Figure 6.

Immature DG of Alpha-CaMKII+/- Mice. (A) Cells proliferate in the subgranular layer (SGL), and migrate and differentiate into mature neurons in the granular layer (GL) in the adult hippocampus. Each stage of the neuronal development has cell markers and specific morphological and physiological properties. In the DG of alpha-CaMKII+/- mice, the number of cells expressing Polysialic acid-NCAM (PSA-NCAM), a marker for late-stage progenitor cells and immature neurons, and calretinin, a marker for immature neurons, was dramatically increased, whereas the amount of calbindin, a marker for mature neurons in the DG, -positive cells was markedly reduced. Electrophysiological study of the DG neurons showed that input resistance was high and the number of spikes during sustained depolarization was decreased in mutant mice. Furthermore, morphological analysis revealed that dendritic branching and length were decreased in the mutant DG. Collectively, the mutant DG granule cells had many features that are characteristic of immature DG neurons. Red arrows represent the specific changes in the DG of alpha-CaMKII+/- mice. (B) A schematic model of gene-to-behavior pathways in alpha-CaMKII+/- mice. Alpha-CaMKII deficiency leads multiple abnormal gene expression and signal transduction, which causes "immature DG" and impaired function of hippocampus and other brain regions, resulting in abnormal behaviors of alpha-CaMKII+/- mice. Based on the finding that expression changes of genes related to neurogenesis and neural maturation/migration, including calbindin, in hippocampus is associated with higher incidence of schizophrenic patients, "Immature DG" and its equivalent hippocampal functional abnormalities may serve as a promising candidate endophenotype of psychiatric disorders, such as schizophrenia and bipolar disorders.