title: Temporal and region-specific requirements of αCaMKII in spatial and contextual learning.
abstract: The α isoform of the calcium/calmodulin-dependent protein kinase II (αCaMKII) has been implicated extensively in molecular and cellular mechanisms underlying spatial and contextual learning in a wide variety of species. Germline deletion of Camk2a leads to severe deficits in spatial and contextual learning in mice. However, the temporal and region-specific requirements for αCaMKII have remained largely unexplored. Here, we generated conditional Camk2a mutants to examine the influence of spatially restricted and temporally controlled expression of αCaMKII. Forebrain-specific deletion of the Camk2a gene resulted in severe deficits in water maze and contextual fear learning, whereas mice with deletion restricted to the cerebellum learned normally. Furthermore, we found that temporally controlled deletion of the Camk2a gene in adult mice is as detrimental as germline deletion for learning and synaptic plasticity. Together, we confirm the requirement for αCaMKII in the forebrain, but not the cerebellum, in spatial and contextual learning. Moreover, we highlight the absolute requirement for intact αCaMKII expression at the time of learning.
authors.affiliation: Department of Psychiatry.
authors.forename: Katharina G
authors.initials: KG
authors.lastname: Achterberg
authors.affiliation: Department of Neuroscience, and.
authors.forename: Gabriëlle H S
authors.initials: GH
authors.lastname: Buitendijk
authors.affiliation: Department of Neuroscience, and ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands, and.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Kool
authors.affiliation: Department of Neuroscience, and ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands, and.
authors.forename: Susanna M I
authors.initials: SM
authors.lastname: Goorden
authors.affiliation: Department of Neuroscience, and.
authors.forename: Laura
authors.initials: L
authors.lastname: Post
authors.affiliation: Department of Psychiatry.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Slump
authors.affiliation: Departments of Neurobiology, Psychiatry, Psychology, and Brain Research Institute, University of California, Los Angeles, California 90095.
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
authors.affiliation: Department of Neuroscience, and ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands, and.
authors.forename: Geeske M
authors.initials: GM
authors.lastname: van Woerden
authors.affiliation: Department of Psychiatry, s.kushner@erasmusmc.nl y.elgersma@erasmusmc.nl.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kushner
authors.affiliation: Department of Neuroscience, and ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus University Medical Center, 3015 GE, Rotterdam, The Netherlands, and s.kushner@erasmusmc.nl y.elgersma@erasmusmc.nl.
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D017774:Long-Term Potentiation / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004965:Estrogen Antagonists; D018398:Homeodomain Proteins; D019426:Integrases; D009419:Nerve Tissue Proteins; D013629:Tamoxifen; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C091104:Purkinje cell protein L7; C517671:Camk2a protein, mouse; C045073:Cre recombinase
keywords: CaMKII; cerebellum; fear conditioning; hippocampus; learning; spatial learning