Abstracts

RATIONALE: Despite numerous studies describing the antiepileptic efficacy of ketogenic diet (KD) treatment, mechanisms underlying anticonvulsant effects of the KD remain to be elucidated. The present study was designed to characterize electrophysiologically the synaptic excitability of hippocampal pyramidal cells in slices from KD-fed rats. METHODS: Sprague-Dawley rats were maintained on either KD or a calorie-matched normal diet treatment starting at P37. At P66-68, animals were sacrificed and hippocampal slices were prepared. Slices were maintained in normal ACSF (including 10 mM glucose, 0 mM b-hydroxybutyrate) at room temperature for at least 1 hr prior to being transferred to an interface chamber where they were perfused with carbogenated ACSF at 33-35 degrees C. Field potential recordings were obtained from the CA1 pyramidal cell layer in response to stimulation of the Schaffer collaterals. Input/output (I/O) curves and paired-pulse relationships were calculated for the population spike. RESULTS: Ketogenic animals exhibited a significantly slower rise to plateau for I/O curves as compared to controls. There was no difference in the maximal level of response between diet groups. Although paired-pulse analysis did not yield any significant differences between KD- and control-fed animals, there was a consistent tendency for greater population spike enhancement in slices from KD animals at all interpulse intervals tested (20-750ms). CONCLUSIONS: These preliminary findings suggest that there are differences in synaptic excitability between KD- and control-fed animals. Such differences appear to be maintained in hippocampal slices, even though tissue from both groups was maintained in normal ACSF -- with glucose, but without b-hydroxybutyrate. Future studies will be required to corroborate these initial observations. Supported by NIH NS 18995 and 07144, and the UW Pediatric Epilepsy Research Center (PERC).