Site independence of EPSP time course is mediated by dendritic I-h in neocortical pyramidal neurons

Neocortical layer 5 pyramidal neurons possess long apical dendrites that re ceive a significant portion of the neurons excitatory synaptic input. Passi ve neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as t hey propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we invest igate the properties and distribution of I-h channels in the axon, soma, an d apical dendrites of neocortical layer 5 pyramidal neurons, acid their eff ect on EPSP time course. We find a linear increase (9 pA/100 mu m) in the d ensity of dendritic I-h, channels with distance from soma. This nonuniform distribution of I-h channels generates site independence of EPSP time cours e, such that the half-width at the soma of distally generated EPSPs (up to 435 mu m from soma) was similar to somatically generated EPSPs. As a coroll ary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharma cological blockade of I-h channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensit ive sodium channels. These data indicate that an increasing density of apic al dendritic I-h channels mitigates the influence of cable filtering on som atic EPSP time course and temporal summation in neocortical layer 5 pyramid al neurons.