Abstract
Innate defensive responses, though primarily instinctive, must also be highly adaptive to changes in risk assessment. However, adaptive changes can become maladaptive, following severe stress, as seen in posttraumatic stress disorder (PTSD). In a series of experiments, we observed long-term changes in innate escape behavior of male mice towards a previously non-threatening stimulus following an adverse shock experience manifested as a shift in the threshold of threat response. By recording neural activity in the superior colliculus (SC) while phototagging specific responses to afferents, we established the crucial influence of input arriving at the SC from the medial prefrontal cortex (mPFC), both directly and indirectly, on escape-related activity after adverse shock experience. Inactivating these specific projections during the shock effectively abolished the observed changes. Conversely, optogenetically activating them during encounters controlled escape responses. This establishes the necessity and sufficiency of those specific mPFC inputs into the SC for adverse experience related changes in innate escape behavior.