The Journal of Neurophysiology Vol. 79 No. 1 January 1998, pp. 106-116
Copyright ©1998 The American Physiological Society

Local Circuit Abnormalities in Chronically Epileptic Rats After Intrahippocampal Tetanus Toxin Injection in Infancy

Karen L. Smith¹, Chong L. Lee¹, and John W. Swann^{1, 2}

¹ The Cain Foundation Laboratories, Department of Pediatrics; and ² Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

Smith, Karen L. Chong L. Lee, and John W. Swann. Local circuit abnormalities in chronically epileptic rats after intrahippocampal tetanus toxin injection in infancy. J. Neurophysiol. 79: 106-116, 1998. 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 5-7 days. Hippocampal slices were then taken from these rats in adulthood because 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 (ACSF), 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 0.05-0.1 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 CA_3C 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 (2-8 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 CA_3C, 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. On blockade of -aminobutyric acid (GABA_A) receptors, slices from experimental rats underwent prolonged electrographic seizures that were up to 10 s in duration. In contrast, slices from control rats produced only brief 100-ms network bursts. These results suggest that a change in excitability within CA_3C 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 GABA_A-mediated synaptic inhibition.

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