HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species.

The physiological properties of human and rodent neurons differ, yet the extent to which these differences reflect human specializations is often unclear. Compared with their rodent counterparts, human supragranular pyramidal neurons possess enriched Hyperpolarization-activated Cyclic Nucleotide-gated channel (HCN channel)-dependent intrinsic membrane properties and a related sensitivity to synaptic inputs containing delta/theta band frequencies. Here we test whether other primate species possess enriched HCN channel dependent membrane properties. We observe ubiquitous HCN1 subunit gene expression in supragranular glutamatergic neurons across New World Monkeys, Old-World Monkeys, and great apes in single nucleus RNA-sequencing datasets. Using Patch-seq recordings from acute and cultured brain slices, we describe robust HCN channel-dependent physiological properties in supragranular pyramidal neurons in a species of New-World monkey (Saimiri sciureus) and two species of Old-World Monkey (Macaca mulatta, Macaca nemestrina). In both human and macaque neocortex, HCN channel-related intrinsic properties increase in magnitude with increasing laminar depth, especially in the L2/3 IT_1 transcriptomic cell type. Within this type, HCN dependent properties are more pronounced in macaque than human neurons. These findings indicate that HCN channel-governed membrane properties and sensitivity to delta/theta band frequencies are roughly conserved in supragranular pyramidal neurons across at least 36 million years of primate evolution.