title: Divergent GABA(A) receptor-mediated synaptic transmission in genetically seizure-prone and seizure-resistant rats.
abstract: 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 alpha subunits (alpha2, alpha3, and alpha5) seen at birth, whereas those selected to be seizure-resistant overexpressed the adult, alpha1 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.
authors.affiliation: Neuroscience Research Institute, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
authors.forename: Dan C
authors.initials: DC
authors.lastname: McIntyre
authors.forename: Bruce
authors.initials: B
authors.lastname: Hutcheon
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schwabe
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology; D020534:Parahippocampal Gyrus / Q000166:cytology / Q000502:physiology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010641:Phenotype; D017966:Pyramidal Cells / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D012016:Reference Values; D012640:Seizures / Q000235:genetics / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D011963:Receptors, GABA-A