Long-term adrenalectomy (ADX) results in a specific loss of dentate gyrus granule cells in the hippocampus of adult rats, occurring over a period of weeks to months. This loss of granule cells results in cognitive deficits in a number of tasks that depend on intact hippocampal function. The gradual nature of ADX-induced cell death and the ensuing deficits in cognition are similar to those experienced by patient populations suffering from a variety of pathological conditions. Here we present an animal model by which we use ADX to produce a loss of granule cells within the hippocampus of rats. We also provide experimental evidence for a treatment strategy by which the lost granule cells may be replaced, with the goal of functional recovery in mind. / xii, 191 leaves : ill. (chiefly col.) ; 28 cm

Adrenalectomy (ADX) has been shown to cause selective degeneration of granule cells in the dentate gyrus (DG). This occurs due to the reduction of corticosterone (CORT) and behavioural deficits are associated with the loss of these neurons. Dentate lesions and cell loss associated with ADX have been shown to effect behaviour in a number of spatial tasks. In contras, it has been shown granule cell loss does not affect the specificity of place cells in CA3 and CA1. We used the ADX model to examine the role of DG granule cells plays in representing space using immediate early gene (IEG) activation in the principal hippocampal subfields after exploration of novel environments. Rats were allowed to free explore multiple novel environments and then the mRNA for the IEG Homer 1a (H1a) was used as a marker of neural activity. After degeneration of approximately half of the DG granule cells we found a significant increase in number of active cells in the DG, CA3 and CA1 in ADX animals. The results indicate a reduction in granule cells causes a dramatic increase in the proportion of remaining DG granule cells in response to exploration. The change in DG activation disrupts the representations in CA3 and CA1 and thereby affects behaviour. / vii, 60 leaves : ill. (some col.) ; 29 cm

This study sought to determine whether the DG, CA3, and CA1 regions contain uniformly excitable populations and test the hypothesis that rapid addition of new, more excitable, granule cells in prepubescence results in a low activation probability (P1) in the DG. The immediate-early gene Homer1a was used as a neural activity marker to quantify activation in juvenile (P28) and adult (~5 mo) rats during track running. The main finding was that P1 in juveniles was substantially lower not only the DG, but also CA3 and CA1. The P1 for a DG granule cell was close to 0 in juveniles, versus 0.58 in adults. The low P1 in juveniles indicates that sparse, but non-overlapping, subpopulations participate in encoding events. Since sparse, orthogonal coding enhances a network’s ability to decorrelate input patterns (Marr, 1971; McNaughton & Morris, 1987), the findings suggest that juveniles likely possess greatly enhanced pattern separation ability. / ix, 51 leaves : ill. ; 29 cm