Evidence for a chronic loss of inhibition in the hippocampus after kindling: biochemical studies.
Brain tissue from kindled animals prepared 1 month after their last seizure was compared to tissue from matched surgical control animals. Quantitative film autoradiography was used to study muscimol binding in the CA1 region and 3 other brain areas (dentate gyrus, cerebral cortex, and thalamus). The Kd values so obtained were constant from region to region and comparable to those published by others. Bmax values varied; of the 4 regions studied CA1 had the lowest value of Bmax. There were no differences in either Kd or Bmax values in any region studied between kindled and surgical control rats. The release of GABA from nerve terminals was assessed with hippocampal tissue maintained in vitro and perfused with different solutions in which the concentrations of K+ and Ca2+ were varied. This allowed the examination of K+-induced depolarization release and the Ca2+ dependence of this process. K+-induced, Ca2+-dependent release of GABA from hippocampus derived from kindled animals was significantly less than that from hippocampus derived from controls. The biochemical studies reported here provide additional support for the hypothesis that there is a chronic decrease in GABA-mediated inhibition in the hippocampus associated with kindling. The data point to a dysfunction at the presynaptic level, within the GABAergic interneuron, but do not exclude changes at a level postsynaptic to the GABAergic interneuron not detected with the methods employed.
Kapur
J
J
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908.
Bennett
J P
JP
Wooten
G F
GF
Lothman
E W
EW
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007696:Kindling, Neurologic; D008297:Male; D009118:Muscimol / Q000378:metabolism*; D009433:Neural Inhibition; D051381:Rats; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D009118:Muscimol; D005680:gamma-Aminobutyric Acid