Long-term enrichment enhances the cognitive behavior of the aging neurogranin null mice without affecting their hippocampal LTP.
Neurogranin (Ng), a PKC substrate, is abundantly expressed in brain regions important for cognitive functions. Deletion of Ng caused severe deficits in spatial learning and LTP in the hippocampal CA1 region of mice. These Ng-/- mice also exhibit deficits in the amplification of their hippocampal signaling pathways critical for learning and memory. A short-term exposure to an enriched environment failed to improve their behavioral performances. Here, we showed that a long-term enrichment protocol for the aging mice was beneficial to the Ng-/- as well as Ng+/+ and Ng+/- mice in preventing age-related cognitive decline. Enrichment also caused an increase in the hippocampal CREB level of all three genotypes and Ng level of Ng+/+ and Ng+/- mice, but not that of alphaCaMKII or ERK. Interestingly, hippocampal slices of these enriched aging Ng-/- mice, unlike those of Ng+/+ and Ng+/- mice, did not show enhancement in the high frequency stimulation (HFS)-induced LTP in the CA1 region. It appears that the learning and memory processes in these enriched aging Ng-/- mice do not correlate with the HFS-induced LTP, which is facilitated by Ng. These results demonstrated that long-term enrichment for the aging Ng-/- mice may improve their cognitive function through an Ng-independent plasticity pathway.
Developmental Neuroscience Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510, USA. fhuang@mail.nih.gov
Freesia L
FL
Huang
Kuo-Ping
KP
Huang
Catherine
C
Boucheron
D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004779:Environment Design; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D051579:Neurogranin / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C496650:Nrgn protein, mouse; D051579:Neurogranin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1