Developmental Sensitivity of Hippocampal Interneurons to Ethanol: Involvement of the Hyperpolarization-Activated Current, Ih

Abstract

Ethanol (EtOH) has powerful effects on GABA(A) receptor-mediated neurotransmission, and we have previously shown that EtOH-induced enhancement of GABA(A) receptor-mediated synaptic transmission in the hippocampus is developmentally regulated. Because synaptic inhibition is determined in part by the firing properties of interneurons, we have investigated the mechanisms whereby EtOH influences the spontaneous firing characteristics and hyperpolarization-activated cation current (Ih) of hippocampal interneurons located in the near to the border of stratum lacunosum moleculare and s. radiatum of adolescent and adult rats. EtOH did not affect current injection-induced action potentials of interneurons that do not exhibit spontaneous firing. However, in neurons that fire spontaneously, EtOH enhanced the frequency of spontaneous action potentials (sAPs) in a concentration-dependent manner, an effect that was more pronounced in interneurons from adolescent rats, compared with adult rats. EtOH also modulated the afterhyperpolarization (AHP) that follows sAPs by shortening the tau(slow) decay time constant, and this effect was more pronounced in slices from adolescent rats. EtOH increased Ih amplitudes, accelerated Ih activation kinetics, and increased the maximal Ih conductance in interneurons from animals in both age groups. These effects were also more pronounced in interneurons from adolescents and persisted in the presence of glutamatergic and GABAergic blockers. However, EtOH failed to affect sAP firing in the presence of ZD7288 or cesium chloride. These results suggest that Ih may be of mechanistic significance in the effect of EtOH on interneuron spontaneous firing.