A medial habenula neural circuit controlling anxiety-like behaviors in response to acute stress

Anxiety is characterized by worried thoughts and an aversion to immediate threats. While the neural circuits underlying anxiety have been studied, the underlying circuit mechanisms remain largely unknown. Here, we report that the activity of tachykinin-expressing (Tac1) neurons in the medial habenula (MHb) is decreased and excitatory projections from these neurons are inhibited in response to acute stress in mice. Activation of interfascicular nucleus (IF)^GLUT→MHb^Tac1 projections ameliorates anxiety-like behaviors in stressed mice. Moreover, MHb^Tac1 neurons send excitatory projections to the lateral part of the interpeduncular nucleus (IPL), regulating the activity of Tac1-projecting IPL neurons and anxiety-like behaviors in stressed mice. In summary, these findings delineate the circuit involving Tac1 neurons in the MHb that mediates anxiety-like behaviors in response to acute stress in mice.