Cognitive problems associated with a wide range of medical problems, including neurodevelopmental disorders, aging-related conditions, neurodegenerative disorders and even conditions such as cancer and heart disease, represent the singular most serious unmet medical need. Alcino Silva’s laboratory is studying the molecular, cellular and circuit processes that underlie the encoding, allocation, storage and recall of information in the brain. They are using insights into mechanisms of memory to unravel the causes of cognitive deficits associated with aging, learning disabilities, autism and schizophrenia. The Silva lab has identified in mice adult treatments for the learning problems associated with neurodevelopmental disorders, including tuberous sclerosis and Neurofibromatosis type I. The insights obtained from these studies are bringing us closer than ever to developing general strategies to tackle the serious medical problems associated with cognitive deficits. His laboratory is also developing strategies to derive simplified useful representations of previous findings, (i.e. creating research maps that could be used for experiment planning).
Neurofibromin regulates corticostriatal inhibitory networks during working memory performance.
Shilyansky C, Karlsgodt KH, Cummings DM, Sidiropoulou K, Hardt M, James AS, Ehninger D, Bearden CE, Poirazi P, Jentsch JD, Cannon TD, Levine MS, Silva AJ. Proc Natl Acad Sci U S A. 2010 Jul 12. PMID: 20624961
The Hippocampus Plays a Selective Role in the Retrieval of Detailed Contextual Memories.
Wiltgen, B.J., M. Zhou, Y. Cai, J. Balaji, M.G. Karlsson, S.N. Parivash, W. Li, and A.J. Silva
Curr Biol. 2010. 20(15): p. 1336-1344. PMID: 20637623
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons.
Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G.
Nat Neurosci. 2010 Apr;13(4):423-30. PMID: 20228804
Increased Levels of Anxiety-related Behaviors in a Tsc2 Dominant Negative Transgenic Mouse Model of Tuberous Sclerosis.
Ehninger, D. and A.J. Silva Behav Genet. 2010
Zhou, M, Li, W, Huang, S, Song, J, Kim, J Tian, X, Kang, E Sano, Y, Liu, C, Balaji, J, Wu, S, Zhou, Y, Zhou, Y, Parivash, S, Ehninger, D, He, L. Song, H, 3, Ming, G, Silva AJ mTOR Inhibition Ameliorates Cognitive and Affective Deficits Caused by Disc1 Knockdown Specifically in Adult-Born Dentate Granule Neurons. Neuron 77, 647–654, 2013
Landreth, A. and Silva, A.J. The Need for Research Maps to Navigate Published Work and Inform Experiment Planning. Neuron 2013 79 411-415