title: Conditional deletion of α-CaMKII impairs integration of adult-generated granule cells into dentate gyrus circuits and hippocampus-dependent learning.
abstract: New granule cells are continuously integrated into hippocampal circuits throughout adulthood, and the fine-tuning of this process is likely important for efficient hippocampal function. During development, this integration process is critically regulated by the α-calcium/calmodulin-dependent protein kinase II (α-CaMKII), and here we ask whether this role is conserved in the adult brain. To do this, we developed a transgenic strategy to conditionally delete α-CaMKII from neural progenitor cells and their progeny in adult mice. First, we found that the selective deletion of α-CaMKII from newly generated dentate granule cells led to an increase in dendritic complexity. Second, α-CaMKII deletion led to a reduction in number of mature synapses and cell survival. Third, consistent with altered morphological and synaptic development, acquisition of one-trial contextual fear conditioning was impaired after deletion of α-CaMKII from newly generated dentate granule cells. Previous work in Xenopus identified α-CaMKII as playing a key role in the stabilization of dendritic and synaptic structure during development. The current study indicates that α-CaMKII plays a plays a similar, cell-autonomous role in the adult hippocampus and, in addition, reveals that the loss of α-CaMKII from adult-generated granule cells is associated with impaired hippocampus-dependent learning.
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
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, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Restivo
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Axel
authors.initials: A
authors.lastname: Guskjolen
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Epp
authors.affiliation: Department of Neuroscience, Erasmus MC University Medical Center, Rotterdam, The Netherlands, and.
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada, Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada, Department of Psychology, University of Toronto, Toronto, Ontario M5S 3G3, Canada.
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
authors.affiliation: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada, Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A8, Canada, Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada, Department of Psychology, University of Toronto, Toronto, Ontario M5S 3G3, Canada paul.frankland@sickkids.ca.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D003214:Conditioning, Classical; D018891:Dentate Gyrus / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D005239:Fear; D017353:Gene Deletion; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D018782:Maze Learning; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517671:Camk2a protein, mouse
keywords: CaMKII; adult neurogenesis; hippocampus