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 Picasso	Ramon Cajal Aging and cognition Deficits in learning and memory (L&M) can occur with aging, but little is known about what causes them. Studies in our laboratory demonstrated that just as humans and other animals, mice show age-related deficits in a variety of learning tests. Interestingly, cells in the brain become progressively less excitable with age, and previous studies suggested that this decrease in excitability could cause deficits in learning and memory. Remarkably, our laboratory has shown that a change in a gene that increases the excitability of brain cells (the Kvb1.1 gene) improves synaptic plasticity (a candidate cellular mechanism for learning and memory) and learning and memory specifically in aged mice. We are engaged in a number of memory studies that will impact on how we understand and treat age-related cognitive decline, including studies of how the prefrontal cortex modulates the storage and retrieval of remote memory, and how memories are allocated in neuronetworks.
Key Reference Murphy, G., Shah, V.,. Hell, J.W., Silva, A.J. Investigation of age-related cognitive decline using mice as a model system: neurophysiological correlates. Am J Geriatr Psychiatry. 2006 Dec;14(12):1012-21. (PDF). Murphy, G., Shah, V.,. Hell, J.W., Silva, A.J. Investigation of age-related cognitive decline using mice as a model system: behavioral correlates. Am J Geriatr Psychiatry. 2006 Dec;14(12):1004-11.(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) Giese, K.P., J.F. Storm, D. Reuter, N.B. Fedorov, L.-R. Shao, T. Leicher, O. Pongs, and A.J. Silva, Reduced K+ channel inactivation, spike broadening, and after-hyperpolarization in Kvß1.1-deficient mice with impaired learning. Learning and Memory, 1998. 5: p. 257-273.
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