title: Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis.
abstract: Following their birth in the adult hippocampal dentate gyrus, newborn progenitor cells migrate into the granule cell layer where they differentiate, mature, and functionally integrate into existing circuitry. The hypothesis that adult hippocampal neurogenesis is physiologically important has gained traction, but the precise role of newborn neurons in hippocampal function remains unclear. We investigated whether loss of new neurons impacts dendrite morphology and glutamate levels in area CA3 of the hippocampus by utilizing a human GFAP promoter-driven thymidine kinase genetic mouse model to conditionally suppress adult neurogenesis. We found that chronic ablation of new neurons induces remodeling in CA3 pyramidal cells and increases stress-induced release of the neurotransmitter glutamate. The ability of persistent impairment of adult neurogenesis to influence hippocampal dendrite morphology and excitatory amino acid neurotransmission has important implications for elucidating newborn neuron function, and in particular, understanding the role of these cells in stress-related excitoxicity.
authors.affiliation: Mood and Anxiety Disorders Program, National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schloesser
authors.forename: Dennisse V
authors.initials: DV
authors.lastname: Jimenez
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Hardy
authors.forename: Daniel
authors.initials: D
authors.lastname: Paredes
authors.forename: Briony J
authors.initials: BJ
authors.lastname: Catlow
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.forename: Ronald D
authors.initials: RD
authors.lastname: McKay
authors.forename: Keri
authors.initials: K
authors.lastname: Martinowich
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000188:drug therapy; D018891:Dentate Gyrus / Q000473:pathology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D017966:Pyramidal Cells / Q000254:growth & development / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D018698:Glutamic Acid