Neurons dissociated from the hippocampal formations of neonatal rats were grown in medium containing kynurenic acid (a glutamate receptor antagonist) and elevated Mg*+. Such chronically blocked neurons, when first exposed to medium without blockers (after 0.5-5.0 months), generated intense seizure-like activity. This consisted of bursts of synchronous electrical responses that resembled paroxysmal depolarization shifts and sustained depolarizations that, in some neurons, nearly abolished the resting potential. Sustained depolarizations were usually reversed by timely application of kynurenate or Z-amino-5-phosphonovalerate, indicating that continuous activation of glutamate receptors was required for their maintenance. Prolonged periods of intense seizure-like activity usually killed most neurons in the culture. This system allows seizurerelated cellular mechanisms to be studied in long-term cell culture. introduction

The characteristic feature of seizure activity is an abnormal synchronization of electrical events in a population of neurons(Dichter and Ayala, 1987). Such synchronization can occur ifthe circuitry permits sufficient recurrent excitation, especially if synaptic inhibition is reduced (Traub et al., 1987); a number of other factors contribute to the generation of seizure events (Dichter and Ayala, 1987). To induce such activity for experimental study, intact brains or cortical slices have been exposed to a varrrty of treatments-commonly, agents that block synaptic inhibition(Kandel and Spencer, 1961; Matsumoto and Ajmone-Marsan, 1964a, 196413; Dichter and Spencer, 1969: reviewed by Dichter and Ayala, 1987). We report here a model system for studying seizure-like activity in hippocampal neurons in dissociated-cell culture. The seizure-prone behavior was induced by long-term exposure of the neurons to agents that attenuate synap-UC transmission.