Medial septal/diagonal band cells express multiple functional nicotinic receptor subtypes that are correlated with firing frequency

Abstract

The medial septum-diagonal band (MS/DB) contains primarily cholinergic and GABAergic neurons that project to the hippocampus, and are important for learning and memory. Whole-cell patch clamp methods with brain slices from p11–p20 rats were used to measure MS/DB cell responses to focal somatic application of 1 mM acetylcholine (ACh) and a series of current pulses was applied in order to assess firing frequencies and the presence of hyperpolarization-activated currents (Ih). We identified three types of cells: (1) cells with fast inward currents blocked by methyllycaconitine (MLA) with slow firing rates (3–12 Hz), accommodating action potentials, and no Ih ( n = 20); (2) cells with currents that had both fast (MLA-sensitive) and slow components that were blocked with mecamylamine (MEC) that showed fast firing (up to 60 Hz) and slow firing (up to 3 Hz), with accommodating and non-accommodating action potentials ( n = 46), 33% of which had Ih; and (3) cells not responsive to ACh with moderate firing rates (10–42 Hz), some with accommodating action potentials and some without ( n = 19), of which 92% had Ih. These results are among the first to demonstrate functional nicotinic receptors in the MS/DB. The data suggest that these receptors include α7 and non-α7 subtypes and that the expression of each is correlated with firing frequency and the presence of Ih. Responses to ACh were not affected by tetrodotoxin (TTX) and CdCl 2 but were blocked by MLA or MLA and MEC, suggesting that these currents involve direct activation of nicotinic receptors.