Neurogenesis in the dentate gyrus of age-matched calcium ion channel mutant mice, leaner and tottering

Homozygous leaner and tottering mice have a mutation in the alpha-1A subunit, which cause a decrease in calcium ion current through these channels leading to altered calcium homeostasis. These channels are highly expressed in several areas of the brain including the hippocampus. Neurogenesis in adults happens only in two specific areas: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Since P/Q-type channels are highly expressed in the hippocampus, we expect altered calcium homeostasis might affect neural proliferation in the mutant mice. The aims of this thesis were: (1) to determine if there was a decrease in neural proliferation in the dentate gyrus of adult leaner and tottering mice when compared to age-matched wild-type mice and (2) to determine if the new cells are neurons or glial cells and if there is a difference in proportion when compared to wild-type mice. We used bromodeoxyuridine (BrdU) to label the new cells. We examined proliferation rates in 100-150 day old mice and in 42-50 day old mice. We doublelabeled some newly formed cells using two different fluorescent tags to determine if the cells were neurons or glial cells. These studies showed that cell proliferation is indeed decreased in leaner and tottering mice at three months of age when compared to the wild-type mice. However, when we looked at mice that were 42-50 days old, we found a significant increase in cell proliferation in leaner and tottering mice compared to agematched control mice. When we looked at the proportion of double-labeled cells (neurons versus glia), there was no difference among genotypes for either age group. For both age-groups, there were about 90% new neurons and 20% new glial cells for the P100-150 mice and 85% new neurons and 10% new glial cells for the P42-50 mice. Since we do not see a change in proportion of double-labeled cells at either age group, it is probable that differentiation patterns are not being affected. Based on these observations, we predict that the altered calcium homeostasis that is probably occurring in the mutant mice is affecting cell proliferation, but not differentiation.