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This Article Full Text Full Text (PDF) All Versions of this Article: 101/1/67    most recent 90557.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yan, H. Articles by Swartzwelder, H. S. Search for Related Content PubMed PubMed Citation Articles by Yan, H. Articles by Swartzwelder, H. S.

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

¹Departments of Psychiatry, ²Pharmacology, ⁵Surgery, and ⁶Neurobiology, Duke University Medical Center, Durham; ³Neurobiology Research Laboratory, Veterans Affairs Medical Center, Durham; and ⁴Research Service of the Veterans Affairs Medical Center, Durham, North Carolina

Submitted 13 May 2008; accepted in final form 21 October 2008

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 (I_h) 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 _slow decay time constant, and this effect was more pronounced in slices from adolescent rats. EtOH increased I_h amplitudes, accelerated I_h activation kinetics, and increased the maximal I_h 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 I_h may be of mechanistic significance in the effect of EtOH on interneuron spontaneous firing.

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