mPFC Innervation of the Basal Forebrain

The medial prefrontal cortex (mPFC) regulates affective and motivational behaviors through its projections to subcortical targets. In this study, using neural activity mapping, molecular characterization, and pathway-specific optogenetic manipulations, we investigated the functional role of mPFC projections to the basal forebrain (BF). Selective activation of infralimbic (IL) projections to the BF, which predominantly terminate in the ventral pallidum, increased locomotor activity, reduced freezing during fear extinction, and induced place preference. In contrast, activation of prelimbic (PrL) projections produced place avoidance without affecting activity levels or conditioned fear responses. Anatomical analyses further revealed that the majority of postsynaptic targets of these mPFC projections were hDlx-expressing inhibitory neurons in the ventral pallidum. Together, these findings identify the BF as a key target through which the prefrontal cortex regulates affective functions, with distinct IL and PrL pathways differentially shaping motivational state, valence processing, and fear memory.

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