Abstracts

Some Mongolian gerbils ([italic]Meriones unguiculatus)[/italic] develop epilepsy 1-2 months after birth, but mechanisms are unknown. Seizures in these gerbils can be elicited by exposure to novel environments, providing control of seizure onset in an epilepsy model arising during natural development, rather than from injury or disease. It has been proposed that excessive inhibition of dentate interneurons could [ldquo]disinhibit[rdquo] dentate granule cells, thus predisposing these gerbils to seizures. To test this, we recorded from multiple, single neurons in dentate gyrus before and during seizures evoked by exposure to novel environments. If the hypothesis were correct, then action potential frequency would be expected to decrease in interneurons and increase in granule cells before seizure onset., Multiple, single neurons were recorded using tetrodes from the granule cell layer of dentate gyrus in 3, awake, freely-moving, adult gerbils. Recordings were obtained for 20 min ([ldquo]baseline[rdquo] interictal period), while gerbils rested in their home cage. Seizures (N=1, 1 and 3, resp.) were initiated by moving gerbils from their home cage to a metal table top, which normally elicited a seizure within 1 min ([ldquo]preictal[rdquo] period). Seizures consisted of tonic-clonic convulsions. Seizure onset was identified offline as the earliest of five electrographic measures. Action potentials from individual neurons were identified by grouping ([ldquo]cluster cutting[rdquo]) similar waveform parameters (e.g., peak amplitude) from data obtained during the baseline period. Neurons were classified as those with low firing rate ([lt] 5 Hz) and broad spikewidth ([gt] 250 [mu]sec) that fired in bursts (putative granule cells; N=9) or those with high firing rate ([gt] 5 Hz) and narrow spikewidth ([lt] 250 [mu]sec) that were tonically active (putative interneurons; N=7). Action potential frequencies were plotted relative to seizure onset, binned (bin width = 10 sec) and compared to baseline levels using a repeated-measures ANOVA (p=0.05)., No significant differences were observed between baseline and preictal action potential frequency in granule cells (2.7 [plusmn] 0.7 Hz baseline vs. 2.7 [plusmn] 1.0 Hz preictal, ANOVA, p=0.958) or interneurons (10.6 [plusmn] 2.5 Hz vs. 11.9 [plusmn] 2.1 Hz, p=0.665)., The lack of significant changes in action potential frequency in either granule cells or interneurons during the preictal period suggests that seizures in Mongolian gerbils are not initiated by disinhibition in dentate gyrus. These preliminary results do not reject the possibility that disinhibition plays a role in seizure initiation in other brain structures. They do, however, show the utility of recording multiple, single neurons in vivo for testing hypotheses of ictal transition by identifying activity changes in specific neuron classes with respect to spontaneous seizure onset., (Supported by NIH/NINDS and the Eric W. Lothman fellowship from the Epilepsy Foundation.)