Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition in the Prefrontal Cortex

Excitation and inhibition are highly specific in the cortex, with distinct synaptic connections made onto subtypes of projection neurons. The functional consequences of this selective connectivity depend on both synaptic strength and the intrinsic properties of targeted neurons but remain poorly understood. Here, we examine responses to callosal inputs at cortico-cortical (CC) and cortico-thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We find callosally evoked excitation and feedforward inhibition are much stronger at CT neurons compared to neighboring CC neurons. Elevated inhibition at CT neurons reflects biased synaptic inputs from parvalbumin and somatostatin positive interneurons. The intrinsic properties of postsynaptic targets equalize excitatory and inhibitory response amplitudes but selectively accelerate decays at CT neurons. Feedforward inhibition further reduces response amplitude and balances action potential firing across these projection neurons. Our findings highlight the synaptic and cellular mechanisms regulating callosal recruitment of layer 5 microcircuits in PFC. Anastasiades et al. explore the functional significance of differences in synaptic connectivity and intrinsic physiology at two classes of layer 5 projection neurons in the prefrontal cortex (PFC). They find subthreshold and suprathreshold responses depend on cell-type-specific connectivity and physiology, which combine to influence synaptic responses and evoked firing.