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The Journal of Neuroscience, November 15, 2002, 22(22):9922-9931

Divergent GABA_A Receptor-Mediated Synaptic Transmission in Genetically Seizure-Prone and Seizure-Resistant Rats

Dan C. McIntyre¹, Bruce Hutcheon^{1, 2}, Kerstin Schwabe³, and Michael O. Poulter^{1, 2}

¹ Neuroscience Research Institute, Carleton University, Ottawa, Ontario, Canada K1S 5B6, ² Laboratory of Molecular Neuropharmacology, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6, and ³ Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, D-30559 Hannover, Germany

Recent evidence suggests that abnormal expression of GABA_A receptors may underlie epileptogenesis. We observed previously that rats selectively bred to be seizure-prone naturally overexpressed, as adults, GABA  subunits (2, 3, and 5) seen at birth, whereas those selected to be seizure-resistant overexpressed the adult, 1 subunit. In this experiment, we gathered GABA miniature IPSCs (mIPSCs) from these strains and correlated their attributes with the subunit expression profile of each strain compared with a normal control strain. The mIPSCs were collected from both cortical pyramidal and nonpyramidal neurons. In seizure-prone rats, mIPSCs were smaller and decayed more slowly than in normal rats, which in turn were smaller and slower than in seizure-resistant rats. A detailed analysis of individual mIPSCs revealed two kinds of postsynaptic responses (those with monoexponential vs biexponential decay) that were differentially altered in the three strains. The properties of monoexponentially decaying mIPSCs did not differ between pyramidal and nonpyramidal neurons within a strain but differed between strains. In contrast, an interaction was observed between cell morphology and strain for biexponentially decaying mIPSCs. Here, the mIPSCs of pyramidal neurons in the seizure-resistant rats formed a distinct subpopulation compared with the seizure-prone rats; yet in the latter rats, it was the mIPSCs of the nonpyramidal neurons that were unique. Given these differences, we were surprised to find that the total inhibitory charge transfer between the strains was similar. This suggests that the timing of inhibition, particularly slow inhibitory neurotransmission between nonpyramidal neurons, may be a contributing factor in seizure genesis.

Key words: subunits; epilepsy; GABA_A receptors; inhibitory currents; interneurons; perirhinal cortex

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22229922-10$05.00/0

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