Abstract
The neural substrates of anxiety are poorly understood, which hinders treatment of anxiety disorders. Here we found, αCaMKII(+) neurons in the ventral medial hypothalamic nucleus (VMH) responded to stressors with increased activity in male mice, both under physiological conditions and after repeated restraint stress. Activation of VMH αCaMKII(+) neurons were necessary and sufficient to ameliorate stress-induced anxiety. The peripheral metabolic hormone ghrelin and receptor GHS-R1a play a complex role in emotion regulation; however, the mechanism is uncertain. A delayed increase in GHS-R1a expression in VMH αCaMKII(+) neurons coincided with the development of stress-induced enhancement of anxiety-related behavior. GHS-R1a expression in VMH αCaMKII(+) neurons promoted anxiety-related behavior, whereas GHS-R1a knockdown had the opposite effect. GHS-R1a upregulation inhibited the excitability of VMH αCaMKII(+) neurons. We conclude that GHSR1a signaling drives stress-induced anxiety by shaping the activity of VMH αCaMKII(+) neurons. GHS-R1a may be a therapeutic target for treating anxiety disorders such as post-traumatic stress disorder.