Pyramidal neurons in prefrontal cortex receive subtype-specific forms of excitation and inhibition.

Layer 5 pyramidal neurons comprise at least two subtypes: thick-tufted, subcortically projecting type A neurons, with prominent h-current, and thin-tufted, callosally projecting type B neurons, which lack prominent h-current. Using optogenetic stimulation, we find that these subtypes receive distinct forms of input that could subserve divergent functions. Repeatedly stimulating callosal inputs evokes progressively smaller excitatory responses in type B but not type A neurons. Callosal inputs also elicit more spikes in type A neurons. Surprisingly, these effects arise via distinct mechanisms. Differences in the dynamics of excitatory responses seem to reflect differences in presynaptic input, whereas differences in spiking depend on postsynaptic mechanisms. We also find that fast-spiking parvalbumin interneurons, but not somatostatin interneurons, preferentially inhibit type A neurons, leading to greater feedforward inhibition in this subtype. These differences may enable type A neurons to detect salient inputs that are focused in space and time, while type B neurons integrate across these dimensions.