Alcino J. Silva

Alcino J. Silva

Alcino Silva, UCLA 2008
Born Alcino Jose Silva
(1961-04-09) April 9, 1961
Marco de Canaveses Municipality, Portugal
Fields Neuroscience, Psychiatry and Psychology
Institutions UCLA
Alma mater Rutgers University
University of Utah
Massachusetts Institute of Technology
Doctoral advisor Raymond White
Known for Molecular cellular cognition of memory
Notable awards Medalha Marco Canavezes, Senior Roche Award for Translational Neuroscience, Order of Prince Henry, American Association for the Advancement of Science, UCLA Distinguished Professor
Spouse Tawnie Silva (2 children: Elenna Silva and Alexander Silva)

Alcino J. Silva (born April 9, 1961) is an American neuroscientist who was the recipient of the 2008 Order of Prince Henry and elected as a fellow of the American Association for the Advancement of Science in 2013 for his contributions to the Molecular cellular cognition of memory, a field he pioneered with the publication of two articles in Science (journal) in 1992.[1][2]

Silva is a Distinguished Professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA, director of the Integrated Center for Learning and Memory at UCLA and the Founding President of the Molecular and Cellular Cognition Society.

He is former Scientific Director of the Division of Intramural Research Programs (DIRP) at the National Institute of Mental Health (NIMH),[3] having also served as member of the Board of Regents of the University of Minho, Portugal.

Early years

Silva was born in Portugal in 1961, but spent his early years in Luanda, Angola. He left Africa when he was only 12 and in Portugal he went through the Carnation Revolution of 1974. He arrived in the United States in 1978, attended Rutgers University, where he studied biology and philosophy and worked in the Drosophila laboratory of William Sofer. After that he pursued graduate studies in Human Genetics at the University of Utah. There, he worked with Raymond White, one of the pioneers of modern Human Genetics.

His graduate work showed that epigenetic patterns of DNA methylation can be polymorphic and that they are inherited in a Mendelian fashion.[4] During his graduate studies he became intrigued by the inner processes of science, and organized yearly graduate symposia where leading scientists shared their insights on this subject. It was in Utah that he realized that he could combine his passion for biology with his interest in epistemology.[5] It was also in Utah, while working with Mario Capecchi, that he had the idea of bringing the newly developed mouse gene targeting approaches [6] to studies of memory. Capecchi shared the Nobel prize with Martin Evans and Oliver Smithies for the development of gene targeting strategies in mice.[7]

Post-doctoral work and early research at MIT

While at a meeting in Cold Spring Harbor Laboratory, Silva heard from Peter Mombaerts (now at the Max Planck Institute for Biophysics) that Susumu Tonegawa at MIT was interested in Neuroscience (Tonegawa had taken a Neuroscience course at CSHL in 1987), and that his lab was trying to set up gene targeting to study the immunology T-cell receptors they had cloned.[8] So, he wrote to Tonegawa and proposed to target genes expressed postnatally in the cerebellum to study cerebellar memory. At the time the Tonegawa laboratory at MIT was focused exclusively in immunology. Susumu Tomegawa was awarded a Nobel Prize in 1987 for his discovery of the genetic mechanism that produces antibody diversity.[9] Silva joined the Tonegawa laboratory in early fall of 1988.

After attending a Society for Neuroscience symposium (Toronto, 1988), organized by John Lisman on mechanisms of hippocampal plasticity, Silva decided to study hippocampal-dependent memory formation. The compelling properties of calcium calmodulin kinase II, one of the topics discussed in that symposium, and an elegant model by John Lisman proposing a key role for that kinase in hippocampal learning and memory,[10] persuaded Silva to refocus his project in the Tonegawa laboratory on the role of the alpha calcium calmodulin kinase II in hippocampal synaptic plasticity and learning & memory.[1][2] The two articles he published in Science as a post-doctural fellow in Susumu Tonegawa's laboratory were the first to combine molecular genetic techniques with electrophysiological analyses and behavioral studies.[11] This interdisciplinary integration of molecular, electrophysiological and behavioral approaches, fostered by transgenic techniques, has become a mainstay of neuroscience studies.

The Cold Spring Harbor Laboratory years

After spending three years in the Tonegawa laboratory, Silva set up his own laboratory at Cold Spring Harbor Laboratory in Long Island, New York, a research institute then run by James Watson, best known as the co-discoverer of the structure of DNA in 1953 with Francis Crick. Initially, the Silva laboratory focused its studies on molecular and cellular mechanisms of hippocampal learning and memory. For example, Rousudan Bourtchuladze led a project in the Silva laboratory that uncovered a role for the transcription factor CREB in the stability of hippocampal long term potentiation and long-term memory.[12] This was the first report of a genetic manipulation that affected the stability of synaptic plasticity and specifically long-. but not short-term memory.[13] Other notable studies of memory mechanisms in the early years of the Silva laboratory in Cold Spring Harbor included the discovery that hippocampal pre-synaptic short-term plasticity mechanisms have a role in hippocampal learning and memory.[14] This early work with hippocampal mutations that affected long term potentiation and learning & memory became the basis for a large literature that now has definitively implicated stable changes in synaptic plasticity in the hippocampal CA1 region in hippocampal dependent learning and memory.[15]

Move to UCLA

In 1998 the Silva laboratory moved to the Department of Neurobiology at the UCLA School of Medicine. There, the laboratory bridged their growing involvement in animal models of cognitive disorders with clinical studies. Additionally, UCLA's large and highly collaborative neuroscience community was an ideal environment for the interdisciplinary studies that characterized work in the Silva laboratory. The Silva laboratory became more involved in studying molecular and cellular mechanisms responsible for cognitive deficits in genetic neurodevelopmental disorders. In the late nineties, cognitive deficits associated with this class of disorders were thought to be caused by genetic disruptions of brain development [16][17] Animal model studies of Neurofibromatosis type I (NF1) in the Silva lab suggested that the learning and memory deficits associated with NF1 mutations are caused by changes in synaptic plasticity mechanisms in adults. Accordingly, a project led by Rui M. Costa in the Silva Lab demonstrated that the electrophysiological, and more importantly the behavioral deficits, caused by NF1 mutations could be reversed in adults by manipulations that corrected the molecular signaling deficits associated with these mutations.[18] This discovery, and a series of later studies in many laboratories worldwide, have demonstrated the surprising efficacy of adult interventions in reversing cognitive phenotypes in animal models of neurodevelopmental disorders.[16] Following the NF1 studies published in 2002 by the Silva laboratory,[18] other findings that reported adult rescue of neurodevelopment disorders include, for example, animal studies of Lhermitte-Duclos disease [19] and Rubinstein-Taybi syndrome in 2003,[20] Fragile X syndrome in 2005,[21] Down syndrome in 2007,[22] Rett syndrome [23] and Angelman syndrome in 2007,[24] Tuberous Sclerosis in 2008.[25]

Development of treatments for cognitive deficits in Neurofibromatosis type I and Tuberous Sclerosis

Weidong Li and Steven Kushner led a team in the Silva lab that developed a treatment for the cognitive deficits associated with an animal model of Neurofibromatosis type I (NF1).[26] They discovered that Lovastatin, a statin that crosses the blood-brain barrier, at a dose that does not affect control mice, rescues the Ras/MAPK signaling, synaptic plasticity and behavioral deficits of mice with a NF1 mutation.[27] Statins decrease the levels of isoprenyls, lipid groups that are required for the isoprenylation and activity of Ras,[28] a signaling molecule normally regulated by the protein encoded by the NF1 gene. The work in the Silva lab showed that the NF1 mutation leads to increases in the levels of active Ras in the brain, and that statins reverse this increase without affecting Ras signaling in controls. These results have led to a number of small promising, but inconclusive, clinical trials,[29][30][31] and to two large on going clinical studies in the USA and Europe.[32][33] A team led by Dan Ehninger in the Silva lab also showed that rapamycin, an FDA approved inhibitor of mTOR, can reverse the late-LTP deficits and learning impairments they discovered in an animal model of Tuberous Sclerosis (Tsc2 heterozygous mice).[34] Interestingly, TSC is highly associated with autism, but the Tsc2 heterozygous mice did not show any autism-like behavioral abnormalities, such as social interaction deficits. Artificially activating the immune system of pregnant mice, however, does reveal social interaction deficits in Tsc2 heterozygous progeny, suggesting that the autism-like symptoms in TSC require not only Tsc mutations, but also another factor, such as immune activation during pregnancy.[35] Importantly, analyses of human TSC data suggested a similar interaction between the TSC mutation and immuno-activation during pregnancy.[35] Recently, Miou Zhou and colleagues at the Silva lab found that rapamycin is also capable of both preventing and reversing behavioral deficits caused by mutation of a schizophrenia-causing gene (DISC 1) in neurons that are born and develop in adult mice (i.e., adult neurogenesis).[36] Surprisingly, rapamycin reverses behavioral deficits despite its inability to reverse structural deficits discovered in neurons with Disc 1 knock down. All together, these findings make a compelling case that adult treatments may be effective at reversing behavioral cognitive and psychiatric symptoms associated with neurodevelopmental disorders such as NF1, TSC and Schizophrenia.[37]

Mechanisms of remote memory

Until recently, research on molecular, cellular and system mechanisms of memory focused almost exclusively on the early stages (minutes, hours following training) of memory formation. Paul Frankland and colleagues in the Silva laboratory explored the molecular and cellular underpinnings of remote memory consolidation. They discovered one of the first molecular manipulations that disrupts specifically remote memory.[38][39] Strikingly, the remote memory mutation they described disrupts synaptic plasticity in neocortex, but not in the hippocampus, a result consistent with models proposing that the hippocampus can only support memory for a short time, and that remote memory depends on neocortical storage sites.[38] Frankland and colleagues also used a combination of genetic, imaging and reversible lesion approaches to search for regions in the neocortex that are involved in remote memory.[40] These studies indicated that unlike the hippocampus, prefrontal cortical regions, such as the anterior cingulate, have a critical role in remote, but not in recent memory retrieval.[39] Altogether, these studies opened the door to unraveling the molecular and cellular mechanisms that are responsible for the long-term storage of information in the brain. Once again, studies in the Silva Laboratory revealed the critical role of synaptic plasticity in learning and memory, this time in cortical memory storage [41]

Discovery of neuronal memory allocation

A team led by Sheena Josselyn in the Silva Lab discovered that there are molecular and cellular mechanisms that regulate which neurons in a circuit encode a given memory (neuronal memory allocation). They found that the transcription factor CREB modulates the probability that individual amygdala neurons become involved in storing a specific emotional memory: higher levels of CREB increase this probability while lower levels of CREB have the opposite effect.[42] Later, Yu Zhou and colleagues in the Silva lab discovered that CREB modulates memory allocation by regulating neuronal excitability.[43] These studies suggested that the mechanisms that consolidate one memory, for a limited period of time, may be involved in determining the allocation of the next memory.[44]

ResearchMaps for integrating and planning research

The growth of the scientific literature in the last 20 years has been unprecedented.[45] For example, the library of medicine now includes more than two million Neuroscience articles. Anthony Landreth and Alcino Silva have developed a strategy to derive maps (simplified abstraction) of published articles in Neuroscience that they think could be used to integrate and summarize with more clarity and objectivity what we know, what we are uncertain about and what we do not know in neuroscience.[46][47][48] They propose that these maps of research findings would also be invaluable during experiment planning: Understanding more objectively the implications of the millions of neuroscience papers already published would allow neuroscientists to more clearly define what to do next. Landreth and Silva propose that quantitative maps of research findings will be to experiment planning in neuroscience what statistics is to experiment analyses: a tool that will help neuroscientists judge the likelihood that a series of planned experiments will contribute to the research record. As a first step towards the generation of these maps, Landreth and Silva developed a way to classify the many millions of experiments in neuroscience into a small number of categories that are critical for the generation of these maps. To generate these maps, Landreth and Silva also developed a set of algorithms that formalize strategies neuroscientists use to determine the strength of evidence in their fields. These algorithms are used to represent the experiments in networks of causally connected phenomena (i.e., research maps). Pranay Doshi and colleagues in the Silva Lab developed a completely free app (www.ResearchMaps.org) that helps researchers generate these maps. Data from individual research articles is entered into a relational database, and the app can generate maps not only for experimental findings in single research articles, but also for combinations of findings associated with different articles. The user can query the app and tailor-make specific maps that can then be used for experiment planning.

Awards

Klingenstein Foundation, 1993

Beckman Young Investigators Award, Beckman Foundation, 1994[49]

Whitehall Foundation, 1994

Japan Society for the Promotion of Science, 1994.

Merck Foundation, 1995

McKnight Foundation, 1995

NIH-R01, 1995

NIH-P01, 1996

VW Foundation, 1996

Neurofibromatosis Consortium, 1996

Neurofibromatosis Foundation, 1996

Perkin Fund, 1997

Neurofibromatosis Foundation, 1997

NIH-RO1, 1998

Neurofibromatosis Inc, 1999

Fragile X Foundation Award, 1999

NIH-SNRP, 1999

NIH-RO1, 1999

NARSAD, 1999

NIH-RO1, 1999

Neurofibromatosis Inc, 2000

Neurofibromatosis Inc, 2001

NIH, NIA RO1, 2001

NIH, NINDS RO1, 2002

NF-CDMRP, 2002

Neurofibromatosis Inc, 2002

Tenenbaum Creativity Chair, 2004

NF-CDMRP, 2005

NF INC 2006

NIH, NIA Merit Award 2006

NIH, NIMH Conte Center 2006 (Director)

Tenenbaum Creativity Award, 2007

Adelson Foundation, 2007, 2008

Order of Prince Henry, 2008

Senior Roche Award For Translational Neuroscience,[50] 2009

Medal of Science, Marco Canavezes, Portugal, 2009

NIMH RO1 2010

Richard Merkin Foundation, 2011

Leslie Chair in Pioneering Brain Research, 2011

Adelson Foundation Award, 2012

Fellow, American Association for the Advancement of Science, 2012

Best Leader Award in Applied Science and Technology, 2014

UCLA Distinguished Professor, 2015

Selected publications

References

  1. 1 2 Silva AJ, Paylor R, Wehner JM, Tonegawa S (1992). "Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice". Science 257 (5067): 206–11. doi:10.1126/science.1321493. PMID 1321493.
  2. 1 2 Silva AJ, Stevens CF, Tonegawa S, Wang Y (1992). "Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice". Science 257 (5067): 201–6. doi:10.1126/science.1378648. PMID 1378648.
  3. ↑ "New Division Directors Come on Board at NIMH".
  4. ↑ Silva, A.J.; White, R. (1988). "Inheritance of allelic blueprints for methylation patterns". Cell 54 (2): 145–52. doi:10.1016/0092-8674(88)90546-6. PMID 2898978.
  5. ↑ Silva, A.J. and R. White, Thesis for a Ph.D. in the Department of Human Genetics, University of Utah: The genetics of human methylation. UMI, Bell and Howell Information Company, #3058. 1989.
  6. ↑ Thomas, K. R.; Capecchi, M. R. (1987). "Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells". Cell 51: 503–512. doi:10.1016/0092-8674(87)90646-5. PMID 2822260.
  7. ↑ "The Nobel Prize in Physiology or Medicine 2007". Nobelprize.org. Retrieved 2007-10-08.
  8. ↑ Mombaerts, P.; Clarke, A. R.; et al. (1992). "Mutations in T-cell antigen receptor genes alpha and ß block thymocyte development at different stages". Nature 360: 225–231. doi:10.1038/360225a0.
  9. ↑ "The MIT 150: 150 Ideas, Inventions, and Innovators that Helped Shape Our World". The Boston Globe. May 15, 2011. Retrieved August 8, 2011.
  10. ↑ Lisman, J. E.; Goldring, M. A. (1988). "Feasibility of long-term storage of graded information by the Ca2+/calmodulin-dependent protein kinase molecules of the postsynaptic density". Proc Natl Acad Sci U S A 85 (14): 5320–5324. doi:10.1073/pnas.85.14.5320.
  11. ↑ Grant, S.G. and A.J. Silva, Targeting learning. Trends Neurosci 1994; 17(2): p. 71-5.
  12. ↑ Bourtchuladze, R.; Frenguelli, B.; Blendy, J.; Cioffi, D.; Schutz, G.; Silva, A.J. (1994). "Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein". Cell 79 (1): 59–68. doi:10.1016/0092-8674(94)90400-6. PMID 7923378.
  13. ↑ Silva, A.J.; Kogan, J.H.; Frankland, P.W.; Kida, S. (1998). "CREB and memory". Annu Rev Neurosci 21: 127–48. doi:10.1146/annurev.neuro.21.1.127.
  14. ↑ Silva, A.J.; Rosahl, T.W.; Chapman, P.F.; Marowitz, Z.; Friedman, E.; Frankland, P.W.; Cestari, V.; Cioffi, D.; Sudhof, T.C.; Bourtchuladze, R. (1996). "Impaired learning in mice with abnormal short-lived plasticity". Curr Biol 6 (11): 1509–18. doi:10.1016/s0960-9822(96)00756-7. PMID 8939606.
  15. ↑ Lee, Y-S; Silva, AJ (Feb 2009). "The molecular and cellular biology of enhanced cognition". Nat Rev Neurosci 10 (2): 126–40. doi:10.1038/nrn2572. PMID 19153576.
  16. 1 2 Ehninger, D., Li, W, Fox, K, Stryker, MP, and Silva, AJ. Reversing neurodevelopmental disorders in adults. Neuron 2008;60(6):950-60. PMCID: PMC2710296.
  17. ↑ Castren, E.; Elgersma, Y.; et al. (2012). "Treatment of neurodevelopmental disorders in adulthood". The Journal of neuroscience : the official journal of the Society for Neuroscience 32 (41): 14074–14079. doi:10.1523/jneurosci.3287-12.2012.
  18. 1 2 Costa, R.M.; Federov, N.B.; Kogan, J.H.; Murphy, G.G.; Stern, J.; Ohno, M.; Kucherlapati, R.; Jacks, T.; Silva, A.J. (2002). "Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1". Nature 415 (6871): 526–30. doi:10.1038/nature711. PMID 11793011.
  19. ↑ Kwon, C. H.; Zhu, X.; Zhang, J.; Baker, S. J. (2003). "mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo". Proc Natl Acad Sci U S A 100: 12923–12928. doi:10.1073/pnas.2132711100.
  20. ↑ Bourtchouladze, R.; Lidge, R.; Catapano, R.; Stanley, J.; Gossweiler, S.; Romashko, D.; Scott, R.; Tully, T. (2003). "A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4". Proc Natl Acad Sci U S A 100: 10518–10522. doi:10.1073/pnas.1834280100. PMC 193593. PMID 12930888.
  21. ↑ McBride, S. M.; Choi, C. H.; Wang, Y.; Liebelt, D.; Braunstein, E.; Ferreiro, D.; Sehgal, A.; Siwicki, K. K.; Dockendorff, T. C.; Nguyen, H. T.; et al. (2005). "Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome". Neuron 45: 753–764. doi:10.1016/j.neuron.2005.01.038.
  22. ↑ Fernandez, F.; Morishita, W.; Zuniga, E.; Nguyen, J.; Blank, M.; Malenka, R. C.; Garner, C. C. (2007). "Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome". Nat Neurosci 10: 411–413. doi:10.1038/nn1860. PMID 17322876.
  23. ↑ Guy, J.; Gan, J.; Selfridge, J.; Cobb, S.; Bird, A. (2007). "Reversal of neurological defects in a mouse model of Rett syndrome". Science 315: 1143–1147. doi:10.1126/science.1138389. PMID 17289941.
  24. ↑ Van Woerden, G. M.; Harris, K. D.; Hojjati, M. R.; Gustin, R. M.; Qiu, S.; de Avila Freire, R.; Jiang, Y. H.; Elgersma, Y.; Weeber, E. J. (2007). "Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation". Nat Neurosci 10: 280–282. doi:10.1038/nn1845.
  25. ↑ Ehninger, D.; Han, S.; Shilyansky, C.; Zhou, Y.; Li, W.; Kwiatkowski, D. J.; Ramesh, V.; Silva, A. J. (2008). "Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis". Nat Med 14: 843–848. doi:10.1038/nm1788. PMC 2664098. PMID 18568033.
  26. ↑ Li, W.; Cui, Y.; Kushner, S.A.; Brown, R.A.; Jentsch, J.D.; Frankland, P.W.; Cannon, T.D.; Silva, A.J. (2005). "The HMG-CoA reductase inhibitor lovastatin (U.S. Food and Drug Administration (FDA) approved) reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1". Curr Biol 15 (21): 1961–7. doi:10.1016/j.cub.2005.09.043. PMID 16271875.
  27. ↑ Cui, Y; Costa, RM; Murphy, GG; Elgersma, Y; Zhu, Y; Gutmann, DH; Parada, LF; Mody, I; Silva, AJ (2008). "Neurofibromin regulation of ERK signaling modulates GABA release and learning". Cell 135 (3): 549–560. doi:10.1016/j.cell.2008.09.060.
  28. ↑ Sebti SM, Tkalcevic GT, Jani JP: Lovastatin, a cholesterol biosynthesis inhibitor, inhibits the growth of human H-ras oncogene transformed cells in nude mice. Cancer Commun 1991; 3:141-147.
  29. ↑ Krab, L.C.; Aarsen, F.K.; Pluijm, S.M.; Bouman, M.J.; Lequin, M.; Catsman, C.E.; Arts, W.F.; Kushner, S.A.; Silva, A.J.; Moll, H.A.; Elgersma, Y. (2008). "Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial". JAMA 300 (3): 287–94. doi:10.1001/jama.300.3.287. PMC 2664742. PMID 18632543.
  30. ↑ Chabernaud, C; Mennes, M; Kardel, PG; Gaillard, WD; Kalbfleisch, ML; Vanmeter, JW; Packer, RJ; Milham, MP; Castellanos, FX; Acosta, MT (Apr 2012). "Lovastatin regulates brain spontaneous low-frequency brain activity in neurofibromatosis type 1". Neurosci Lett. 515 (1): 28–33. doi:10.1016/j.neulet.2012.03.009.
  31. ↑ Acosta, MT; Kardel, PG; Walsh, KS; Rosenbaum, KN; Gioia, GA; Packer, RJ (Oct 2011). "Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study". Pediatr Neurol 45 (4): 241–5. doi:10.1016/j.pediatrneurol.2011.06.016.
  32. ↑ Acosta, MT; Bearden, CE; Castellanos, XF; Cutting, L; Elgersma, Y; Gioia, G; Gutmann, DH; Lee, YS; Legius, E; Muenke, M; North, K; Parada, LF; Ratner, N; Hunter-Schaedle, K; Silva, AJ (2012). "The Learning Disabilities Network (LeaDNet): Using neurofibromatosis type 1 (NF1) as a paradigm for translational research". American Journal of Medical Genetics 158A (9): 2225–32. doi:10.1002/ajmg.a.35535. PMID 22821737.
  33. ↑ Gutmann, DH; Parada, LF; Silva, AJ; Ratner, N (2012). "Neurofibromatosis type 1: modeling CNS dysfunction". J Neurosci 32 (41): 14087–93. doi:10.1523/JNEUROSCI.3242-12.2012. PMID 23055477.
  34. ↑ Ehninger, D.; Han, S.; Shilyansky, C.; Zhou, Y.; Li, W.; Kwiatkowski, D.J.; Ramesh, V.; Silva, A.J. (2008). "Reversal of learning deficits in a Tsc2(+/-) mouse model of tuberous sclerosis". Nat Med 14: 843–848. doi:10.1038/nm1788. PMC 2664098. PMID 18568033.
  35. 1 2 Ehninger, D.; Sano, Y.; Dies, K.; Franz, D.; Geschwind, D.H.; Kaur, M.; Lee, Y.S.; Li, W.; Lowe, J.K.; Nakagawa, J.A.; Sahin, M.; Smith, K.; Whittemore, V.; Silva, A.J. (2012). "Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice". Molecular Psychiatry 17 (1): 62–70. doi:10.1038/mp.2010.115. PMID 21079609.
  36. ↑ Zhou, M; Li, W; Huang, S; Song, J; Kim, J Tian; Kang, E Sano; Liu, C; Balaji, J; Wu, S; Zhou, Y; Zhou, Y; Parivash, S; Ehninger, D; He, L. Song; 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. doi:10.1016/j.neuron.2012.12.033.
  37. ↑ Ehninger, D.; Li, W; Fox, K; Stryker, MP; Silva, AJ. (2008). "Reversing neurodevelopmental disorders in adults". Neuron 60 (6): 950–60. doi:10.1016/j.neuron.2008.12.007.
  38. 1 2 Frankland, P.W.; O'Brien, C.; Ohno, M.; Kirkwood, A.; Silva, A.J. (2001). "Alpha-CaMKII-dependent plasticity in the cortex is required for permanent memory". Nature 411 (6835): 309–13. doi:10.1038/35077089. PMID 11357133.
  39. 1 2 Frankland, P.W.; Bontempi, B.; Talton, L.E.; Kaczmarek, L.; Silva, A.J. (2004). "The involvement of the anterior cingulate cortex in remote contextual fear memory". Science 304 (5672): 881–3. doi:10.1126/science.1094804. PMID 15131309.
  40. ↑ Bontempi, B.; Laurent-Demir, C.; et al. (1999). "Time-dependent reorganization of brain circuitry underlying long-term memory storage". Nature 400 (6745): 671–675. doi:10.1038/23270.
  41. ↑ Frankland, P. W.; Bontempi, B. (2005). "The organization of recent and remote memories". Nat Rev Neurosci 6 (2): 119–130. doi:10.1038/nrn1607. PMID 15685217.
  42. ↑ Han, J.H.; Kushner, S.A.; Yiu, A.P.; Cole, C.J.; Matynia, A.; Brown, R.A.; Neve, R.L.; Guzowski, J.F.; Silva, A.J.; Josselyn, S.A. (2007). "Neuronal competition and selection during memory formation". Science 316 (5823): 457–60. doi:10.1126/science.1139438. PMID 17446403.
  43. ↑ Zhou, Y; Won, J.; Karlsson, M.G. Zhou; Rogerson, T; Balaji, J.; Neve, R.; Poirazi, P.; Silva, A.J. (2009). "CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala". Nature Neuroscience 12 (11): 1438–43. doi:10.1038/nn.2405. PMC 2783698. PMID 19783993.
  44. ↑ Silva, A.J.; Zhou, Y; Rogerson, T; Shobe, J; Balaji, J. (2009). "Molecular and Cellular Approaches to Memory Allocation in Neural Circuits". Science 326 (5951): 391–5. doi:10.1126/science.1174519. PMID 19833959.
  45. ↑ Szalay, A; Gray, J (2006). "2020 Computing: Science in an exponential world". Nature 440: 413–414. doi:10.1038/440413a.
  46. ↑ Silva, AJ; Müller, KR (Aug 2015). "The need for novel informatics tools for integrating and planning research in molecular and cellular cognition". Learn Mem. 22 (9): 494–8. doi:10.1101/lm.029355.112. PMID 26286658.
  47. ↑ Landreth, A; Silva, AJ (2013). "The need for research maps to navigate published work and inform experiment planning". Neuron 79 (3): 411–5. doi:10.1016/j.neuron.2013.07.024. PMID 23931992.
  48. ↑ Bickle, J. and Silva, A. (2008). Intimology and the Search for the Molecular Mechanisms of Cognitive Functions. Bickle, J. (Eds.), Oxford Handbook of Philosophy and Neuroscience. Oxford: Oxford University Press
  49. ↑ "Beckman Young Investigators Award Recipients". Arnold and Mabel Beckman Foundation. Retrieved 17 October 2014.
  50. ↑ "Senior Roche Award 2009 Press Release".

External links


This article is issued from Wikipedia - version of the Tuesday, May 03, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.