creativity and extraordinary cognition
Our laboratory has a long standing interest in the mechanisms underlying extraordinary cognitive function. For example, we have generated a number of mouse strains with dramatic enhancements in learning and memory.
Understanding the molecular, cellular and circuit mechanisms of enhancements in learning and memory will be key to understanding extraordinary problem solving. Insights into extraordinary learning and memory have lead us a step closer to a mechanistic understanding of the biological processes responsible for historically creative achievements.
Insights into extraordinary cognition have also led us to treatments for cognitive deficits. For example, our efforts to identify memory enhancing mutations in mice led us to null mutations in CCR5, the receptor for HIV! In turn, this discovery led us to a brand new way to understand cognitive deficits associated with HIV and to a treatment for these cognitive deficits. Our work showed that stimulation of CCR5, a memory suppressor, by viral proteins may account for some of the cognitive deficits associated with HIV. Additionally, our discovery of the plasticity and memory enhancements associated with CCR5 mutants led to the discovery of a strategy to enhance recovery after brain injury, which is currently in clinical trials!
Mary T. Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Nikita S. Thareja,Marcela Arenas, Efrat Kliper, Amos D. Korczyn, Efrat L. Kesner, Miou Zho, Shan Huang2, Tawnie K. Silva2, Noomi, Katz, Natan M. Bornstein, Alcino J. Silva, Esther Shohami, Stanley T. Carmichael. CCR5 is a therapeutic target to stimulate recovery in stroke and traumatic brain injury. Cell (in press)(PDF)
Caracciolo, L., M. Marosi, J. Mazzitelli, S. Latifi, Y. Sano, L. Galvan, R. Kawaguchi, S. Holley, M. S. Levine, G. Coppola, C. Portera-Cailliau, A. J. Silva and S. T. Carmichael (2018). "CREB controls cortical circuit plasticity and functional recovery after stroke." Nat Commun 9(1): 2250 (PDF)
Miou Zhou Stuart Greenhill Shan Huang Tawnie K Silva Yoshitake Sano Shumin Wu Ying Cai Yoshiko Nagaoka Megha Sehgal Denise J Cai Yong-Seok Lee Kevin Fox Alcino J Silva. CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory. DOI: http://dx.doi.org/10.7554/eLife.20985; Published December 20, 2016; Cite as eLife 2016;10.7554/eLife.209851. (PDF)
Kaneko M, Cheetham CE, Lee Y-S, Silva AJ, Stryker MP, Fox K. Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(44):19026-31. PubMed PMID: Medline:20937865. (Link)
Kushner, S.A., Y. Elgersma, G.G. Murphy, D. Jaarsma, G.M. van Woerden, M.R. Hojjati, Y. Cui, J.C. LeBoutillier, D.F. Marrone, E.S. Choi, C.I. De Zeeuw, T.L. Petit, L. Pozzo-Miller, and A.J. Silva, Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway. J Neurosci, 2005. 25(42): p. 9721-34. (PDF)
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)
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)