Site Independence of EPSP Time Course Is Mediated by Dendritic<i>I</i> _h in Neocortical Pyramidal Neurons

TLDR

Neocortical layer 5 pyramidal neurons have long apical dendrites that receive much of their excitatory input, and passive models predict that EPSPs should be prolonged as they travel to the soma, but dendritic voltage‑activated channels may alter this propagation. The study aims to characterize the properties and distribution of I(h) channels in the axon, soma, and apical dendrites of layer 5 pyramidal neurons and assess their impact on EPSP time course. We mapped I(h) channel density along dendrites and measured EPSP propagation to determine how these channels influence somatic EPSP dynamics. Dendritic I(h) channel density increases linearly with distance from the soma, creating site‑independent EPSP time courses at the soma up to 435 µm, normalizing temporal summation that collapses when I(h) channels are blocked, revealing enhanced temporal summation mediated by sodium channels.

Abstract

Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of I(h) channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 microm) in the density of dendritic I(h) channels with distance from soma. This nonuniform distribution of I(h) channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 microm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of I(h) channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic I(h) channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.