Abstracts

RATIONALE: At the end of this activity participants should be able to discuss the morphological characteristics of epileptic and control newborn dentate granule cells.
The birth of new neurons in the adult rat dentate gyrus occurs throughout life and is known to increase significantly in the period immediately following a seizure event. Little is known of the fate of these newly generated neurons in the epileptic brain, specifically, how ongoing seizure activity may impact the development and subsequent morphology of these cells and how their presence may contribute to the chronic epileptic state. The purpose of the present study was to study the morphology of these cells several weeks following their birth in control and epileptic animals.
METHODS: Five days following pilocarpine-induced status epilepticus (n = 3) or sham treatment (n = 3), a retroviral vector carrying a GFP transgene was injected into the subgranular zone of the dentate gyrus. Animals were allowed to survive 3-5 weeks post-injection before transcardial perfusion with a 4% paraformaldehyde solution. Brains were sectioned and coverslipped with an anti-fade mounting medium containing a DAPI counterstain.
RESULTS: GFP+ cells within the dentate granule cell (DGC) layer were selected for analysis using confocal microscopy at 400-600X. By three to five weeks following injection, GFP+ cells within the granule layer appeared fully differentiated, with complex dendritic arbors, oval somata and visible axons. For the most part, GFP+ DGCs appeared similar between control and epileptic rats. Distinguishing the two groups, however, was the observation that 27% (4/15) of GFP+ cells in epileptic rats exhibited a clear basal dendrite extending into the hilus. No GFP+ cells from control rats were observed to have this profile (0/15).
CONCLUSIONS: Observations of hilar basal dendrites are consistent with previous reports demonstrating the presence of this morphology in 5-12 % of DGCs of epileptic rats (Ribak et al. JCN 428:240, 2000; Buckmaster and Dudek J. Neurophysiol. 81:712, 1999). This phenotype could enhance recurrent excitation within the hippocampus and may contribute to the hyperexcitable state present in epileptic animals. However, given that newborn cells comprise only a small subset of the total population of DGCs, and the relatively low percentage of basal dendrites we found in GFP+ cells, it is unlikely newly generated neurons were the sole source of basal dendrites found in the DGCs of epileptic rats reported in previous studies.
[Supported by: NIH-NINDS Grants NS-32403 and NS-38572 to D.A.C.
NIH- R01-NS--39950 to D.H.L]