Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2012 (2012), Article ID 101542, 12 pages
http://dx.doi.org/10.1155/2012/101542
Review Article

From Abnormal Hippocampal Synaptic Plasticity in Down Syndrome Mouse Models to Cognitive Disability in Down Syndrome

Department of Anatomy, Physiology, and Genetics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA

Received 2 March 2012; Revised 2 May 2012; Accepted 7 May 2012

Academic Editor: Hansen Wang

Copyright © 2012 Nathan Cramer and Zygmunt Galdzicki. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Suri, B. D. Tompson, and L. Cornfoot, “Cranial base, maxillary and mandibular morphology in Down syndrome,” Angle Orthodontist, vol. 80, no. 5, pp. 861–869, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. R. Sureshbabu, R. Kumari, S. Ranugha, R. Sathyamoorthy, C. Udayashankar, and P. Oudeacoumar, “Phenotypic and dermatological manifestations in Down syndrome,” Dermatology Online Journal, vol. 17, no. 2, p. 3, 2011. View at Google Scholar · View at Scopus
  3. M. E. Weijerman, A. M. van Furth, M. D. van der Mooren et al., “Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome,” European Journal of Pediatrics, vol. 169, no. 10, pp. 1195–1199, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. K. H. Baek, A. Zaslavsky, R. C. Lynch et al., “Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1,” Nature, vol. 459, no. 7250, pp. 1126–1130, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. I. Khan, S. Malinge, and J. D. Crispino, “Myeloid leukemia in down syndrome,” Critical Reviews in Oncogenesis, vol. 16, no. 1-2, pp. 25–36, 2011. View at Google Scholar · View at Scopus
  6. R. S. Chapman and L. J. Hesketh, “Behavioral phenotype of individuals with Down syndrome,” Mental Retardation and Developmental Disabilities Research Reviews, vol. 6, pp. 84–95, 2000. View at Google Scholar
  7. T. F. Haydar and R. H. Reeves, “Trisomy 21 and early brain development,” Trends in Neurosciences, vol. 35, no. 2, pp. 81–91, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. T. V. P. Bliss and G. L. Collingridge, “A synaptic model of memory: long-term potentiation in the hippocampus,” Nature, vol. 361, no. 6407, pp. 31–39, 1993. View at Publisher · View at Google Scholar · View at Scopus
  9. S. B. Hofer and T. Bonhoeffer, “Dendritic spines: the stuff that memories are made of?” Current Biology, vol. 20, no. 4, pp. R157–R159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. Y. Dan and M.-M. Poo, “Spike timing-dependent plasticity: from synapse to perception,” Physiological Reviews, vol. 86, no. 3, pp. 1033–1048, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Sheng and C. C. Hoogenraad, “The postsynaptic architecture of excitatory synapses: a more quantitative view,” Annual Review of Biochemistry, vol. 76, pp. 823–847, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. J. N. Bourne and K. M. Harris, “Balancing structure and function at hippocampal dendritic spines,” Annual Review of Neuroscience, vol. 31, pp. 47–67, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Holcman and Z. Schuss, “Diffusion laws in dendritic spines,” The Journal of Mathematical Neuroscience, vol. 1, article 10, 2011. View at Google Scholar
  14. L. Nadel and V. Bohbot, “Consolidation of memory,” Hippocampus, vol. 11, pp. 56–60, 2001. View at Google Scholar
  15. E. I. Moser, E. Kropff, and M. B. Moser, “Place cells, grid cells, and the brain's spatial representation system,” Annual Review of Neuroscience, vol. 31, pp. 69–89, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. R. P. Kesner, “Behavioral functions of the CA3 subregion of the hippocampus,” Learning and Memory, vol. 14, no. 11, pp. 771–781, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. B. F. Pennington, J. Moon, J. Edgin, J. Stedron, and L. Nadel, “The Neuropsychology of Down syndrome: evidence for hippocampal dysfunction,” Child Development, vol. 74, no. 1, pp. 75–93, 2003. View at Google Scholar · View at Scopus
  18. L. Nadel, “Down's syndrome: a genetic disorder in biobehavioral perspective,” Genes, Brain and Behavior, vol. 2, no. 3, pp. 156–166, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. L. Becker, T. Mito, S. Takashima, and K. Onodera, “Growth and development of the brain in Down syndrome,” Progress in Clinical and Biological Research, vol. 373, pp. 133–152, 1991. View at Google Scholar · View at Scopus
  20. J. A. Golden and B. T. Hyman, “Development of the superior temporal neocortex is anomalous in trisomy 21,” Journal of Neuropathology and Experimental Neurology, vol. 53, no. 5, pp. 513–520, 1994. View at Google Scholar · View at Scopus
  21. B. Schmidt-Sidor, K. E. Wisniewski, T. H. Shepard, and E. A. Sersen, “Brain growth in Down syndrome subjects 15 to 22 weeks of gestational age and birth to 60 months,” Clinical Neuropathology, vol. 9, no. 4, pp. 181–190, 1990. View at Google Scholar · View at Scopus
  22. P. E. Sylvester, “The hippocampus in Down's syndrome,” Journal of Mental Deficiency Research, vol. 27, part 3, pp. 227–236, 1983. View at Google Scholar · View at Scopus
  23. A. Contestabile, T. Fila, C. Ceccarelli et al., “Cell cycle alteration and decreased cell proliferation in the hippocampal dentate gyrus and in the neocortical germinal matrix of fetuses with down syndrome and in Ts65Dn mice,” Hippocampus, vol. 17, no. 8, pp. 665–678, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Guidi, P. Bonasoni, C. Ceccarelli et al., “Neurogenesis impairment and increased cell death reduce total neuron number in the hippocampal region of fetuses with Down syndrome,” Brain Pathology, vol. 18, no. 2, pp. 180–197, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. N. Whittle, S. B. Sartori, M. Dierssen, G. Lubec, and N. Singewald, “Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development,” Pediatrics, vol. 120, no. 6, pp. e1465–e1471, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Ruediger and J. Bolz, “Neurotransmitters and the development of neuronal circuits,” Advances in Experimental Medicine and Biology, vol. 621, pp. 104–115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. K. E. Wisniewski, “Down syndrome children often have brain with maturation delay, retardation of growth, and cortical dysgenesis,” American Journal of Medical Genetics, no. 7, pp. 274–281, 1990. View at Google Scholar · View at Scopus
  28. L. E. Becker, D. L. Armstrong, and F. Chan, “Dendritic atrophy in children with Down's syndrome,” Annals of Neurology, vol. 20, no. 4, pp. 520–526, 1986. View at Google Scholar · View at Scopus
  29. S. Takashima, A. Ieshima, H. Nakamura, and L. E. Becker, “Dendrites, dementia and the Down syndrome,” Brain and Development, vol. 11, no. 2, pp. 131–133, 1989. View at Google Scholar · View at Scopus
  30. D. P. Purpura, “Normal and aberrant neuronal development in the cerebral cortex of human fetus and young infant,” UCLA Forum in Medical Sciences, no. 18, pp. 141–169, 1975. View at Google Scholar · View at Scopus
  31. M. Marin Padilla, “Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study,” Journal of Comparative Neurology, vol. 167, no. 1, pp. 63–81, 1976. View at Google Scholar · View at Scopus
  32. T. L. Petit, J. C. LeBoutillier, D. P. Alfano, and L. E. Becker, “Synaptic development in the human fetus: a morphometric analysis of normal and Down's syndrome neocortex,” Experimental Neurology, vol. 83, no. 1, pp. 13–23, 1984. View at Google Scholar · View at Scopus
  33. R. Weitzdoerfer, M. Dierssen, M. Fountoulakis, and G. Lubec, “Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure,” Journal of Neural Transmission, Supplement, no. 61, pp. 59–70, 2001. View at Google Scholar · View at Scopus
  34. S. Takashima, K. Iida, T. Mito, and M. Arima, “Dendritic and histochemical development and ageing in patients with Down's syndrome,” Journal of Intellectual Disability Research, vol. 38, part 3, pp. 265–273, 1994. View at Google Scholar · View at Scopus
  35. J. D. Pinter, S. Eliez, J. E. Schmitt, G. T. Capone, and A. L. Reiss, “Neuroanatomy of Down's syndrome: a high-resolution MRI study,” American Journal of Psychiatry, vol. 158, no. 10, pp. 1659–1665, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Śmigielska-Kuzia, L. Boćkowski, W. Sobaniec et al., “A volumetric magnetic resonance imaging study of brain structures in children with Down syndrome,” Neurologia I Neurochirurgia Polska, vol. 45, no. 4, pp. 363–369, 2011. View at Google Scholar · View at Scopus
  37. J. D. Pinter, W. E. Brown, S. Eliez, J. E. Schmitt, G. T. Capone, and A. L. Reiss, “Amygdala and hippocampal volumes in children with Down syndrome: a high-resolution MRI study,” Neurology, vol. 56, no. 7, pp. 972–974, 2001. View at Google Scholar · View at Scopus
  38. S. J. Teipel, M. B. Schapiro, G. E. Alexander et al., “Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome,” American Journal of Psychiatry, vol. 160, no. 10, pp. 1870–1878, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. J. O. Edgin, B. F. Pennington, and C. B. Mervis, “Neuropsychological components of intellectual disability: the contributions of immediate, working, and associative memory,” Journal of Intellectual Disability Research, vol. 54, no. 5, pp. 406–417, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. F. Battaglia, A. Quartarone, V. Rizzo et al., “Early impairment of synaptic plasticity in patients with Down's syndrome,” Neurobiology of Aging, vol. 29, no. 8, pp. 1272–1275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. E. A. R. Losin, S. M. Rivera, E. D. O'Hare, E. R. Sowell, and J. D. Pinter, “Abnormal fMRI activation pattern during story listening in individuals with Down syndrome,” American Journal on Intellectual and Developmental Disabilities, vol. 114, no. 5, pp. 369–380, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. L. M. Jacola, A. W. Byars, M. Chalfonte-Evans et al., “Functional magnetic resonance imaging of cognitive processing in young adults with Down syndrome,” American Journal on Intellectual and Developmental Disabilities, vol. 116, no. 5, pp. 344–359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. Z. Lengyel, E. Balogh, M. Emri et al., “Pattern of increased cerebral FDG uptake in Down syndrome patients,” Pediatric Neurology, vol. 34, no. 4, pp. 270–275, 2006. View at Publisher · View at Google Scholar · View at Scopus
  44. R. J. Siarey, J. Stoll, S. I. Rapoport, and Z. Galdzicki, “Altered long-term potentiation in the young and old Ts65Dn mouse, a model for Down Syndrome,” Neuropharmacology, vol. 36, no. 11-12, pp. 1549–1554, 1997. View at Publisher · View at Google Scholar · View at Scopus
  45. R. J. Siarey, E. J. Carlson, C. J. Epstein, A. Balbo, S. I. Rapoport, and Z. Galdzicki, “Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome,” Neuropharmacology, vol. 38, no. 12, pp. 1917–1920, 1999. View at Publisher · View at Google Scholar · View at Scopus
  46. A. O'Doherty, S. Ruf, C. Mulligan et al., “An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes,” Science, vol. 309, no. 5743, pp. 2033–2037, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. L. E. Reynolds, A. R. Watson, M. Baker et al., “Tumour angiogenesis is reduced in the Tc1 mouse model of Down' s syndrome,” Nature, vol. 465, no. 7299, pp. 813–817, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. E. Morice, L. C. Andreae, S. F. Cooke et al., “Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tcl mouse model of down syndrome,” Learning and Memory, vol. 15, no. 7, pp. 492–500, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. L. Dunlevy, M. Bennett, A. Slender et al., “Down's syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse,” Cardiovascular Research, vol. 88, no. 2, pp. 287–295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. N. P. Cramer, T. K. Best, M. Stoffel, R. J. Siarey, and Z. Galdzicki, “GABAB-GIRK2-mediated signaling in down syndrome,” Advances in Pharmacology, vol. 58, pp. 397–426, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Gotti, E. Caricati, and G. Panzica, “Alterations of brain circuits in Down syndrome murine models,” Journal of Chemical Neuroanatomy, vol. 42, no. 4, pp. 317–326, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Yu, Z. Li, Z. Jia et al., “A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions,” Human Molecular Genetics, vol. 19, no. 14, pp. 2780–2791, 2010. View at Publisher · View at Google Scholar
  53. M. T. Davisson, C. Schmidt, and E. C. Akeson, “Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome,” Progress in Clinical and Biological Research, vol. 360, pp. 263–280, 1990. View at Google Scholar · View at Scopus
  54. M. T. Davisson, C. Schmidt, R. H. Reeves et al., “Segmental trisomy as a mouse model for Down syndrome,” Progress in Clinical and Biological Research, vol. 384, pp. 117–133, 1993. View at Google Scholar · View at Scopus
  55. Z. Galdzicki and R. J. Siarey, “Understanding mental retardation in down's syndrome using trisomy 16 mouse models,” Genes, Brain and Behavior, vol. 2, no. 3, pp. 167–178, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. K. Gardiner and A. C. S. Costa, “The proteins of human chromosome 21,” American Journal of Medical Genetics, vol. 142, no. 3, pp. 196–205, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. A. C. S. Costa, “On the promise of pharmacotherapies targeted at cognitive and neurodegenerative components of down syndrome,” Developmental Neuroscience, vol. 33, no. 5, pp. 414–427, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. R. H. Reeves, N. G. Irving, T. H. Moran et al., “A mouse model for Down syndrome exhibits learning and behaviour deficits,” Nature Genetics, vol. 11, no. 2, pp. 177–184, 1995. View at Google Scholar · View at Scopus
  59. C. L. Hunter, H. A. Bimonte, and A. C. E. Granholm, “Behavioral comparison of 4 and 6 month-old Ts65Dn mice: age-related impairments in working and reference memory,” Behavioural Brain Research, vol. 138, no. 2, pp. 121–131, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Fernandez, W. Morishita, E. Zuniga et al., “Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome,” Nature Neuroscience, vol. 10, no. 4, pp. 411–413, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. N. Rueda, J. Flórez, and C. Martínez-Cué, “Effects of chronic administration of SGS-111 during adulthood and during the pre- and post-natal periods on the cognitive deficits of Ts65Dn mice, a model of Down syndrome,” Behavioural Brain Research, vol. 188, no. 2, pp. 355–367, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Blanchard, S. Bolognin, M. O. Chohan, A. Rabe, K. Iqbal, and I. Grundke-Iqbal, “Rescue of synaptic failure and alleviation of learning and memory impairments in a trisomic mouse model of down syndrome,” Journal of Neuropathology and Experimental Neurology, vol. 70, no. 12, pp. 1070–1079, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Faizi, P. L. Bader, C. Tun et al., “Comprehensive behavioral phenotyping of Ts65Dn mouse model of Down Syndrome: activation of β1-adrenergic receptor by xamoterol as a potential cognitive enhancer,” Neurobiology of Disease, vol. 43, no. 2, pp. 397–413, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Duchon, M. Raveau, C. Chevalier, V. Nalesso, A. J. Sharp, and Y. Herault, “Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling down syndrome,” Mammalian Genome, vol. 22, no. 11-12, pp. 674–684, 2011. View at Publisher · View at Google Scholar · View at Scopus
  65. H. Sago, E. J. Carlson, D. J. Smith et al., “Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 11, pp. 6256–6261, 1998. View at Publisher · View at Google Scholar · View at Scopus
  66. R. J. Siarey, A. J. Villar, C. J. Epstein, and Z. Galdzicki, “Abnormal synaptic plasticity in the Ts1Cje segmental trisomy 16 mouse model of Down syndrome,” Neuropharmacology, vol. 49, no. 1, pp. 122–128, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. P. V. Belichenko, A. M. Kleschevnikov, A. Salehi, C. J. Epstein, and W. C. Mobley, “Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships,” Journal of Comparative Neurology, vol. 504, no. 4, pp. 329–345, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. N. P. Belichenko, P. V. Belichenko, A. M. Kleschevnikov, A. Salehi, R. H. Reeves, and W. C. Mobley, “The “Down syndrome critical region” is sufficient in the mouse model to confer behavioral, neurophysiological, and synaptic phenotypes characteristic of Down syndrome,” Journal of Neuroscience, vol. 29, no. 18, pp. 5938–5948, 2009. View at Publisher · View at Google Scholar · View at Scopus
  69. L. E. Olson, R. J. Roper, C. L. Sengstaken et al., “Trisomy for the Down syndrome “critical region” is necessary but not sufficient for brain phenotypes of trisomic mice,” Human Molecular Genetics, vol. 16, no. 7, pp. 774–782, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Chakrabarti, T. K. Best, N. P. Cramer et al., “Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome,” Nature Neuroscience, vol. 13, no. 8, pp. 927–934, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. P. V. Belichenko, E. Masliah, A. M. Kleschevnikov et al., “Synaptic structural abnormalities in the Ts65Dn mouse model of Down syndrome,” Journal of Comparative Neurology, vol. 480, no. 3, pp. 281–298, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. P. V. Belichenko, A. M. Kleschevnikov, E. Masliah et al., “Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of down syndrome,” Journal of Comparative Neurology, vol. 512, no. 4, pp. 453–466, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. T. V. P. Bliss and T. Lømo, “Long lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path,” Journal of Physiology, vol. 232, no. 2, pp. 331–356, 1973. View at Google Scholar · View at Scopus
  74. G. Neves, S. F. Cooke, and T. V. P. Bliss, “Synaptic plasticity, memory and the hippocampus: a neural network approach to causality,” Nature Reviews Neuroscience, vol. 9, no. 1, pp. 65–75, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. A. M. Kleschevnicov, P. V. Belichenko, A. J. Villar, C. J. Epstein, R. C. Malenka, and W. C. Mobley, “Hippocampal long-term potentiation suppressed by increased inhibition in the Ts65Dn mouse, a genetic model of down syndrome,” Journal of Neuroscience, vol. 24, no. 37, pp. 8153–8160, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. A. C. S. Costa and M. J. Grybko, “Deficits in hippocampal CA1 LTP induced by TBS but not HFS in the Ts65Dn mouse: a model of Down syndrome,” Neuroscience Letters, vol. 382, no. 3, pp. 317–322, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. T. Yu, C. Liu, P. Belichenko et al., “Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice,” Brain Research, vol. 1366, pp. 162–171, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. J. J. Scott-McKean and A. C. S. Costa, “Exaggerated NMDA mediated LTD in a mouse model of Down syndrome and pharmacological rescuing by memantine,” Learning and Memory, vol. 18, no. 12, pp. 774–778, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. A. C. S. Costa, J. J. Scott-McKean, and M. R. Stasko, “Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test,” Neuropsychopharmacology, vol. 33, no. 7, pp. 1624–1632, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. N. Rueda, M. Llorens-Martín, J. Flórez et al., “Memantine normalizes several phenotypic features in the Ts65Dn mouse model of down syndrome,” Journal of Alzheimer's Disease, vol. 21, no. 1, pp. 277–290, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. J. Lockrow, H. Boger, H. Bimonte-Nelson, and A. C. Granholm, “Effects of long-term memantine on memory and neuropathology in Ts65Dn mice, a model for Down syndrome,” Behavioural Brain Research, vol. 221, no. 2, pp. 610–622, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. R. C. Malenka and M. F. Bear, “LTP and LTD: an embarrassment of riches,” Neuron, vol. 44, no. 1, pp. 5–21, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. G. Lynch, J. Larson, and S. Kelso, “Intracellular injections of EGTA block induction of hippocampal long-term potentiation,” Nature, vol. 305, no. 5936, pp. 719–721, 1983. View at Google Scholar · View at Scopus
  84. T. V. P. Bliss, G. L. Collingridge, and R. G. M. Morris, “Introduction. Long-term potentiation and structure of the issue,” Philosophical Transactions of the Royal Society B, vol. 358, pp. 607–611, 2003. View at Google Scholar
  85. R. C. Malenka, J. A. Kauer, D. J. Perkel et al., “An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation,” Nature, vol. 340, no. 6234, pp. 554–557, 1989. View at Google Scholar · View at Scopus
  86. R. Malinow, H. Schulman, and R. W. Tsien, “Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP,” Science, vol. 245, no. 4920, pp. 862–866, 1989. View at Google Scholar · View at Scopus
  87. D. L. Pettit, S. Perlman, and R. Malinow, “Potentiated transmission and prevention of further LTP by increased CaMKII activity in postsynaptic hippocampal slice neurons,” Science, vol. 266, no. 5192, pp. 1881–1885, 1994. View at Google Scholar · View at Scopus
  88. T. Ahmed and J. U. Frey, “Plasticity-specific phosphorylation of CaMKII, MAP-kinases and CREB during late-LTP in rat hippocampal slices in vitro,” Neuropharmacology, vol. 49, no. 4, pp. 477–492, 2005. View at Publisher · View at Google Scholar · View at Scopus
  89. Y. Lai, A. C. Nairn, and P. Greengard, “Autophosphorylation reversibly regulates the Ca2+/calmodulin-dependence of Ca2+/calmodulin-dependent protein kinase II,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 12, pp. 4253–4257, 1986. View at Google Scholar · View at Scopus
  90. R. J. Colbran and T. R. Soderling, “Calcium/calmodulin-independent autophosphorylation sites of calcium/calmodulin-dependent protein kinase II. Studies on the effect of phosphorylation of threonine 305/306 and serine 314 on calmodulin binding using synthetic peptides,” Journal of Biological Chemistry, vol. 265, no. 19, pp. 11213–11219, 1990. View at Google Scholar · View at Scopus
  91. L. Zhang, T. Kirschstein, B. Sommersberg et al., “Hippocampal synaptic metaplasticity requires inhibitory autophosphorylation of Ca2+/calmodulin-dependent kinase II,” Journal of Neuroscience, vol. 25, no. 33, pp. 7697–7707, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. G. M. van Woerden, K. D. Harris, M. R. Hojjati et al., “Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of αCaMKII inhibitory phosphorylation,” Nature Neuroscience, vol. 10, no. 3, pp. 280–282, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. R. J. Siarey, A. Kline-Burgess, M. Cho et al., “Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome,” Journal of Neurochemistry, vol. 98, no. 4, pp. 1266–1277, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Barria, V. Derkach, and T. Soderling, “Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor,” Journal of Biological Chemistry, vol. 272, no. 52, pp. 32727–32730, 1997. View at Publisher · View at Google Scholar · View at Scopus
  95. H. K. Lee, M. Barbarosie, K. Kameyama, M. F. Bear, and R. L. Huganir, “Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity,” Nature, vol. 405, no. 6789, pp. 955–959, 2000. View at Publisher · View at Google Scholar · View at Scopus
  96. V. Derkach, A. Barria, and T. R. Soderling, “Ca2+/calmodulin-kinase II enhances channel conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 6, pp. 3269–3274, 1999. View at Google Scholar · View at Scopus
  97. U. Frey, Y. Y. Huang, and E. R. Kandel, “Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons,” Science, vol. 260, no. 5114, pp. 1661–1664, 1993. View at Google Scholar · View at Scopus
  98. P. V. Nguyen, T. Abel, and E. R. Kandel, “Requirement of a critical period of transcription for induction of a late phase of LTP,” Science, vol. 265, no. 5175, pp. 1104–1107, 1994. View at Google Scholar · View at Scopus
  99. H. Matthies and K. G. Reymann, “Protein kinase A inhibitors prevent the maintenance of hippocampal long-term potentiation,” NeuroReport, vol. 4, no. 6, pp. 712–714, 1993. View at Google Scholar · View at Scopus
  100. Y. Y. Huang and E. R. Kandel, “Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization,” Learning Memory, vol. 1, no. 1, pp. 74–82, 1994. View at Google Scholar · View at Scopus
  101. T. Abel, P. V. Nguyen, M. Barad, T. A. S. Deuel, E. R. Kandel, and R. Bourtchouladze, “Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory,” Cell, vol. 88, no. 5, pp. 615–626, 1997. View at Publisher · View at Google Scholar · View at Scopus
  102. K. Kameyama, H.-K. Lee, M. F. Bear, and R. L. Huganir, “Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression,” Neuron, vol. 21, no. 5, pp. 1163–1175, 1998. View at Publisher · View at Google Scholar · View at Scopus
  103. H.-K. Lee, K. Kameyama, R. L. Huganir, and M. F. Bear, “NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus,” Neuron, vol. 21, no. 5, pp. 1151–1162, 1998. View at Publisher · View at Google Scholar · View at Scopus
  104. S. S. Kim, Y. Oh, K. C. Chung, and S. R. Seo, “Protein kinase A phosphorylates Down syndrome critical region 1 (RCAN1),” Biochemical and Biophysical Research Communications, vol. 418, no. 4, pp. 657–661, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. E. C. Beattie, R. C. Carroll, X. Yu et al., “Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD,” Nature Neuroscience, vol. 3, no. 12, pp. 1291–1300, 2000. View at Publisher · View at Google Scholar · View at Scopus
  106. D. N. Lieberman and I. Mody, “Regulation of NMDA channel function by endogenous Ca2+-dependent phosphatase,” Nature, vol. 369, no. 6477, pp. 235–239, 1994. View at Publisher · View at Google Scholar · View at Scopus
  107. J. D. Sweatt, “Mitogen-activated protein kinases in synaptic plasticity and memory,” Current Opinion in Neurobiology, vol. 14, no. 3, pp. 311–317, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Davis, P. Vanhoutte, C. Pagès, J. Caboche, and S. Laroche, “The MAPK/ERK cascade targets both Elk-1 and cAMP response element- binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo,” Journal of Neuroscience, vol. 20, no. 12, pp. 4563–4572, 2000. View at Google Scholar · View at Scopus
  109. J. D. English and J. D. Sweatt, “A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation,” Journal of Biological Chemistry, vol. 272, no. 31, pp. 19103–19106, 1997. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Goldin and M. Segal, “Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons,” European Journal of Neuroscience, vol. 17, no. 12, pp. 2529–2539, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. H. Makino and R. Malinow, “AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis,” Neuron, vol. 64, no. 3, pp. 381–390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Lisman, R. Yasuda, and S. Raghavachari, “Mechanisms of CaMKII action in long-term potentiation,” Nature Reviews Neuroscience, vol. 13, no. 3, pp. 169–182, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Matsuzaki, N. Honkura, G. C. R. Ellis-Davies, and H. Kasai, “Structural basis of long-term potentiation in single dendritic spines,” Nature, vol. 429, no. 6993, pp. 761–766, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. C. D. Harvey and K. Svoboda, “Locally dynamic synaptic learning rules in pyramidal neuron dendrites,” Nature, vol. 450, no. 7173, pp. 1195–1200, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. A. Patapoutian and L. F. Reichardt, “Trk receptors: mediators of neurotrophin action,” Current Opinion in Neurobiology, vol. 11, no. 3, pp. 272–280, 2001. View at Publisher · View at Google Scholar · View at Scopus
  116. G. M. Schratt, E. A. Nigh, W. G. Chen, L. Hu, and M. E. Greenberg, “BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development,” Journal of Neuroscience, vol. 24, no. 33, pp. 7366–7377, 2004. View at Publisher · View at Google Scholar · View at Scopus
  117. G. Dogliotti, E. Galliera, F. Licastro, and M. M. Corsi, “Age-related changes in plasma levels of BDNF in Down syndrome patients,” Immunity and Ageing, vol. 7, article 2, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. W. Pan, W. A. Banks, M. B. Fasold, J. Bluth, and A. J. Kastin, “Transport of brain-derived neurotrophic factor across the blood-brain barrier,” Neuropharmacology, vol. 37, no. 12, pp. 1553–1561, 1998. View at Publisher · View at Google Scholar · View at Scopus
  119. H. A. Bimonte-Nelson, C. L. Hunter, M. E. Nelson, and A. C. E. Granholm, “Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome,” Behavioural Brain Research, vol. 139, no. 1-2, pp. 47–57, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. P. Bianchi, E. Ciani, S. Guidi et al., “Early pharmacotherapy restores neurogenesis and cognitive performance in the Ts65Dn mouse model for down syndrome,” Journal of Neuroscience, vol. 30, no. 26, pp. 8769–8779, 2010. View at Publisher · View at Google Scholar · View at Scopus
  121. J. A. Troca-Marín, A. Alves-Sampaio, and M. L. Montesinos, “An increase in basal BDNF provokes hyperactivation of the Akt-Mammalian target of rapamycin pathway and deregulation of local dendritic translation in a mouse model of down's syndrome,” Journal of Neuroscience, vol. 31, no. 26, pp. 9445–9455, 2011. View at Publisher · View at Google Scholar · View at Scopus
  122. I. Das and R. H. Reeves, “The use of mouse models to understand and improve cognitive deficits in down syndrome,” Disease Models and Mechanisms, vol. 4, no. 5, pp. 596–606, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. C. Harashima, D. M. Jacobowitz, J. Witta et al., “Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome,” Journal of Comparative Neurology, vol. 494, no. 5, pp. 815–833, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. T. K. Best, R. J. Siarey, and Z. Galdzicki, “Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current,” Journal of Neurophysiology, vol. 97, pp. 892–900, 2007. View at Google Scholar
  125. T. K. Best, N. P. Cramer, L. Chakrabarti, T. F. Haydar, and Z. Galdzicki, “Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome,” Experimental Neurology, vol. 233, no. 2, pp. 749–757, 2012. View at Publisher · View at Google Scholar · View at Scopus
  126. A. Cooper, G. Grigoryan, L. Guy-David, M. M. Tsoory, A. Chen, and E. Reuveny, “Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 7, pp. 2642–2647, 2012. View at Publisher · View at Google Scholar · View at Scopus
  127. A. Kulik, I. Vida, Y. Fukazawa et al., “Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells,” Journal of Neuroscience, vol. 26, no. 16, pp. 4289–4297, 2006. View at Publisher · View at Google Scholar · View at Scopus
  128. T. K. Best, N. P. Cramer, L. Chakrabarti, T. F. Haydar, and Z. Galdzicki, “Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome,” Experimental Neurology, vol. 233, no. 2, pp. 749–757, 2012. View at Publisher · View at Google Scholar · View at Scopus
  129. A. M. Kleschevnikov, P. V. Belichenko, J. Gall et al., “Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome,” Neurobiology of Disease, vol. 45, no. 2, pp. 683–691, 2012. View at Publisher · View at Google Scholar · View at Scopus
  130. R. Kajiwara, F. G. Wouterlood, A. Sah, A. J. Boekel, L. T. G. Baks-Te Bulte, and M. P. Witter, “Convergence of entorhinal and CA3 inputs onto pyramidal neurons and interneurons in hippocampal area CA1—an anatomical study in the rat,” Hippocampus, vol. 18, no. 3, pp. 266–280, 2008. View at Publisher · View at Google Scholar · View at Scopus
  131. G. Maccaferri and C. J. McBain, “Passive propagation of LTD to stratum oriens-alveus inhibitory neurons modulates the temporoammonic input to the hippocampal CA1 region,” Neuron, vol. 15, no. 1, pp. 137–145, 1995. View at Google Scholar · View at Scopus
  132. C. Babiloni, G. Albertini, P. Onorati et al., “Cortical sources of EEG rhythms are abnormal in down syndrome,” Clinical Neurophysiology, vol. 121, no. 8, pp. 1205–1212, 2010. View at Publisher · View at Google Scholar · View at Scopus
  133. D. Colas, J. S. Valletta, R. Takimoto-Kimura et al., “Sleep and EEG features in genetic models of Down syndrome,” Neurobiology of Disease, vol. 30, no. 1, pp. 1–7, 2008. View at Publisher · View at Google Scholar · View at Scopus
  134. J. Braudeau, B. Delatour, A. Duchon et al., “Specific targeting of the GABA-A receptor α5 subtype by a selective inverse agonist restores cognitive deficits in Down syndrome mice,” Journal of Psychopharmacology, vol. 25, no. 8, pp. 1030–1042, 2011. View at Google Scholar
  135. J. Braudeau, L. Dauphinot, A. Duchon et al., “Chronic treatment with a promnesiant GABA-A α-selective inverse agonist increases immediate early genes expression during memory processing in mice and rectifies their expression levels in a down syndrome mouse model,” Advances in Pharmacological Sciences, vol. 2011, Article ID 153218, 2011. View at Google Scholar
  136. C. Martínez-Cué, C. Baamonde, M. Lumbreras et al., “Differential effects of environmental enrichment on behavior and learning of male and female Ts65Dn mice, a model for Down syndrome,” Behavioural Brain Research, vol. 134, no. 1-2, pp. 185–200, 2002. View at Publisher · View at Google Scholar · View at Scopus
  137. T. Begenisic, M. Spolidoro, C. Braschi et al., “Environmental enrichment decreases GABAergic inhibition and improves cognitive abilities, synaptic plasticity, and visual functions in a mouse model of Down syndrome,” Frontiers in Cellular Neuroscience, vol. 5, article 29, 2011. View at Google Scholar
  138. C. Martínez-Cué, N. Rueda, E. García, M. T. Davisson, C. Schmidt, and J. Flórez, “Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome,” Behavioural Brain Research, vol. 163, no. 2, pp. 174–185, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. L. Chakrabarti, J. Scafidi, V. Gallo, and T. F. Haydar, “Environmental enrichment rescues postnatal neurogenesis defect in the male and female Ts65Dn mouse model of down syndrome,” Developmental Neuroscience, vol. 33, no. 5, pp. 428–441, 2011. View at Publisher · View at Google Scholar · View at Scopus
  140. M. Dierssen, R. Benavides-Piccione, C. Martínez-Cué et al., “Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: effects of environmental enrichment,” Cerebral Cortex, vol. 13, no. 7, pp. 758–764, 2003. View at Publisher · View at Google Scholar · View at Scopus
  141. G. Mahoney, F. Perales, B. Wiggers, and B. Herman, “Responsive teaching: early intervention for children with Down syndrome and other disabilities,” Down's syndrome, research and practice, vol. 11, no. 1, pp. 18–28, 2006. View at Publisher · View at Google Scholar · View at Scopus
  142. C. Bonnier, “Evaluation of early stimulation programs for enhancing brain development,” Acta Paediatrica, International Journal of Paediatrics, vol. 97, no. 7, pp. 853–858, 2008. View at Publisher · View at Google Scholar · View at Scopus