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Long-Term Modulation of A-Type K+ Conductances in Hippocampal CA1 Interneurons in Rats After Chronic Intermittent Ethanol Exposure During Adolescence or Adulthood

Authors

  • Qiang Li,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
    3. Department of Neurosugery , Duke University Medical Center, Durham, North Carolina
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  • Rebekah L. Fleming,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
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  • Shawn K. Acheson,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
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  • Roger D. Madison,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Neurosugery , Duke University Medical Center, Durham, North Carolina
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  • Scott D. Moore,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
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  • Mary-Louise Risher,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
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  • Wilkie A. Wilson,

    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Social Sciences Research Institute, Duke University, Durham, North Carolina
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  • H. Scott Swartzwelder

    Corresponding author
    1. Durham VA Medical Center , Duke University Medical Center, Durham, North Carolina
    2. Department of Psychiatry , Duke University Medical Center, Durham, North Carolina
    • Reprint requests: Dr. H. Scott Swartzwelder, Department of Psychiatry, Duke University Medical Center and Durham VA Medical Center, Room 24, Building 16, VAMC, 508 Fulton Street, Durham, NC 27705; Tel.: 919-971-0964; Fax: 919-286-6811; E-mail: hss@duke.edu

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Abstract

Background

Chronic alcohol use, especially exposure to alcohol during adolescence or young adulthood, is closely associated with cognitive deficits that may persist into adulthood. Therefore, it is essential to identify possible neuronal mechanisms underlying the observed deficits in learning and memory. Hippocampal interneurons play a pivotal role in regulating hippocampus-dependent learning and memory by exerting strong inhibition on excitatory pyramidal cells. The function of these interneurons is regulated not only by synaptic inputs from other types of neurons but is also precisely governed by their own intrinsic membrane ionic conductances. The voltage-gated A-type potassium current (IA) regulates the intrinsic membrane properties of neurons, and disruption of IA is responsible for many neuropathological processes including learning and memory deficits. Thus, it represents a previously unexplored cellular mechanism whereby chronic ethanol (EtOH) may alter hippocampal memory-related functioning.

Methods

Using whole-cell electrophysiological recording methods, we investigated the enduring effects of chronic intermittent ethanol (CIE) exposure during adolescence or adulthood on IA in rat CA1 interneurons.

Results

We found that the mean peak amplitude of IA was significantly reduced after CIE in either adolescence or adulthood, but IA density was attenuated after CIE in adolescence but not after CIE in adulthood. In addition, the voltage-dependent steady-state activation and inactivation of IA were altered in interneurons after CIE.

Conclusions

These findings suggest that CIE can cause long-term changes in IA channels in interneurons and thus may alter their inhibitory influences on memory-related local hippocampal circuits, which could be, in turn, responsible for learning and memory impairments observed after chronic EtOH exposure.

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