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Zadarex OP t1_jdwemof wrote


  • Forced loss lowers social ranks and induces depressive-like behaviors
  • Forced loss generates negative reward prediction error
  • Forced loss but not natural loss activates LH-LHb circuit and induces LHb bursting
  • LHb burst firing inhibits mPFC and reinforces subordination


Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce depressive-like behaviors. These rank-decline-associated depressive-like behaviors can be reversed by regaining social status. In vivo fiber photometry and single-unit electrophysiological recording show that forced loss, but not natural loss, generates negative reward prediction error (RPE). Through the lateral hypothalamus, the RPE strongly activates the brain’s anti-reward center, the lateral habenula (LHb). LHb activation inhibits the medial prefrontal cortex (mPFC) that controls social competitiveness and reinforces retreats in contests. These results reveal the core neural mechanisms mutually promoting social status loss and depressive behaviors. The intertwined neuronal signaling controlling mPFC and LHb activities provides a mechanistic foundation for the crosstalk between social mobility and psychological disorder, unveiling a promising target for intervention.


Naxela t1_jdy8ygf wrote

This is absolutely fascinating, thank for you sharing. Very relevant to the fields I work in, and I haven't been familiar as much with Dr. Hu's work as I apparently should be.