Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs

Publication date: 13 December 2016
Source:Cell Reports, Volume 17, Issue 11
Author(s): Celia Kjaerby, Jegath Athilingam, Sarah E. Robinson, Jillian Iafrati, Vikaas S. Sohal
Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4–12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function, including anxiety-related behaviors.

Graphical abstract

Teaser

Kjaerby et al. find that serotonin acts presynaptically to suppress callosal and ventral hippocampal inputs to layer V of prefrontal cortex through 5-HT1B receptors. Infusion of a 5-HT1B agonist suppresses prefrontal theta oscillations and anxiety-related avoidance behavior, suggesting that prefrontal serotonin can act as a gatekeeper to regulate such behavior.


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