Activation of the fear-responsive anterior hypothalamic area promotes avoidance and triggers compulsive grooming behavior in mice

Abstract

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Here, we first examined AHA activity patterns during fear conditioning using in vivo functional imaging. We observed that neuronal activity in the AHA increases during both foot shock delivery and foot-shock associated auditory cues. Moreover, we used a combination of optogenetics and behavioral assays to determine the functional connectivity between the ventromedial hypothalamus (VMH) and the AHA. We found that photoactivation of the VMH→AHA pathway is aversive and triggers compulsive grooming behavior. Furthermore, we observed spatial and temporal changes of grooming behavior during the periods following VMH→AHA photoactivation. Interestingly, whole brain metabolic mapping using positron emission tomography (PET) combined with optogenetic activation of the VMH→AHA pathway in anesthetized mice revealed the amygdala as a downstream area activated by the stimulation of this pathway. Together, our findings show that the AHA responds to threat and that such increases in activity are sufficient to trigger compulsive grooming behavior. Thus, our results may help to understand some neuropsychiatric disorders characterized by repetitive and compulsive behaviors.