The medial prefrontal cortex (MPF) regulates autonomic and neuroendocrine responses to stress1,2 and coordinates goal-directed behaviours such as attention, decision-making and social interactions3–8. However, the underlying mechanisms remain unclear due to incomplete circuit-level MPF characterization7. Here, using integrated neuroanatomical, physiological and behavioural approaches, we construct a comprehensive wiring diagram of the MPF, focused on the dorsal peduncular area (DP)—a poorly understood prefrontal area. We identify its deep (DPd) and superficial (DPs) layers, along with the infralimbic area, as major components of the visceromotor cortex that directly project to hypothalamic and brainstem structures to govern neuroendocrine, sympathetic and parasympathetic output. Notably, the DP functions as a network hub integrating diverse cortical inputs and modulating goal-directed behaviour through a largely unidirectional cortical information flow. On the basis of the mesoscale MPF connectome, we propose a unified network model in which distinct MPF areas orchestrate physiological and behavioural responses to internal and external stimuli.
