title: Posttraining ablation of adult-generated olfactory granule cells degrades odor-reward memories.
abstract: Proliferation of neural progenitor cells in the subventricular zone leads to the continuous generation of new olfactory granule cells (OGCs) throughout life. These cells synaptically integrate into olfactory bulb circuits after ∼2 weeks and transiently exhibit heightened plasticity and responses to novel odors. Although these observations suggest that adult-generated OGCs play important roles in olfactory-related memories, global suppression of olfactory neurogenesis does not typically prevent the formation of odor-reward memories, perhaps because residual OGCs can compensate. Here, we used a transgenic strategy to selectively ablate large numbers of adult-generated OGCs either before or after learning in mice. Consistent with previous studies, pretraining ablation of adult-generated OGCs did not prevent the formation of an odor-reward memory, presumably because existing OGCs can support memory formation in their absence. However, ablation of a similar cohort of adult-generated OGCs after training impaired subsequent memory expression, indicating that if these cells are available at the time of training, they play an essential role in subsequent expression of odor-reward memories. Memory impairment was associated with the loss of adult-generated OGCs that were >10 d in age and did not depend on the developmental stage in which they were generated, suggesting that, once sufficiently mature, OGCs generated during juvenility and adulthood play similar roles in the expression of odor-reward memories. Finally, ablation of adult-generated OGCs 1 month after training did not produce amnesia, indicating that adult-generated OGCs play a time-limited role in the expression of odor-reward memories.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and Institute of Medical Science and.
authors.forename: Maithe
authors.identifier: http://orcid.org/0000-0002-7832-3729
authors.initials: M
authors.lastname: Arruda-Carvalho
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and.
authors.forename: Katherine G
authors.identifier: http://orcid.org/0000-0002-4578-6575
authors.initials: KG
authors.lastname: Akers
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and Departments of Physiology and.
authors.forename: Axel
authors.initials: A
authors.lastname: Guskjolen
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and Institute of Medical Science and Departments of Physiology and Psychology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8.
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8, and Institute of Medical Science and Departments of Physiology and Psychology, University of Toronto, Toronto, Ontario, Canada, M5S 1A8 paul.frankland@sickkids.ca.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004167:Diphtheria Toxin / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D058953:Neural Stem Cells / Q000502:physiology*; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D012201:Reward; D012903:Smell / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D004167:Diphtheria Toxin; D004965:Estrogen Antagonists; D013629:Tamoxifen
keywords: adult neurogenesis; memory; olfactory