Abstracts

Rationale: Anatomical changes have been noted in the dentate gyrus of aged rodents which may affect the balance of inhibition/excitation. Among these changes are a loss of GAD-immunoreactive neurons (Shetty and Turner, JCN, 394:252-69) and synaptic reorganization within the molecular layer (Rapp et al., JCN, 403:459-70). Since the dentate gyrus plays a critical role in regulating the onset and spread of seizure activity into the hippocampus, we have begun to examine the functional consequences of these changes. Methods: Whole cell current clamp recordings of granule cells were obtained in transverse hippocampal slices (400 ?m) prepared from adult (1-10 mo) and aged (23-32 mo) F344 rats. Membrane properties, spontaneous activity, and polysynaptically evoked IPSPs were examined. Results: No significant differences were noted in the membrane properties between groups. However, a decrease in the frequency of spontaneous activity, predominantly IPSPS, was observed in aged (n = 14) vs adult (n=13) granule cells (0.7 ?0.2 Hz vs 1.8 ? 0.2 Hz respectively; p<0.04) in normal ACSF using potassium methylsulfate electrodes. A similar decrease in IPSP frequency was observed in aged (n=10) vs adult (n=10) granule cells using KCl-patch electrodes (4.6 ?0.9 Hz vs 8.6 ? 1.6 Hz; p<0.05). When polysynaptically evoked IPSPs were compared between groups no significant differences were noted, although a trend existed for decreased fast (9.1 ? 1.1 nS vs 13.3 ? 3.3 nS) and slow (2 ? 0.4 nS vs 2.6 ? 0.7 nS) IPSP conductances in granule cells (n=16) from aged rodents vs adults (n=16 cells). When spontaneous and evoked activity was examined in the presence of bicuculline (30 ?M) a striking difference was noted in the proportion of granule cells from aged rats that displayed large complex EPSPs lasting 50-200 ms (10 of 19 cells; 53%) relative to that observed in adult slices (1 of 8 cells; 13%). Conclusions: These preliminary studies support prior anatomical data suggesting alterations in local dentate circuitry during aging. These changes may contribute to altered hippocampal function during aging (i.e. seizure susceptibility and synaptic plasticity). Supported by NIH grant AG00795