Endogenous bursts underlie seizurelike activity in solitary excitatory hippocampal neurons in microcultures

1. I compared the relative contributions of synaptic potentials and endogenous bursting to seizurelike activity in a simple model system. The system consisted of a 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 physiological solution most neurons displayed the characteristic type of interictal epileptiform activity, the paroxysmal depolarizing shift (PDS). A minority of neurons displayed ictuslike epileptiform activity consisting of runs of PDSs with a sustained neuronal depolarization. 3. I analyzed the synaptic and nonsynaptic components underlying these forms of epileptiform activity. The synaptic and calcium current components of the epileptiform activity were removed by using a "synapse blocking solution" in which calcium was replaced with magnesium, and glutamate receptor activity was blocked using the glutamate antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. Neurons that had only PDSs in normal physiological solution typically displayed only one or two action potentials in this synapse blocking solution. In contrast, neurons that had sustained depolarizations in normal physiological solution generally displayed bursts of action potentials in the synapse blocking solution, and some of the bursts had plateau depolarizations that lasted as long as several seconds. 4. The seconds-long endogenous plateau depolarizations were suppressed by tetrodotoxin, indicating involvement of persistent sodium currents. 5. The plateau depolarizations were shortened or abolished by 8 microM phenytoin, but there was only a small effect of phenytoin on nonplateau sustained repetitive firing of action potentials. 6. Elevation of extracellular potassium to 8 mM typically intensified the endogenous activity, usually converting action potential bursts to bursts with plateaus. 7. This study demonstrates that a sodium-dependent endogenous bursting underlies ictuslike epileptiform activity in this model system of seizurelike activity. The ability of phenytoin to attenuate this endogenous bursting suggests that a similar mechanism might underlie epileptiform bursting in less reduced systems such as brain slices or intact animals.