.celrep.2015.10.061
[Indexed for MEDLINE]
Free PMC Article

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