A discrete serotonergic circuit regulates vulnerability to social stress

Abstract

Exposure to social stress and dysregulated serotonergic neurotransmission have both been implicated in the etiology of psychiatric disorders. However, the serotonergic circuit involved in stress vulnerability is still unknown. Here, we explored whether a serotonergic input from the dorsal raphe (DR) to ventral tegmental area (VTA) influences vulnerability to social stress. We identified a distinct, anatomically and functionally defined serotonergic subpopulation in the DR that projects to the VTA (5-HT DR→VTA neurons). Moreover, we found that susceptibility to social stress decreased the firing activity of 5-HT DR→VTA neurons. Importantly, the bidirectional manipulation of 5-HT DR→VTA neurons could modulate susceptibility to social stress. Our findings reveal that the activity of 5-HT DR→VTA neurons may be an essential factor in determining individual levels of susceptibility to social stress and suggest that targeting specific serotonergic circuits may aid the development of therapies for the treatment of stress-related disorders.

A cholinergic medial septum input to medial habenula mediates generalization formation and extinction of visual aversion

“…In vitro electrophysiological recording. The methods of brain slice preparation and electrophysiological recordings were similar to those in previous studies 64,65,66 . In brief, after the full expressions of AAVs, mice were anaesthetized with isoflurane and the brains were rapidly removed and chilled in ice-cold sucrose solution containing (in mM): 40 NaCl…”

A Cholinergic Medial Septum Input to Medial Habenula Mediates Generalization Formation and Extinction of Visual Aversion

“…In vitro electrophysiological recording. The methods of brain slice preparation and electrophysiological recordings were similar to those in previous studies 64,65,66 . In brief, after the full expressions of AAVs, mice were anaesthetized with isoflurane and the brains were rapidly removed and chilled in ice-cold sucrose solution containing (in mM): 40 NaCl, 4.5 KCl, 1.25 NaH2PO4, 25 NaHCO3, 148.5 sucrose, 10 glucose, 1 ascorbic acid, 3 Na Pyruvate, 3 Myo Inositol, 0.5 CaCl2 and 7…”

Sucrose Consumption Alters Serotonin/Glutamate Co-localisation Within the Prefrontal Cortex and Hippocampus of Mice

“…However, we saw a reduction in the density of VGLUT3 boutons in both DG and PFC and a reduction in the density of 5-HT/VGLUT3 varicosities. Decreased VGLUT3 expression may be associated with susceptibility to stress ( Zou et al, 2020 ), however, the role VGLUT3 plays in sucrose consumption is unknown.…”