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Abstract
Most of the neurons in the mammalian brain do not proliferate in the mature brain. However, few neurons are thought to be produced during our lifetime within specific niche regions, in a process termed neurogenesis. One such region is the dentate gyrus (DG) of the hippocampus. We have previously shown that knocking out the eukaryotic elongation factor 2 (eEF2) kinase (eEF2K; or CaMKIII) in mice, leads to increased expression of a specific set of proteins as well as neurogenesis in the DG. Importantly, eEF2 is the only known substrate of eEF2K at Thr-56, whereas phosphorylation at this site inhibits eEF2 activity and rate of mRNA translation elongation. In addition, better context discrimination was detected at the behavioral level. So far, research has consistently shown that neurogenesis induction prior to learning improves it. However, mixed results have been reported when neurogenesis is induced post learning.
In my thesis, I induced neurogenesis in the DG of mice using eEF2K KO floxed mice, both before and after learning, and found better context discrimination and higher neurogenesis levels. These results suggest that enhanced neurogenesis one month following learning does not interfere with retrieving contextual memories that were previously acquired. Furthermore, enhancing eEF2 activity is beneficial for both learning and retrieval, and thus can be a valid target for the treatment of dementia and cognitive deterioration associated with age.
