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J. Neurosci. 24 (39): 8629-8639

Copyright © 2004 by the Society for Neuroscience.

Neurobiology of Disease

Altered Expression of the {delta} Subunit of the GABAA Receptor in a Mouse Model of Temporal Lobe Epilepsy

Zechun Peng,1 Christine S. Huang,1,4 Brandon M. Stell,2 Istvan Mody,2,3 , and Carolyn R. Houser1,3,4

Departments of 1Neurobiology, 2Neurology and Physiology, and 3Brain Research Institute, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, and 4Research Service, Veterans Administration Greater Los Angeles Healthcare System, West Los Angeles, Los Angeles, California 90073

Abstract: {delta} Subunit-containing GABAA receptors are located predominantly at nonsynaptic sites in the dentate gyrus where they may play important roles in controlling neuronal excitability through tonic inhibition and responses to GABA spillover. Immunohistochemical methods were used to determine whether {delta} subunit expression was altered after pilocarpine-induced status epilepticus in C57BL/6 mice in ways that could increase excitability of the dentate gyrus. In pilocarpine-treated animals, the normal diffuse labeling of the {delta} subunit in the dentate molecular layer was decreased by 4 d after status epilepticus (latent period) and remained low throughout the period of chronic seizures. In contrast, diffuse labeling of {alpha}4 and {gamma}2 subunits, potentially interrelated GABAA receptor subunits, was increased during the chronic period. Interestingly, {delta} subunit labeling of many interneurons progressively increased after pilocarpine treatment. Consistent with the observed changes in {delta} subunit labeling, physiological studies revealed increased excitability in the dentate gyrus of slices obtained from the pilocarpine-treated mice and demonstrated that physiological concentrations of the neurosteroid tetrahydrodeoxycorticosterone were less effective in reducing excitability in the pilocarpine-treated animals than in controls. The findings support the idea that alterations in nonsynaptic {delta} subunit-containing GABAA receptors in both principal cells and interneurons could contribute to increased seizure susceptibility in the hippocampal formation in a temporal lobe epilepsy model.

Key Words: tonic inhibitionneurosteroidsdentate gyrushippocampuspilocarpineimmunohistochemistry

Received for publication July 16, 2004. Revision received August 17, 2004. Accepted for publication August 18, 2004.

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