Sag currents are a major contributor to human pyramidal cell intrinsic differences across cortical layers

In the human neocortex, coherent theta (~8Hz) oscillations between superficial and deep cortical layers are driven by deep layer neurons, suggesting distinct intrinsic electrophysiological properties of L5 neurons. We used in vitro whole-cell recordings to characterize pyramidal cells in layer 2/3 (L2/3), layer 3c (L3c) and layer 5 (L5) of the human neocortex. L5 pyramidal cells were more excitable and had a more prominent sag relative to L2/3 and L3c neurons that was abolished by blockade of the hyperpolarization activated cation current (Ih). We found a greater proportion of L5 and L3c neurons displaying subthreshold resonance relative to L2/3. Although no theta subthreshold resonance was observed in either L5 and L2/3 neurons, L5 neurons were more adept at tracking both delta (4Hz) and theta oscillations, the former being dependent on Ih. The unique features of human L5 neurons likely contribute to the emergence of theta oscillations in human cortical microcircuits.