Local administration of monoclonal antibody against HMGB1 (anti-HMGB1 mAb) and exogenous ds-HMGB1 (the pro-inflammatory form of HMGB1) into the mPFC demonstrated the determinant role of HMGB1 in anxiety, which was supported by that optogenetic inhibition of mPFC pyramidal neurons alleviated anxiety. Here, HMGB1 is linked to Anxiety.