Quantitative analysis of synaptic potentiation during kindling of the perforant path

Abstract

Synaptic transmission was studied during the development of kindling in the pathway from entorhinal cortex (EC) to dentate gyrus (DG) of unrestrained unanesthetized rats using chronic neurophysiological techniques. Extracellular field potentials were recorded from the DG in response to activation of the perforant pathway with 0.1-ms constant current square-wave pulses. The evoked field potentials consisted of a population EPSP (a reflection of excitatory synaptic activation) and a population spike (a measure of synchronous postsynaptic discharge of granule cells). Synaptic efficacy was quantitated in this pathway by measurement of the population EPSP slope and population spike amplitude across a range of stimulus intensities from threshold to maximal evoked response. Input-output relationships for population EPSP and population spike were determined at regular intervals during the course of kindling, corresponding to the stages of evoked behavioral seizures. Increases in the population EPSP and population spike were observed after a single kindling stimulus that evoked afterdischarge (AD) when behavioral seizures were minimal. Evaluation of the input-output relationships for the group of kindled animals at the various stages of evoked behavioral seizure activity revealed that increases in the population EPSP continued to slowly evolve with repeated stimulations but that increases in the population spike were maximal after one or at most a few stimulations that evoked AD. The increases in both population EPSP and population spike persisted for the duration of the recording, i.e., through induction of generalized motor convulsions. To evaluate the translation of synaptic activation into cell discharge during kindling, we made use of the population spike/population EPSP ratio across a range of stimulus intensities. The spike/EPSP ratios revealed a dissociation of the population spike and population EPSP early in the course of kindling during class 1 seizures. Specifically, after induction of an AD, an extracellular population EPSP of a given size evoked a larger population spike than an EPSP of comparable size before the induction of an AD by kindling stimulation. The development of generalized motor convulsions (class 5 seizures) was associated with a reduction in the spike/EPSP ratio. The mechanism of this reduction in spike/EPSP ratio is uncertain, but since synaptic activation (as reflected by population EPSP) did not decline during class 5 seizures, the reduction in the spike/EPSP ratio could be consistent with increased inhibition after generalized motor convulsions, or could reflect a decrease in granule cell excitability.(ABSTRACT TRUNCATED AT 400 WORDS)