Primary cilia regulate poliferation of amplifying progenitors in adult hippocampus: Implications for learning and memory

Integration of new neurons into the adult hippocampus has been linked to specific types of learning. Primary cilia were found to be required for the formation of adult neural stem cells (NSCs) in the hippocampal dentate gyrus during development. However, the requirement of cilia in maintenanceof adultNSCsisunknown.Wedevelopedageneticmousemodelinwhichfetal/perinatal braindevelopmentis unaffected,butadult hippocampal neurogenesis is constantly reduced by conditional ablation of primary cilia in adult GFAP⁺ neural stem/progenitor cells. We found that this approach specifically reduces the number of hippocampal amplifying progenitors (also called type 2a cells) without affecting the number of radial NSCs (or type 1 cells). Constant reduction of adult hippocampal neurogenesis produced a delay rather than a permanent deficiency in spatial learning without affecting the retention of long-term memories. Decreased neurogenesis also altered spatial novelty recognition and hippocampus-independent cue conditioning. Here, we propose that adult hippocampal newborn neurons increase the efficiency of generating thenewrepresentations of spatial memories and that reduction of adult hippocampal neurogenesismaybe biased toward cue-based strategies. This novel mouse model provides evidences that cognitive deficits associated with ciliary defects (ciliopathies) might be, in part, mediated by the deficiency of primary cilia in adult hippocampal stem/progenitor cells.