Diversity amongst human cortical pyramidal neurons revealed via their sag currents and frequency preferences

In the human neocortex coherent interlaminar theta oscillations are driven by deep cortical layers, suggesting neurons in these layers exhibit distinct electrophysiological properties. To characterize this potential distinctiveness, we use in vitro whole-cell recordings from cortical layers 2 and 3 (L2&3), layer 3c (L3c) and layer 5 (L5) of the human cortex. Across all layers we observe notable heterogeneity, indicating human cortical pyramidal neurons are an electrophysiologically diverse population. L5 pyramidal cells are the most excitable of these neurons and exhibit the most prominent sag current (abolished by blockade of the hyperpolarization activated cation current, I-h). While subthreshold resonance is more common in L3c and L5, we rarely observe this resonance at frequencies greater than 2Hz. However, the frequency dependent gain of L5 neurons reveals they are most adept at tracking both delta and theta frequency inputs, a unique feature that may indirectly be important for the generation of cortical theta oscillations. The unique biophysical properties of human cortical neurons that may underlie interlaminar communication are explored. With a focus on I-h and layers 2&3, 3c, and 5, the authors show that L5 pyramidal neurons are better adapted than their superficial layer counterparts to track delta and theta frequency inputs.

Automated summary

The study reveals the diverse electrophysiological properties of human cortical pyramidal neurons, with L5 pyramidal cells being the most excitable and exhibiting the most prominent sag current. While subthreshold resonance is more common in L3c and L5, L5 neurons are uniquely adept at tracking both delta and theta frequency inputs. These biophysical properties may play a crucial role in the generation of cortical theta oscillations.