Abstracts

In temporal lobe epilepsy seizures initiate in mesial temporal lobe structures including dentate gyrus. Basket cells are important GABAergic interneurons in dentate gyrus. It has been proposed that: (1) During epileptogenic injuries neurons that provide excitatory synaptic input to basket cells are killed and basket cells become dormant, and (2) After granule cell axon sprouting excitatory synaptic input to basket cells is restored. If so, spontaneous EPSCs (sEPSCs) frequency in basket cells would be expected to decrease shortly after epileptogenic injuries and increase toward control values as granule cell axons sprout. To test this hypothesis we recorded sEPSCs in basket cells of control rats, pre-epileptic rats (3-7 d after pilocarpine-induced status epilepticus), and epileptic rats (17-41 d after status epilepticus)., 300 [mu]m-thick horizontal slices were prepared from male Sprague-Dawley rats. K-gluconate pipette solution was used for whole-cell patch clamp recordings. sEPSCs were recorded at -60 mV for 2 min (32[ordm]C). Recorded cells were identified by biocytin-labelling., Recordings were obtained from pyramidal-shaped interneurons at the border of granule cell layer and hilus. Two types of interneurons were found: regular-spiking interneurons and basket cells. Basket cells displayed higher firing frequency (140 [plusmn] 5 Hz at 600 pA current injection, n=7) than regular-spiking interneurons (96 [plusmn] 9 Hz, n=19, P[lt]0.001, t test). Action potentials were briefer in basket cells (0.70 [plusmn] 0.02 ms, n=8) than regular-spiking interneurons (1.42 [plusmn] 0.06 ms, n=45, P[lt]0.001). And basket cells had numerous axons concentrated in granule cell layer, while regular-spiking interneurons projected axons to molecular layer. sEPSC data were obtained only from electrophysiologically and morphologically identified basket cells. In controls, basket cell sEPSC frequency was 49 [plusmn] 15 Hz (n=5). In pre-epileptic and epileptic rats, sEPSC frequency was reduced to 73% (n=5, P=0.35) and 69% (n=6, P=0.32) of controls. Charge transfer per time of sEPSCs in basket cells was 6 [plusmn] 3 pA in controls. In pre-epileptic and epileptic rats, it was reduced to 41% (P=0.23) and 56% (P=0.35) of controls., These preliminary findings are consistent with the hypothesis that excitatory synaptic input to basket cells decreases after epileptogenic injuries but do not support the hypothesis that excitatory synaptic input is restored as granule cell axons sprout. Potential sources of lost excitatory synaptic input to basket cells include CA3 pyramidal cells, mossy cells, and layer II neurons in entorhinal cortex. Additional mechanisms include decreased activity of presynaptic neurons and decreased release probability of excitatory synapses. Overall, these findings suggest that basket cells may receive less excitatory synaptic input in pre-epileptic and epileptic rats, which might contribute to temporal lobe epileptogenesis., (Supported by NIH/NINDS)