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 footshock delivery and footshock-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.