Substance P in the lateral hypothalamic area regulates binge-like eating behaviors in mice

Binge eating disorder (BED) is the most common type of eating disorder; however, the neural circuit mechanisms underlying BED remain elusive. Here, we report that tachykinin-expressing neurons in the lateral hypothalamic area (LH^Tac1 neurons) are inhibited during binge-like eating behaviors in mice. We identified LH^Tac1 neurons as key mediators of binge-like eating behaviors and reported that the LH^Tac1→ lateral periaqueductal gray (LPAG) circuit is critical to the regulation of binge-like eating behaviors. Moreover, Substance P (SP) released by LH^Tac1 neurons modulates binge-like eating behaviors by influencing the input of glutamate to LPAG cells, which receive projections from LH^Tac1 neurons. In summary, these findings point to the SP as a key node in BED circuits.