Projects: Aging and Cognition CaMKII and learning Cognitive enhancements Cortical memories Enhancing plasticity and recovery Learning disabilities Memory allocation Novel memory genes Schizophrenia Science of Science	Structure of aCaMKII CaMKII and learning Over the last 15 years our laboratory has engineered and analyzed a number of CaMKII mutations that helped to illuminate how this kinase regulates synaptic function and learning and memory. More recently, we have focused our attention on the  functional implications of the complex interactions between this kinase and post-synaptic density proteins, as well as on the role of this kinase in cortical memory formation.  The idea of these studies is to leverage the wealth of information concerning the beautifully intricate biochemistry of this kinase, in studies of synaptic mechanisms of learning and memory.
Key references: Matynia, A., S.G. Anagnostaras, B.J. Wiltgen, M. Lacuesta, M.S. Fanselow, and A.J. Silva, A high through-put reverse genetic screen identifies two genes involved in remote memory in mice. PLoS ONE, 2008. 3(5): p. e2121.(Click Here) Hojjati MR, van Woerden GM, Tyler WJ, Giese KP, Silva AJ, Pozzo-Miller L, Elgersma Y. Kinase activity is not required for alphaCaMKII-dependent presynaptic plasticity at CA3-CA1 synapses. Nat Neurosci 2007; 10(9): 1125-7.  Zhou, Y., Takahashi, E., Li, W., Halt, A., Wiltgen, B., Ehninger, D., Li, G.D., Hell, J.W., Kennedy, M.B., and Silva, A.J. (2007). Interactions between the NR2B receptor and CaMKII modulate synaptic plasticity and spatial learning. J Neurosci 27, 13843-13853.(PDF) Jin-Hee Han, Steven A. Kushner, Adelaide P. Yiu, Christy A. Cole, Anna Matynia, Robert A. Brown, Rachael Neve, John F. Guzowski, Alcino J. Silva, Sheena A. Josselyn. Neuronal competition and selection during memory formation. Science 2007, 31: 457-460(PDF). Ohno, M., W. Tseng, A.J. Silva, and J.F. Disterhoft, Trace eyeblink conditioning requires the hippocampus but not autophosphorylation of alphaCaMKII in mice. Learn Mem, 2005. 12(3): p. 211-5. Ohno, M., W. Tseng, A.J. Silva, and J.F. Disterhoft, Trace eyeblink conditioning requires the hippocampus but not autophosphorylation of alphaCaMKII in mice. Learn Mem, 2005. 12(3): p. 211-5. Zeitz, K.P., K.P. Giese, A.J. Silva, and A.I. Basbaum, The contribution of autophosphorylated alpha-calcium-calmodulin kinase II to injury-induced persistent pain. Neuroscience, 2004. 128(4): p. 889-98. Frankland, P.W., Josselyn, S.A., Anagnostaras, S.G., Kogan, J.H., Takahashi, E., and Silva, A.J. (2004). Consolidation of CS and US representations in associative fear conditioning. Hippocampus 14, 557-569. (PDF) Murphy GG, Fedorov NB, Giese KP, Ohno M, Friedman E, Chen R, Silva AJ. Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice. Curr Biol. 2004 Nov 9;14(21):1907-15.(PDF) Josselyn, S., Kida, S., and Silva, A. (2004). Inducible Repression of CREB Function Disrupts Amygdala-Dependent Memory. Neurobiology of Learning and Memory 82, 159-163. (PDF) Suzuki, A., Josselyn, S.A., Frankland, P.W., Masushige, S., Silva, A.J., and Kida, S. (2004). Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J Neurosci 24, 4787-4795. Frankland, P., B. Bontempi, L. Talton, L. Kaczmarek, and A. Silva, The anterior cingulate cortex is critical for remote contextual fear memory, 2004. Science 304, 881-3.(PDF) Taha, S., J. Hanover, A. Silva, and M.P. Stryker, Autophosphorylation of alpha CaMKII is required for ocular dominance plasticity. Neuron, 2002. 36(3): p. 483-491. Elgersma, Y., N. Fedorov, S. Ikonen, E. Choi, M. Elgersma, O. Carvalho, K. Giese, and A. Silva, Inhibitory autophosphorylation of CaMKII controls PSD association, plasticity and learning. Neuron, 2002. 36(3): p. 493-505.(PDF) Ohno, M., P. Frankland, and A. Silva, Pharmacogenetic inducible approach to the study of NMDA/aCaMKII  signaling  in synaptic plasticity. Current Biology, 2002. 12(8): p. 654-656.(PDF) Ohno, M., P.W. Frankland, A.P. Chen, R.M. Costa, and A.J. Silva, Inducible, pharmacogenetic approaches to the study of learning and memory. Nature Neuroscience, 4, 1238-43, 2001.(PDF)  Frankland, P., C. O'Brien, M. Ohno, A. Kirkwood, and A. Silva, CaMKII-Dependent Plasticity in the neocortex is required for remote memory. Nature, 2001. 411: p. 309-13.(PDF) Glazewski, S., K. Giese, A. Silva, and K. Fox, The role of alpha- CaMKII autophosphorylation in neocortical experience-dependent plasticity. Nature Neuroscience, 2000. 3: p. 911-918. Cho, Y.H., K.P. Giese, H. Tanila, A.J. Silva, and H. Eichenbaum, Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice. Science, 1998. 279(5352): p. 867-9. Giese, K.P., N.B. Fedorov, R.K. Filipkowski, and A.J. Silva, Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science, 1998. 279(5352): p. 870-3.(PDF) Kirkwood, A., A. Silva, and M.F. Bear, Age-dependent decrease of synaptic plasticity in the neocortex of alphaCaMKII mutant mice. Proc Natl Acad Sci U S A, 1997. 94(7): p. 3380-3.(PDF) Silva, A.J., T.W. Rosahl, P.F. Chapman, Z. Marowitz, E. Friedman, P.W. Frankland, V. Cestari, D. Cioffi, T.C. Südhof, and R. Bourtchuladze, Impaired learning in mice with abnormal short-lived plasticity. Current Biology, 1996. 6(11): p. 1509-18. Gordon, J.A., D. Cioffi, A.J. Silva, and M.P. Stryker, Deficient plasticity in the primary visual cortex of alpha-calcium/calmodulin-dependent protein kinase II mutant mice. Neuron, 1996. 17(3): p. 491-9. Glazewski, S., C.M. Chen, A. Silva, and K. Fox, Requirement for alpha-CaMKII in experience-dependent plasticity of the barrel cortex. Science, 1996. 272(5260): p. 421-3. Butler, L.S., A.J. Silva, A. Abeliovich, Y. Watanabe, S. Tonegawa, and J.O. McNamara, Limbic epilepsy in transgenic mice carrying a Ca2+/calmodulin-dependent kinase II alpha-subunit mutation. Proceedings of the National Academy of Sciences of the United States of America, 1995. 92(15): p. 6852-5. Chapman, P.F., B.G. Frenguelli, A. Smith, C.M. Chen, and A.J. Silva, The alpha-Ca2+/calmodulin kinase II: a bidirectional modulator of presynaptic plasticity. Neuron, 1995. 14(3): p. 591-7. Silva, A.J., R. Paylor, J.M. Wehner, and S. Tonegawa, Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science, 1992. 257(5067): p. 206-11. Silva, A.J., C.F. Stevens, S. Tonegawa, and Y. Wang, Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science, 1992. 257(5067): p. 201-6.
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