AXON Terminal Hyperexcitability Seen in Epileptogenesis In Vitro

Abstract

In the study of epilepsy, a great deal of attention has been devoted to synaptic mechanisms of seizure induction and expression. Many efforts have focused on understanding changes in the balance between synpatic excitation and inhibition. For example, the application of a number of excitatory amino acids can evoke epileptiform activity (Lehman et al., 1987; McCaslin and Morgan, 1986;. Meldrum, 1986; Piredda and Gale, 1986; Turski et al., 1987a,b), and, conversely, antagonists of excitatory amino acid receptors can suppress seizures or seizurelike activity in some models (Czuczwar et al., 1985; Czuczwar and Meldrum, 1982; De Sarro et al., 1985; Heinemann et al., 1985; Lehman et al., 1987; McNamara et al., 1988; Meldrum, 1986; Sagratella et al., 1987; Traynelis and Dingledine, 1988; Turski et al., 1987a; Walther et al., 1986). Changes in responses to excitatory amino acids are associated with pathological neuroplasticity and accompany both in vivo kindling and similar in vitro stimulation models of epileptogenesis (Mody et al., 1988; Stelzer et al., ss1987). In addition to altering the receptor mediation of synaptic responses, excitation within a neural network may be increased by altering the frequency and probability of synaptic transmission. Thus, in the hippocampal slice, the application of convulsant drugs, disturbances in extracellular ion concentrations, and tetanic stimulation which leads to epileptiform activity can all result in a greater number of excitatory synaptic interactions between cells.