Journal
BRAIN STRUCTURE & FUNCTION
Volume 223, Issue 5, Pages 2243-2258Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00429-018-1623-3
Keywords
Depression Dorsal raphe nucleus; Lateral habenula; Serotonin; Optogenetics; Chronic unpredictable mild stress
Categories
Funding
- Foundation for Innovative Research Groups of NSFC [81721005]
- National Basic Research Program of China (973 Program) [2014CB744601]
- National Key Scientific Instrument and Equipment Development Project of China [2013YQ03092306]
- PCSIRT [IRT13016]
- National Natural Science Foundation of China [81471377, 81473198, 81402913]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available