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Papers of the Week


Papers: 23 Sep 2023 - 29 Sep 2023

RESEARCH TYPE:
Basic Science, Psychology


Animal Studies, Neurobiology

PAIN TYPE:
Neuropathic Pain, Psychological/Comorbidities


2023 Sep 21


Cell Rep


37738124


42


10

Editor's Pick

The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain.

Authors

Wang XY, Xu X, Chen R, Jia WB, Xu PF, Liu XQ, Zhang Y, Liu XF, Zhang Y

Abstract

Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input to the lateral habenula (LHb) has been implicated in the pathophysiology of depression. However, the contribution of inhibitory transmission remains unclear. Here, we dissect an inhibitory projection from the sensory thalamic reticular nucleus (sTRN) to the LHb, which is activated by acute aversive stimuli. However, chronic restraint stress (CRS) weakens sTRN-LHb synaptic strength, and this synaptic attenuation is indispensable for CRS-induced LHb neural hyperactivity and depression onset. Moreover, artificially inhibiting the sTRN-LHb circuit induces depressive-like behaviors in healthy mice, while enhancing this circuit relieves depression induced by both chronic stress and chronic pain. Intriguingly, neither neuropathic pain nor comorbid mechanical hypersensitivity in chronic stress is affected by this pathway. Altogether, our study demonstrates an sTRN-LHb circuit in establishing and modulating depression, thus shedding light on potential therapeutic targets for preventing or managing depression.