Abstracts

Rationale: Adult hippocampal neurogenesis supports certain forms of spatial learning and memory, and is significantly reduced with aberrant connectivity in Mesial Temporal lobe epilepsy (MTLE), leading to the hypothesis that abnormal neurogenesis may play a causal role in learning and memory impairment in these patients. We used a combination of watermaze testing in both patients and a rodent model of MTLE to investigate this hypothesis.Methods: Using a virtual watermaze, we ascertained the patterns of spatial learning and memory deficits in patients with MRI positive hippocampal sclerosis and compared these to deficits seen using a Morris watermaze in kainate treated adult rats, in whom the level and quality of neurogenesis was also examined. We also treated separate groups of chronically epileptic animals with one month of oral fluoxetine, an SSRI found to increase hippocampal neurogenesis, or vehicle, prior to water maze training.Results: An identical pattern of deficits, consisting of specifically impaired allocentric, but not egocentric, spatial learning was identified in both animal and patient groups. This was associated with quantitatively reduced and qualitatively abnormal hippocampal neurogenesis in the kainate treated animals. Treatment with one month of oral Fluoxetine prior to training restored both hippocampal neurogenesis and allocentric spatial learning to normal in kainate treated rats.Conclusions: These findings suggest that altered neurogenesis may be an underlying mechanism of spatial learning impairment in MTLE and suggest that fluoxetine may have a role in treating learning deficits in these patients.