Abstract
Ethanol (EtOH) promotes GABAergic synaptic transmission in the central nervous system. We have shown that EtOH enhances the frequency of GABAA receptor-mediated spontaneous inhibitory postsynaptic currents less powerfully in hippocampal CA1 pyramidal neurons from adolescent animals compared with those from adults. However, we have also shown that EtOH promotes the firing of hippocampal interneurons, located in stratum lacunosum moleculare (SLM), from adolescent animals more potently than in those from adults. Thus the latter finding would seem to be inconsistent with the former. To understand this apparent inconsistency, we have now assessed the effects of EtOH on a different subpopulation of hippocampal interneurons, those with somata located in the stratum oriens (SO). We found that EtOH-induced enhancement of the frequency of spontaneous action potentials (sAPs) was less in interneurons from adolescent rats compared with those from adults. In addition, EtOH-induced reduction of the afterhyperpolarization decay time constant (τslow) was less pronounced in interneurons from adolescent rats, as was the EtOH-induced increase in the amplitude of the hyperpolarization-activated cation current, Ih. The effect of EtOH on sAP firing frequency was blocked by application of the Ih antagonist 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride (ZD7288). These results indicate that although EtOH promotes the firing of hippocampal interneurons, through promotion of Ih, the developmental expression of this effect differs between interneurons with somata located in the SO and SLM.
Footnotes
This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA01489] (to H.S.S.), Merit Review grants and Senior Research Career Scientist awards from the U.S. Department of Veterans Affairs (to H.S.S. and W.A.W.), and an Institute for Medical Research, Inc. award (to H.Y.).
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.168450.
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ABBREVIATIONS:
- EtOH
- ethanol
- SLM
- stratum lacunosum moleculare
- SO
- stratum oriens
- sAP
- spontaneous action potential
- AHP
- afterhyperpolarization
- Ih
- hyperpolarization-activated cation current
- τslow
- slow decay time constant
- PD
- postnatal day
- IPSC
- inhibitory postsynaptic current
- ZD7288
- 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride
- TTX
- tetrodotoxin
- ANOVA
- analysis of variance
- aCSF
- artificial cerebrospinal fluid.
- Received March 24, 2010.
- Accepted July 20, 2010.
- U.S. Government work not protected by U.S. copyright
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