Sustained hyperexcitability elicited by repetitive electric stimulation of organotypic hippocampal explants

Abstract

Sustained or complex evoked extracellular slow-wave field potentials were recorded in the CA3/2 areas of organotypic hippocampal explants following stimulation of the dentate area. After repetitive electric stimulation, these discharges became more complex and/or self-sustaining. Self-sustaining discharges continued to occur for the duration of the experiment (15 min-10 h). These slow-wave discharges were evoked (or occurred spontaneously) over a wide range of extracellular K+ concentrations (3-9 mM) without addition of pharmacologic inhibitory antagonists, whereas in some explants raising extracellular K+ from 5.9 to 8-9 mM resulted in spontaneous discharges. The observation that epileptiform discharges in hippocampal explants often occurred spontaneously, were elicited by repetitive electric stimulation, and were recorded at K+ levels which are generally ineffective in acute adult hippocampal slices, indicates that excitability of these CNS explants may be significantly increased following altered neuronal and synaptic development (and/or reorganization) under isolated conditions in culture.