Intratelencephalic neurons in the medial prefrontal cortex mediate the acquisition of goal-directed actions

The medial prefrontal cortex (mPFC) and its connections with the posterior dorsomedial striatum are implicated in goal-directed learning, but the specific mPFC cell types involved have not been clearly established. The current study investigates mPFC intratelencephalic (IT) and pyramidal tract (PT) neuron involvement in goal-directed learning. In Cre-driver mouse lines, we map bilaterally projecting IT neurons and unilaterally projecting PT neurons from mPFC to dorsal striatum and show that chemogenetic inhibition of IT, but not PT neurons, attenuates goal-directed learning. We then demonstrate training-induced elevations in pERK signaling in IT neurons, which is transient in superficial mPFC layers, and more persistent in deeper layers. This is associated with plasticity in deep layer IT neurons, reflected by a shift toward excitatory over inhibitory synaptic inputs. Together, these data suggest that goal-directed learning influences synaptic input and downstream plasticity markers in mPFC IT neurons, and this functionally contributes to goal-directed learning.