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0 reviewsAnxiety is characterized by worried thoughts and an aversion to immediate threats. While the neural circuits underlying anxietyhave been studied, the underlying circuit mechanisms remain largely unknown. Here, we report that the activity of tachykininexpressing (Tac1) neurons in the medial habenula (MHb) is decreased and excitatory projections from these neurons are inhibitedin response to acute stress in mice. Activation of interfascicular nucleus (IF)GLUT→MHbTac1 projections ameliorates anxiety-likebehaviors in stressed mice. Moreover, MHbTac1 neurons send excitatory projections to the lateral part of the interpeduncularnucleus (IPL), regulating the activity of Tac1-projecting IPL neurons and anxiety-like behaviors in stressed mice. In summary, thesefindings delineate the circuit involving Tac1 neurons in the MHb that mediates anxiety-like behaviors in response to acute stress in1234567890();,:mice.Molecular Psychiatry;