Abstracts

The hilar ectopic granule cell (HEGC) is a neuron located in the hilus and has a morphology similar to that of granule cells found in the layer. Ultrastructural studies showed comparatively less inhibitory axons synapsing on HEGCs. This finding was consistent with electrophysiological data showing abnormal discharges of HEGCs synchronized with epileptiform bursts of pyramidal cells, indicating the participation of HEGCs in recurrent excitatory circuitry underlying epilepsy.
We hypothesized that two factors are responsible for the migration of granule cells into the hilus: hilar cell loss and increased neurogenesis. To address this hypothesis we studied the formation of HEGCs in four groups of rats: a) controls, b) rats subjected to a hypoxic/ischemic episode (hilar cell loss and increased neurogenesis without seizures), c) rats subjected to electroconvulsive shock (increased neurogenesis without hilar cell loss), and d) rats subjected to an episode of pilocarpine-induced status epilepticus (hilar cell loss + increased neurogenesis + seizures). Granule cells (including HEGCs) were visualized after bulk retrograde loading of biocytin in brain slices obtained from the four groups of rats at different times after treatment. The number of HEGCs was analyzed in each group and compared with control rats.
[table1]Preliminary analysis showed that HEGCs from rats with electroconvulsive shock were 1.9% of the total number of labeled granule cells in the layer, whereas those from the ischemic group were 5% of the cells. HEGCs were 0.8% of the granule cells in control animals. Lastly, preparations from rats sacrificed at 3, 8 and 21 days after pilocarpine-induced epilepsy showed that 0.9%, 5.9% and 5.7% of labeled granule cells were located in the hilus, respectively.
The data show that the experimental group with increased neurogenesis alone has an increased number of HEGCs compared to the control group. In contrast, the ischemic rats had a greater increase in the number of HEGCs, indicating that hilar cell loss may be a more effective stimulus for granule cells to migrate into the hilus. The epileptic rats examined 1-3 weeks following status epilepticus also had the same number of HEGCs as the ischemic rat group, indicating that both increased neurogenesis and hilar cell loss are involved in granule cell migration into the hilus. It should be noted that the control group was not significantly different from the rats with three days after status epilepticus, a time point when another neuroplastic change, the hilar basal dendrite, is not yet developed. These results provide evidence that hilar neuronal loss plays an important role in the abnormal migration of granule cells into the hilus.
[Supported by: NIH Grant NS-38331]