The Journal of Neurophysiology Vol. 78 No. 5 November 1997, pp. 2804-2810
Copyright ©1997 The American Physiological Society

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Epileptogenesis Following Neocortical Trauma From Two Sources of Disinhibition

Lie Yang and Larry S. Benardo

Departments of Pharmacology and Neurology, State University of New York, Health Science Center, Brooklyn, New York 11203

Yang, Lie and Larry S. Benardo. Epileptogenesis following neocortical trauma from two sources of disinhibition. J. Neurophysiol. 78: 2804-2810, 1997. Intracellular and field potential recordings were obtained from superficial and deep neurons from both intact coronal rat somatosensory slices, and from slices which had been acutely divided into a superficial strip of cortex (~450 µm from the pia) and a deep segment. Membrane properties for cells in the traumatized slices were similar to those of their counterparts in intact slices. However, synaptic hyperexcitability developed in the deep segments in which a majority of cells likely underwent dendrotomy. This hyperexcitability was manifested by epileptiform activity in 54% of traumatized slices. Measurements of fastGABAergic inhibitory strength showed these slices were disinhibited. Superficial delivery of tetrodotoxin to the upper 450 µm of intact slices led to disinhibition of fast GABAergic transmission as well as an attendant increase in excitatory postsynaptic potential strength but not epileptogenesis. Pharmacological maneuvers aimed at preventing glutamate-triggered increases in intracellular calcium [glutamate ionotropic antagonists, dantrolene, and bis-(o-aminophenoxy)-N,N,N,N-tetraacetic acid (BAPTA)-AM] showed that a 1 h treatment in these agents conferred protection against epileptogenesis. These results demonstrate that the seizure-like activity developing in deep dendrotomized cortical segments resulted from two sources of GABAergic disinhibition: the physical removal of important superficial inhibitory circuits and glutamate-triggered increases in intracellular calcium.

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