Local and propagated dendritic action potentials evoked by glutamate iontophoresis on rat neocortical pyramidal neurons.

Iontophoresis of glutamate at sites on the apical dendrite 278-555 microm from the somata of rat neocortical pyramidal neurons evoked low-threshold, small, slow spikes and/or large, fast spikes in 71% of recorded cells. The amplitude of the small, slow spikes recorded at the soma averaged 9.1 mV, and their apparent threshold was <10 mV positive to resting potential. Both their amplitude and their apparent threshold decreased as the iontophoretic site was moved farther from the soma. These spikes were not abolished by somatic hyperpolarization. When the somata of cells displaying these small spikes were voltage clamped at membrane potentials that prevented somatic or axonic firing, corresponding current spikes could be evoked all-or-none by dendritic depolarization, indicating that the small, slow spikes arose in the dendrite. Similar responses were not observed during somatic depolarization evoked by current pulses or glutamate iontophoresis. These small, slow spikes were abolished by blocking voltage-gated Ca2+ channels but not by blocking Na+ channels or N-methyl-D-aspartate receptors. We conclude that these Ca2+ spikes occurred in a spatially restricted region of the dendrite and were not actively propagated to the soma. In the presence of 10 mM tetraethylammonium chloride, the amplitudes of the iontophoretically evoked Ca2+ spikes were large, similar to those of the Ca2+ spikes evoked by somatic current injection, but their apparent thresholds were 63% lower. We conclude that dendritic K+ channels normally prevent the active propagation of Ca2+ spikes along the dendrite. In 36% of recorded cells dendritic glutamate iontophoresis evoked a Na+ spike with an apparent threshold 63% lower than those evoked by somatic current injection or somatic glutamate iontophoresis. Blockade of these low-threshold Na+ spikes by pharmacological or electrophysiological means often revealed underlying small dendritic Ca2+ spikes. When cells displaying the low-threshold Na+ spikes were voltage clamped at membrane potentials that prevented firing of the soma or axon, corresponding tetrodotoxin-sensitive current spikes could be evoked all-or-none by dendritic depolarization. We conclude that these low-threshold Na+ spikes were initiated in the dendrite, probably by local Ca2+ spikes, and subsequently propagated actively to the soma. Most cells displaying dendritic Na+ spikes fired multiple bursts of action potentials during tonic dendritic depolarization, whereas somatic depolarization of the same cells evoked only regular firing. We discuss the implications of dendritic Ca2+ and Na+ spikes for synaptic integration and neural input-output relations.