Differential expression of voltage-gated K + currents in medial septum/diagonal band complex neurons exhibiting distinct firing phenotypes

Abstract

The medial septum/diagonal band complex (MSDB) controls hippocampal excitability, rhythms and plastic processes. Medial septal neuronal populations display heterogeneous firing patterns. In addition, some of these populations degenerate during age-related disorders ( e.g. cholinergic neurons). Thus, it is particularly important to examine the intrinsic properties of theses neurons in order to create new agents that effectively modulate hippocampal excitability and enhance memory processes. Here, we have examined the properties of voltage-gated, K + currents in electrophysiologically-identified neurons. These neurons were taken from young rat brain slices containing the MS/DB complex. Whole-cell, patch recordings of outward currents were obtained from slow firing, fast-spiking, regular-firing and burst-firing neurons. Slow firing neurons showed depolarization-activated K + current peaks and densities larger than in other neuronal subtypes. Slow firing total current exhibited an inactivating A-type current component that activates at subthreshold depolarization and was reliably blocked by high concentrations of 4-AP. In addition, slow firing neurons expressed a low-threshold delayed rectifier K + current component with slow inactivation and intermediate sensitivity to tetraethylammonium. Fast-spiking neurons exhibited the smaller I K and I A current densities. Burst and regular firing neurons displayed an intermediate firing phenotype with I K and I A current densities that were larger than the ones observed in fast-spiking neurons but smaller than the ones observed in slow-firing neurons. In addition, the prevalence of each current differed among electrophysiological groups with slow firing and regular firing neurons expressing mostly I A and fast spiking and bursting neurons exhibiting mostly delayer rectifier K + currents with only minimal contributions of the I A. The pharmacological or genetic modulations of these currents constitute an important target for the treatment of age-related disorders.