Although activation of microglial cells is critical in developing
brain disorders, their role in anxiety-like behaviors in
pain is still vague. This study indicates that alteration of microglia's neuronal spine engulfment capacity in ventral zona incerta (ZI V ) leads to significant
pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud's Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZI V (ZI V
GABA ) in brain slices, we observed decreased activity in ZIv
GABA and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZI V
GABA of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZI V
GABA significantly relieved
pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZI V
GABA induced
pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZI V Microglia and increased microglial engulfment of spines in ZI V of CFA1D mice. Furthermore,
pain sensitization and anxiety-like behaviors were reversed when the ZI V Microglia of CFA1D-treated mice were chemically inhibited by intra-ZI V
minocycline injection, accompanied by the recovery of decreased ZI V
GABA excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZI V
GABA , thus promoting the development of anxiety-like behaviors in
acute pain.