ENDOGENOUS BURSTS UNDERLIE SEIZURELIKE ACTIVITY IN SOLITARY EXCITATORY HIPPOCAMPAL-NEURONS IN MICROCULTURES

1. I compared the relative contributions of synaptic potentials and en dogenous bursting to seizurelike activity in a simple model system. Th e system consisted ofa solitary excitatory hippocampal rat neuron in a microculture. Each solitary excitatory neuron was grown in kynurenate and elevated magnesium and had excitatory autapses. 2. In normal phys iological solution most neurons displayed the characteristic type of i nterictal epileptiform activity, the paroxysmal depolarizing shift (PD S). A minority of neurons displayed ictuslike epileptiform activity co nsisting of runs of PDSs with a sustained neuronal depolarization. 3. I analzyed the synaptic and nonsynaptic components underlying these fo rms of epileptiform activity. The synaptic and calcium current compone nts of the epileptiform activity were removed by using a ''synapse blo cking solution'' in which calcium was replaced with magnesium, and glu tamate receptor activity was blocked using the glutamate antagonists 2 -amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. N eurons that had only PDSs in normal physiological solution typically d isplayed only one or two action potentials in this synapse blocking so lution. In contrast, neurons that had sustained depolarizations in nor mal physiological solution generally displayed bursts of action potent ials in the synapse blocking solution, and some of the bursts had plat eau depolarizations that lasted as long as several seconds. 4. The sec onds-long endogenous plateau depolarizations were suppressed by tetrod otoxin, indicating involvement of persistent sodium currents. 5. The p lateau depolarizations were shortened or abolished by 8 mu M phenytoin , but there was only a small effect of phenytoin on nonplateau sustain ed repetitive firing of action potentials. 6. Elevation of extracellul ar potassium to 8 mM typically intensified the endogenous activity, us ually converting action potential bursts to bursts with plateaus. 7. T his study demonstrates that a sodium-dependent endogenous bursting und erlies ictuslike epileptiform activity in this model system of seizure like activity. The ability of phenytoin to attenuate this endogenous b ursting suggests that a similar mechanism might underlie epileptiform bursting in less reduced systems such as brain slices or intact animal s.