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.