title: Experience-dependent increase in CA1 place cell spatial information, but not spatial reproducibility, is dependent on the autophosphorylation of the alpha-isoform of the calcium/calmodulin-dependent protein kinase II.
abstract: Place cells in hippocampal area CA1 are essential for spatial learning and memory. Here, we examine whether daily exposure to a previously unexplored environment can alter place cell properties. We demonstrate two previously unreported slowly developing plasticities in mouse place fields: both the spatial tuning and the trial-to-trial reproducibility of CA1 place fields improve over days. We asked whether these two components of improved spatial coding rely on the alpha-isoform of the calcium/calmodulin-dependent protein kinase II (alphaCaMKII) autophosphorylation, an effector mechanism of NMDA receptor-dependent long-term potentiation and an essential molecular process for spatial memory formation. We show that, in mice with deficient autophosphorylation of alphaCaMKII, the spatial tuning of place fields is initially similar to that of wild-type mice, but completely fails to show the experience-dependent increase over days. In contrast, place field reproducibility in the mutants, although impaired, does show the experience-dependent increase over days. Consequently, the progressive improvement in spatial coding in new hippocampal place cell maps depends on the existence of two molecularly dissociable, experience-dependent processes.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom. f.cacucci@ucl.ac.uk
authors.forename: Francesca
authors.initials: F
authors.lastname: Cacucci
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wills
authors.forename: Colin
authors.initials: C
authors.lastname: Lever
authors.forename: Karl Peter
authors.initials: KP
authors.lastname: Giese
authors.forename: John
authors.initials: J
authors.lastname: O'Keefe
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000166:cytology*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology / Q000528:radiation effects; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases