Conditional Deletion of alpha-CaMKII Impairs Integration of Adult-Generated Granule Cells into Dentate Gyrus Circuits and Hippocampus-Dependent Learning

New granule cells are continuously integrated into hippocampal circuits throughout adulthood, and the fine-tuning of this process is likely important for efficient hippocampal function. During development, this integration process is critically regulated by the alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII), and here we ask whether this role is conserved in the adult brain. To do this, we developed a transgenic strategy to conditionally delete alpha-CaMKII from neural progenitor cells and their progeny in adult mice. First, we found that the selective deletion of alpha-CaMKII from newly generated dentate granule cells led to an increase in dendritic complexity. Second, alpha-CaMKII deletion led to a reduction in number of mature synapses and cell survival. Third, consistent with altered morphological and synaptic development, acquisition of one-trial contextual fear conditioning was impaired after deletion of alpha-CaMKII from newly generated dentate granule cells. Previous work in Xenopus identified alpha-CaMKII as playing a key role in the stabilization of dendritic and synaptic structure during development. The current study indicates that alpha-CaMKII plays a plays a similar, cell-autonomous role in the adult hippocampus and, in addition, reveals that the loss of alpha-CaMKII from adult-generated granule cells is associated with impaired hippocampus-dependent learning

Data from: Hippocampal neurogenesis regulates forgetting during adulthood and infancy

Throughout life, new neurons are continuously added to the dentate gyrus. As this continuous addition remodels hippocampal circuits, computational models predict that neurogenesis leads to degradation or forgetting of established memories. Consistent with this, increasing neurogenesis after the formation of a memory was sufficient to induce forgetting in adult mice. By contrast, during infancy, when hippocampal neurogenesis levels are high and freshly-generated memories tend to be rapidly forgotten (infantile amnesia), decreasing neurogenesis after memory formation mitigated forgetting. In precocial species, including guinea pigs and degus, the majority of granule cells are generated prenatally. Consistent with reduced levels of postnatal hippocampal neurogenesis, infant guinea pigs and degus did not exhibit forgetting. However, increasing neurogenesis after memory formation induced infantile amnesia in these species

Data from Fig. 1H and Fig. S3b

Data from Fig. 1H and Fig. S3

Data from Fig. S16bcde

Data from Fig. S16bcd

Data from Fig. S3de

Data from Fig. S3d