We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Dorsal raphe projection inhibits the excitatory inputs on lateral habenula and alleviates depressive behaviors in rats.
- Authors
Zhang, Hai; Li, Kuan; Chen, Hong-Sheng; Gao, Shuang-Qi; Xia, Zhi-Xuan; Zhang, Jie-Ting; Wang, Fang; Chen, Jian-Guo
- Abstract
Hypofunction of the serotonergic (5-HT) system has close relationship with the symptoms in major depressive disorders (MDD), however, the underlying neural circuitry mechanisms are not fully understood. Lateral habenula (LHb) plays a crucial role in aversive behaviors and is activated in conditions of depression. It has been reported that 5-HT inhibits the excitability of LHb neurons, leading to the hypothesis that decreased transmission of 5-HT would elevate the activity of LHb and therefore mediates depressive symptoms. Using retrograde tract tracing with cholera toxin subunit B, we find that dorsal raphe nucleus (DRN) sends primary 5-HT projection to the LHb. In vitro slice patch-clamp recording reveals that opto-stimulation of DRN inputs to the LHb suppresses the frequency of miniature excitatory postsynaptic current, while increases paired pulse ratio in LHb neurons, indicating 5-HT projection presynaptically suppresses the excitability of LHb neurons. In chronic unpredictable mild stress (CUMS) rat model of depression, optogenetic stimulation of DRN-LHb projection alleviates the depressive symptoms in CUMS models. Meanwhile, opto-inhibition of this circuit results in elevated c-fos expression in LHb and induces depression-like behaviors. This study demonstrates that the 5-HT projection from DRN to LHb suppresses the excitability of LHb neurons, and hypofunction of 5-HT transmission induces depressive behavior via the activation of LHb. Our results reveal the functional connectivity of DRN-LHb circuit and its antidepressant action, which may provide a novel target for the treatment of depression.
- Subjects
MENTAL depression; RAPHE nuclei; NEURONS; NEURAL stimulation; CHOLERA toxin
- Publication
Brain Structure & Function, 2018, Vol 223, Issue 5, p2243
- ISSN
1863-2653
- Publication type
Article
- DOI
10.1007/s00429-018-1623-3