Blunted diurnal firing in lateral habenula projections to dorsal raphe nucleus and delayed photoentrainment in stress-susceptible mice

by He Liu, Ashutosh Rastogi, Priyam Narain, Qing Xu, Merima Sabanovic, Ayesha Darwish Alhammadi, Lihua Guo, Jun-Li Cao, Hongxing Zhang, Hala Aqel, Vongai Mlambo, Rachid Rezgui, Basma Radwan, Dipesh Chaudhury Daily rhythms are disrupted in patients with mood disorders. The lateral habenula (LHb) and dorsal raphe nucleus (DRN) contribute to circadian timekeeping and regulate mood. Thus, pathophysiology in these nuclei may be responsible for aberrations in daily rhythms during mood disorders. Using the 1 5-day chronic social defeat stress (CSDS) paradigm and in vitro slice electrophysiology, we measured the effects of stress on diurnal rhythms in firing of LHb cells projecting to the DRN (cellsLHb →DRN) and unlabeled DRN cells. We also performed optogenetic experiments to investigate if increased firing in cellsLHb →DRN during exposure to a weak 7-day social defeat stress (SDS) paradigm induces stress-susceptibility. Last, we investigated whether exposure to CSDS affected the ability of mice to photoentrain to a new light –dark (LD) cycle. The cellsLHb →DRN and unlabeled DRN cells of stress-susceptible mice express greater blunted diurnal firing compared to stress-n äive (control) and stress-resilient mice. Daytime optogenetic activation of cellsLHb →DRN during SDS induces stress-susceptibility which shows the direct correlation between increased activity in this circuit and putative mood disorders. Finally, we found that stress-susceptible mice are slower, while str...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research
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