Mechanically evoked defensive attack is controlled by GABAergic neurons in the anterior hypothalamic nucleus.

Innate defensive behaviors triggered by environmental threats are important for animal survival. Among these behaviors, defensive attack toward threatening stimuli (for example, predators) is often the last line of defense. How the brain regulates defensive attack remains poorly understood. Here we show that noxious mechanical force in an inescapable context is a key stimulus for triggering defensive attack in laboratory mice. Mechanically evoked defensive attacks were abrogated by photoinhibition of vGAT+ neurons in the anterior hypothalamic nucleus (AHN). The vGAT+ AHN neurons encoded the intensity of mechanical force and were innervated by brain areas relevant to pain and attack. Activation of these neurons triggered biting attacks toward a predator while suppressing ongoing behaviors. The projection from vGAT+ AHN neurons to the periaqueductal gray might be one AHN pathway participating in mechanically evoked defensive attack. Together, these data reveal that vGAT+ AHN neurons encode noxious mechanical stimuli and regulate defensive attack in mice.