Enriching the environment of alphaCaMKIIT286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP.
alphaCaMKII(T286A) mutant mice lack long-term potentiation (LTP) in the hippocampal CA1 region and are impaired in spatial learning. In situ hybridization confirms that the mutant mice show the same developmental expression of alphaCaMKII as their wild-type littermates. A simple hypothesis would suggest that if LTP is a substrate for learning, then enriching the environment should cause learning-dependent changes in wild-type mice that have LTP. Such changes would not be seen in LTP-deficient alphaCaMKII(T286A) mutants. Excitatory synaptic currents in CA1 neurons, recorded with patch clamp in brain slices, revealed that enrichment induces an increase in glutamate release probability and a decreased miniature current amplitude. Confocal microscopy also showed dendritic spine density to be reduced. However, contrary to the hypothesis above, these enrichment-induced changes occur only in the mutant mice and are not detectable in wild-type littermates. We suggest that enrichment induces alphaCaMKII-independent changes in both wild-type and mutant mice. Such changes may be subsequently reversed in wild-type animals via alphaCaMKII-dependent mechanisms, such as LTP. Reversal of plasticity has long been hypothesized to be essential for the hippocampus to maintain its role in memory processing. The inability to reverse plasticity in alphaCaMKII(T286A) mutant mice would then result in impairment of spatial learning.
Parsley
Stephanie L
SL
Department of Physiology, University College London, London, United Kingdom.
Pilgram
Sara M
SM
Soto
Florentina
F
Giese
K Peter
KP
Edwards
Frances A
FA
D000225:Adenine; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D003712:Dendrites / Q000648:ultrastructure; D004777:Environment; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010988:Play and Playthings; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism; D009435:Synaptic Transmission; D013941:Thymine; D014018:Tissue Distribution
D012333:RNA, Messenger; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000225:Adenine; D013941:Thymine