Neural Networks of the Mouse Primary Visceromotor Cortex

The medial prefrontal cortex (MPF) regulates emotions, stress responses, and goal-directed behaviors like attention and decision-making. However, the precise mechanisms underlying MPF function remain poorly understood, largely due to an incomplete characterization of its neural circuitry. Leveraging neuroanatomical, neurophysiological, and behavioral techniques, we present a detailed wiring diagram of the MPF, with a particular focus on the dorsal peduncular area (DP), an underexplored MPF area implicated in psychological stress, fear conditioning, anxiety, depression, and opioid addiction. Our analysis identifies the deep (DPd) and superficial (DPs) layers of the DP, together with the infralimbic area (ILA), as key components of the primary visceromotor cortex, that generate monosynaptic projections to regulate neuroendocrine, sympathetic, and parasympathetic functions in distinct, yet coordinated ways. Further, we demonstrate that the DP serves as a unique network hub for unidirectional cortical information flow, that integrates diverse cortical inputs and modulates social behavior. Based on the mesoscale connectome of entire MPF, we propose a unified MPF network model that regulates different aspects of motor actions associated with goal-directed behavior. This study provides novel insights into the complex role of the MPF in orchestrating physiological and behavioral responses to environmental stimuli in mammals.