Repetitive grooming behavior following aversive stimulus coincides with a decrease in anterior hypothalamic area activity

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Using in vivo calcium imaging in mice, we observed that AHA neuronal activity increases during foot shock delivery and foot-shock associated auditory cues. We found that following shock-induced increases in AHA activity, a decrease in activity coincides with the onset of grooming behavior. Next, we optogenetically activated the projections from the ventromedial hypothalamus (VMH) to the AHA and observed that photoactivation of the VMH→AHA pathway drives avoidance. Interestingly, repetitive grooming behavior occurs following cessation of stimulation. To identify changes in brain-wide activity patterns that occur due to optogenetic VMH→AHA stimulation, we combined optogenetic stimulation with positron emission tomography (PET) based metabolic mapping. This approach revealed the amygdala as a downstream area activated by the stimulation of this pathway. Our findings show that the rise and fall of AHA neuronal activity triggers repetitive grooming behavior following learned fear and optogenetic stimulation. In addition, activation of the VMH→AHA pathway triggers changes in the activity patterns of downstream brain regions that are reported to be associated with displacement grooming.Significance statement This work identifies an association between grooming behavior and anterior hypothalamic area (AHA) activity patterns. Regardless of whether the activation of the AHA is initiated by shock-associated conditioned fear or optogenetic stimulation of excitatory inputs from the ventromedial hypothalamus, repetitive self-grooming behavior emerges during the post-activation decrease in activity. Further, this work identifies that even in anesthetized mice, AHA activation serves as a trigger for downstream network changes in the amygdala and striatum, which are associated with repetitive behavior. Together, this work positions the anterior hypothalamic area as a potential etiological factor to be considered at the intersection of fear experience and subsequent repetitive behaviors.