Convulsant and Anticonvulsant Effects on Spontaneous CA3 Population Bursts

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Abstract
This paper analyzes the effects of a convulsant and an anticonvulsant manipulation on spontaneous bursts in CA3 pyramidal cells in the in vitro slice preparation under conditions of low (3.3 mM [K+]o) and high (8.5 mM [K+]o) burst probability. When burst probability was low, the anticonvulsant, pentobarbital, produced the anticipated effects: the burst duration decreased and interburst interval increased. However, when burst probability was high, both anticonvulsant and convulsant manipulations decreased the interburst interval and the burst duration. To reconcile these findings, we utilized a model in which CA3 burst duration is limited by activity-dependent depression of CA3 excitatory recurrent collateral synapses and the interburst interval is determined by the time required to recover from this depression. We defined the burst end threshold as the level of synaptic depression at which bursts terminate, and the burst start threshold as the level of synaptic depression at which burst initiation is possible. Synapses were considered to oscillate between these thresholds. When average burst duration and interburst interval data were fit using this model, the paradoxically similar effects of the convulsant and anticonvulsant manipulations could be quantitatively interpreted. The convulsant maneuver decreased both the burst start and end thresholds. The start threshold decreased more than the end threshold, so that the thresholds were closer together. This decreased the time needed to transition from one threshold to the other, i.e., the interburst interval and burst duration. The anticonvulsant manipulation primarily increased the burst end threshold. This also decreased the difference between thresholds, decreasing both interburst interval and burst duration. This model resolves the paradoxical proconvulsant effects of pentobarbital in the CA3 preparation and provides insights into the effects of anticonvulsants on epileptiform discharges in the human EEG.