title: Primary cilia regulate proliferation of amplifying progenitors in adult hippocampus: implications for learning and memory.
abstract: 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 maintenance of adult NSCs is unknown. We developed a genetic mouse model in which fetal/perinatal brain development is unaffected, but adult 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 the new representations of spatial memories and that reduction of adult hippocampal neurogenesis may be 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.
authors: Department of Stem Cells and Regeneration, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA. aamador@sanfordburnham.org
authors: Alejandro
authors: A
authors: Amador-Arjona
authors: Jimmy
authors: J
authors: Elliott
authors: Amber
authors: A
authors: Miller
authors: Ashley
authors: A
authors: Ginbey
authors: Gregory J
authors: GJ
authors: Pazour
authors: Grigori
authors: G
authors: Enikolopov
authors: Amanda J
authors: AJ
authors: Roberts
authors: Alexey V
authors: AV
authors: Terskikh
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D002923:Cilia / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D020287:In Situ Nick-End Labeling / Q000379:methods; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D013550:Swimming / Q000523:psychology; D014163:Transfer, Psychology / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; C514104:Ift20 protein, mouse; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009479:Neuropeptides; D018809:Proliferating Cell Nuclear Antigen; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine