Defensive brain states, such as fear and anxiety, evolved as mediators of multidimensional reactions to threat, which encompass integrated autonomic, behavioral and endocrine responses. Multiple interconnected brain structures have been involved in defensive reactions, in particular the midbrain’s periaqueductal gray (PAG), the amygdala, and different cortical areas such as the auditory and prefrontal cortices, together processing information at multiple levels of the neuraxis. Several roles pertaining to higher-order threat processing have been assigned to the medial prefrontal cortex (mPFC), including the encoding of threat imminence, the extinction of fear memory and the expression of defensive behaviors​. Yet, the exact relationship between mPFC activity and the generation of integrated defensive states remains unclear.We recently found that environmental threat levels can generate a latent physiological state (macrostate) that underlies changes in the expression of stereotypical defensive cardio-behavioural reactions (microstates). We hypothesized that the mPFC, through the integration of multimodal information, would be required to generate and adjust a resulting “macrostate signal”.Using viral tracing strategies as well as behavioral and electrocardiographic recordings combined with concomitant one-photon calcium imaging of PFC neuronal activity in freely moving mice, we unveil PFC activity correlates of cardio-behavioral defensive states. In addition, targeted optogenetic approaches to manipulate the activity of microstate-generator Chx10+ PAG neurons shed light on the functional relevance of corresponding circuit elements.Altogether, our work contributes to a mechanistic understanding of the integration and orchestration of different defensive state elements within PFC circuits.