Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum

Abstract The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, vitro electrophysiology, chemogenetics fiber photometry rats engaged a 5-choice serial reaction time task to characterize dmPFC vmPFC outputs thalamic striatal subdomains. We identify four spatially segregated projection neuron populations the mPFC. Using show that these projections distinctly encode Postsynaptic neurons differentially process synaptic inputs from vmPFC, highlighting potentially amplify pathways control of Chemogenetic silencing lateral mediodorsal thalamus subregions oppositely regulate control. In addition, projecting striatum divergently Collectively, output targeting anatomically functionally bi-directional command