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Research
Enriching the environment of CaMKII^T286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP

Stephanie L. Parsley¹, Sara M. Pilgram³, Florentina Soto^3,4, K. Peter Giese^2,5, and Frances A. Edwards^1,6

¹ Department of Physiology, University College London, London, WC1E 6BT, United Kingdom; ² Wolfson Institute for Biomedical Research, UCL, London, WC1E 6BT, United Kingdom; ³ Max-Planck Institute for Experimental Medicine, Goettingen, D-37075 Germany

CaMKII^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 CaMKII 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 CaMKII^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 CaMKII-independent changes in both wild-type and mutant mice. Such changes may be subsequently reversed in wild-type animals via CaMKII-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 CaMKII^T286A mutant mice would then result in impairment of spatial learning.

⁴ Present addresses: Department of Biological Structure, University of Washington School of Medicine, Seattle, WA 98195, USA;

⁵ Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King’s College London, London SE5 8AF, UK.

⁶ Corresponding author.

E-mail f.a.edwards{at}ucl.ac.uk; fax 44-20-7383-7005.

Article published online in January 2007. Article and publication date are at http://www.learnmem.org/cgi/doi/10.1101/lm.356607

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