Cell Reports
Volume 13, Issue 9, 1 December 2015, Pages 1965-1976
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Article
Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

https://doi.org/10.1016/j.celrep.2015.10.061Get rights and content
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Highlights

  • Increasing 5-HT neuronal activity increases anxiety-like behavior

  • Low DR/MR 5-HTergic activity correlates with altered emotional behavior in PNFLX mice

  • Reducing 5-HT neuronal activity normalizes emotional behavior in PNFLX mice

  • MR and DR 5-HT neuronal activity exert opposing consequences on floating behavior

Summary

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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).