Voltage-Gated Sodium Channels Shape Subthreshold EPSPs in Layer 5 Pyramidal Neurons From Rat Prefrontal Cortex

Abstract

The role of voltage-dependent channels in shaping subthreshold excitatory postsynaptic potentials (EPSPs) in neocortical layer 5 pyramidal neurons from rat medial prefrontal cortex (PFC) was investigated using patch-clamp recordings from visually identified neurons in brain slices. Small-amplitude EPSPs evoked by stimulation of superficial layers were not affected by the N-methyl-d-aspartate receptor antagonistd-2-amino-5-phosphonopentanoic acid but were abolished by the AMPA receptor antagonist 6-cyano-7-nitroquinoxalene-2,3-dione, suggesting that they were primarily mediated by AMPA receptors. AMPA receptor-mediated EPSPs (AMPA-EPSPs) evoked in the apical dendrites were markedly enhanced, or increased in peak and duration, at depolarized holding potentials. Enhancement of AMPA-EPSPs was reduced by loading the cells with lidocaine N-ethylbromide (QX-314) and by local application of the Na+ channel blocker tetrodotoxin (TTX) to the soma but not to the middle/proximal apical dendrite. In contrast, blockade of Ca2+ channels by co-application of Cd2+ and Ni2+ to the soma or apical dendrite did not affect the AMPA-EPSPs. Like single EPSPs, EPSP trains were shaped by Na+ but not Ca2+ channels. EPSPs simulated by injecting synaptic-like current into proximal/middle apical dendrite (simEPSPs) were enhanced at depolarized holding potentials similarly to AMPA-EPSPs. Extensive blockade of Ca2+ channels by bath application of the Cd2+ and Ni2+ mixture had no effects on simEPSPs, whereas bath-applied TTX removed the depolarization-dependent EPSP amplification. Inhibition of K+ currents by 4-aminopyridine (4-AP) and TEA increased the TTX-sensitive EPSP amplification. Moreover, strong inhibition of K+ currents by high concentrations of 4-AP and TEA revealed a contribution of Ca2+channels to EPSPs that, however, seemed to be dependent on Na+ channel activation. Our results indicate that in layer 5 pyramidal neurons from PFC, Na+, and K+ voltage-gated channels shape EPSPs within the voltage range that is subthreshold for somatic action potentials.