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Publication : Median raphe serotonin neurons promote anxiety-like behavior via inputs to the dorsal hippocampus.

First Author  Abela AR Year  2020
Journal  Neuropharmacology Volume  168
Pages  107985 PubMed ID  32035145
Mgi Jnum  J:365826 Mgi Id  MGI:8188291
Doi  10.1016/j.neuropharm.2020.107985 Citation  Abela AR, et al. (2020) Median raphe serotonin neurons promote anxiety-like behavior via inputs to the dorsal hippocampus. Neuropharmacology 168:107985
abstractText  Anxiety disorders may be mediated in part by disruptions in serotonin (5-hydroxytryptamine, 5-HT) system function. Behavioral measures of approach-avoidance conflict suggest that serotonin neurons within the median raphe nucleus (MRN) promote an anxiogenic state, and some evidence indicates this may be mediated by serotonergic signaling within the dorsal hippocampus. Here, we test this hypothesis using an optogenetic approach to examine the contribution of MRN 5-HT neurons and 5-HT innervation of the dorsal hippocampus (dHC) to anxiety-like behaviours in female mice. Mice expressing the excitatory opsin ChR2 were generated by crossing the ePet-cre serotonergic cre-driver line with the conditional Ai32 ChR2 reporter line, resulting in selective expression of ChR2 in 5-HT neurons. Electrophysiological recordings confirmed that this approach enabled reliable optogenetic stimulation of MRN 5-HT neurons, and this stimulation produced downstream 5-HT release in the dHC as measured by in vivo microdialysis. Optogenetic stimulation of the MRN elicited behavioral responses indicative of an anxiogenic effect in three behavioural tests: novelty-suppressed feeding, marble burying and exploration on the elevated-plus maze. These effects were shown to be behaviourally-specific. Stimulation of 5-HT terminals in the dHC recapitulated the anxiety-like behaviour in the novelty-suppressed feeding and marble burying tests. These results show that activation of 5-HT efferents from the MRN rapidly induces expression of anxiety-like behaviour, in part via projections to the dHC. These findings reveal an important neural circuit implicated in the expression of anxiety in female mice.
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