LOCAL CIRCUIT ABNORMALITIES IN CHRONICALLY EPILEPTIC RATS FOLLOWING INTRAHIPPOCAMPAL TETANUS TOXIN INJECTION IN INFANCYT. Karen L. Smith, Chong L. Lee, John W. Swann. The Cain Foundation Laboratories, Department of Pediatrics, and Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.
APStracts 4:261N, 1997.
ABSTRACT
In vitro slice experiments were undertaken in adult rats to investigate the physiological origins of a chronic epileptic condition that was initiated in infancy. A unilateral injection of a minute quantity of tetanus toxin into hippocampus on postnatal day 10 produced a severe convulsive syndrome characterized by brief but repeated seizures that lasted for 5 to 7 days. Hippocampal slices were then taken from these rats in adulthood since at this time previous studies have shown the occurrence of electrographic and behavioral seizures. Dramatic alterations in local circuit functioning were observed. In normal artificial cerebrospinal fluid, spontaneous epileptiform network bursts were recorded in a majority (73%) of experimental rats. Network bursts occurred in area CA3 of both the injected and contralateral hippocampus. These consisted of intracellular depolarization shifts that were coincident with extracellularly recorded network bursts. Often they occurred at frequencies of 0.05 to 0.1 Hz and although variable in amplitude and duration, had all-or-none_like qualities. These events appeared to arise largely from local circuits in the CA3C subfield. Network bursts were rarely recorded in area CA1 and were never observed in the dentate gyrus. However, in 31% of rats, a novel, higher frequency (2 to 8 Hz) field potential was recorded in area CA1. This was coincident with rhythmic intracellularly recorded inhibitory postsynaptic potentials (ipsps). These summated ipsps blocked action potential firing and reversed polarity near -75 mV. To understand the origins of network bursting in area CA3C, comparisons were made of the fundamental neurophysiological properties of pyramidal cells in epileptic and control rats. Of the passive and active membrane properties examined, all appeared normal. Unusually prolonged bursts of action potentials were observed in a small subset of pyramidal cells. However, on average the duration of intrinsic bursts were unaltered in the CA3 neurons analyzed from experimental rats. To explore the role that alterations in CA3 recurrent excitatory network excitability may play in epileptiform discharges, picrotoxin was bath applied. Upon blockade of GABAA receptors, slices from experimental rats underwent prolonged electrographic seizures that were up to 10 seconds in duration. In contrast, slices from control rats produced only brief 100-millisecond network bursts. These results suggest that a change in excitability within CA3C recurrent excitatory networks likely contributes to seizures in chronically epileptic rats. However, at the same time, this hyperexcitability is controlled to an important degree by functional GABAA- mediated synaptic inhibition. 

Received 19 May 1997; accepted in final form 18 September 1997.
APS Manuscript Number J414-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997