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Neural Plasticity
Volume 2017, Article ID 8081758, 25 pages
https://doi.org/10.1155/2017/8081758
Review Article

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

1Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
2Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
3Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile

Correspondence should be addressed to Nibaldo C. Inestrosa; lc.cup.oib@asortsenin

Received 14 October 2016; Accepted 6 February 2017; Published 26 February 2017

Academic Editor: Tiziana Borsello

Copyright © 2017 Viviana I. Torres et al. 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. F. Ackermann, C. L. Waites, and C. C. Garner, “Presynaptic active zones in invertebrates and vertebrates,” EMBO Reports, vol. 16, no. 8, pp. 923–938, 2015. View at Publisher · View at Google Scholar · View at Scopus
  2. T. C. Südhof, “The presynaptic active zone,” Neuron, vol. 75, no. 1, pp. 11–25, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Okabe, “Molecular anatomy of the postsynaptic density,” Molecular and Cellular Neuroscience, vol. 34, no. 4, pp. 503–518, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Dani, B. Huang, J. Bergan, C. Dulac, and X. Zhuang, “Superresolution imaging of chemical synapses in the brain,” Neuron, vol. 68, no. 5, pp. 843–856, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. S. J. Sigrist and B. L. Sabatini, “Optical super-resolution microscopy in neurobiology,” Current Opinion in Neurobiology, vol. 22, no. 1, pp. 86–93, 2012. View at Publisher · View at Google Scholar
  6. R. J. Kittel and M. Heckmann, “Synaptic vesicle proteins and active zone plasticity,” Frontiers in Synaptic Neuroscience, vol. 8, article no. 8, 2016. View at Publisher · View at Google Scholar
  7. E. D. Gundelfinger and A. Fejtova, “Molecular organization and plasticity of the cytomatrix at the active zone,” Current Opinion in Neurobiology, vol. 22, no. 3, pp. 423–430, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Michel, J. A. Müller, A.-M. Oprişoreanu, and S. Schoch, “The presynaptic active zone: a dynamic scaffold that regulates synaptic efficacy,” Experimental Cell Research, vol. 335, no. 2, pp. 157–164, 2015. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Y. Zoghbi and M. F. Bear, “Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities,” Cold Spring Harbor Perspectives in Biology, vol. 4, no. 3, Article ID a009886, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. H. Y. Zoghbi, “Postnatal neurodevelopmental disorders: meeting at the synapse?” Science, vol. 302, no. 5646, pp. 826–830, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. F. Calabrese, M. A. Riva, and R. Molteni, “Synaptic alterations associated with depression and schizophrenia: potential as a therapeutic target,” Expert Opinion on Therapeutic Targets, vol. 20, no. 10, pp. 1195–1207, 2016. View at Publisher · View at Google Scholar
  12. T. C. Südhof, “Neuroligins and neurexins link synaptic function to cognitive disease,” Nature, vol. 455, no. 7215, pp. 903–911, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Bagni and W. T. Greenough, “From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome,” Nature Reviews Neuroscience, vol. 6, no. 5, pp. 376–387, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Sawa and S. H. Snyder, “Schizophrenia: diverse approaches to a complex disease,” Science, vol. 296, no. 5568, pp. 692–695, 2002. View at Publisher · View at Google Scholar · View at Scopus
  15. F. S. Price and J. A. Morris, “The genetics of bipolar disorder,” BMJ, vol. 346, article no. f530, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. D. J. Selkoe, “Alzheimer's disease is a synaptic failure,” Science, vol. 298, no. 5594, pp. 789–791, 2002. View at Publisher · View at Google Scholar · View at Scopus
  17. J. Labbadia and R. I. Morimoto, “Huntington's disease: underlying molecular mechanisms and emerging concepts,” Trends in Biochemical Sciences, vol. 38, no. 8, pp. 378–385, 2013. View at Publisher · View at Google Scholar · View at Scopus
  18. N. A. Ramakrishnan, M. J. Drescher, and D. G. Drescher, “The SNARE complex in neuronal and sensory cells,” Molecular and Cellular Neuroscience, vol. 50, no. 1, pp. 58–69, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. E. D. Gundelfinger, C. Reissner, and C. C. Garner, “Role of bassoon and piccolo in assembly and molecular organization of the active zone,” Frontiers in Synaptic Neuroscience, vol. 7, article no. 19, 2016. View at Publisher · View at Google Scholar
  20. S. Hallermann, A. Fejtova, H. Schmidt et al., “Bassoon speeds vesicle reloading at a central excitatory synapse,” Neuron, vol. 68, no. 4, pp. 710–723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Frank, M. A. Rutherford, N. Strenzke et al., “Bassoon and the synaptic ribbon organize Ca2+ channels and vesicles to add release sites and promote refilling,” Neuron, vol. 68, no. 4, pp. 724–738, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. C. L. Waites, S. A. Leal-Ortiz, T. F. M. Andlauer, S. J. Sigrist, and C. C. Garner, “Piccolo regulates the dynamic assembly of presynaptic F-actin,” Journal of Neuroscience, vol. 31, no. 40, pp. 14250–14263, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. M. P. Vawter, L. Thatcher, N. Usen, T. M. Hyde, J. E. Kleinman, and W. J. Freed, “Reduction of synapsin in the hippocampus of patients with bipolar disorder and schizophrenia,” Molecular Psychiatry, vol. 7, no. 6, pp. 571–578, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. C. C. Garcia, H. J. Blair, M. Seager et al., “Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy,” Journal of Medical Genetics, vol. 41, no. 3, pp. 183–186, 2004. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Fassio, L. Patry, S. Congia et al., “SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function,” Human Molecular Genetics, vol. 20, no. 12, pp. 2297–2307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Mirnics, F. A. Middleton, A. Marquez, D. A. Lewis, and P. Levitt, “Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex,” Neuron, vol. 28, no. 1, pp. 53–67, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. C. N. Egbujo, D. Sinclair, K. E. Borgmann-Winter, S. E. Arnold, B. I. Turetsky, and C.-G. Hahn, “Molecular evidence for decreased synaptic efficacy in the postmortem olfactory bulb of individuals with schizophrenia,” Schizophrenia Research, vol. 168, no. 1-2, article no. 6504, pp. 554–562, 2015. View at Publisher · View at Google Scholar · View at Scopus
  28. B. A. Dyck, K. J. Skoblenick, J. M. Castellano, K. Ki, N. Thomas, and R. K. Mishra, “Synapsin II knockout mice show sensorimotor gating and behavioural abnormalities similar to those in the phencyclidine-induced preclinical animal model of schizophrenia,” Schizophrenia Research, vol. 97, no. 1–3, pp. 292–293, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. B. A. Dyck, K. J. Skoblenick, J. M. Castellano, K. Ki, N. Thomas, and R. K. Mishra, “Behavioral abnormalities in synapsin II knockout mice implicate a causal factor in schizophrenia,” Synapse, vol. 63, no. 8, pp. 662–672, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. B. A. Dyck, M. G. R. Beyaert, M. A. Ferro, and R. K. Mishra, “Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: examining synapsin II in the pathophysiology of schizophrenia,” Schizophrenia Research, vol. 130, no. 1–3, pp. 250–259, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. R. Lakhan, J. Kalita, U. K. Misra, R. Kumari, and B. Mittal, “Association of intronic polymorphism rs3773364 A>G in synapsin-2 gene with idiopathic epilepsy,” Synapse, vol. 64, no. 5, pp. 403–408, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Cruceanu, E. Kutsarova, E. S. Chen et al., “DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression,” BMC Psychiatry, vol. 16, no. 1, article 286, 2016. View at Publisher · View at Google Scholar
  33. B. Porton and W. C. Wetsel, “Reduction of synapsin III in the prefrontal cortex of individuals with schizophrenia,” Schizophrenia Research, vol. 94, no. 1-3, pp. 366–370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. N. Matosin, F. Fernandez-Enright, J. S. Lum et al., “Molecular evidence of synaptic pathology in the CA1 region in schizophrenia,” NPJ Schizophrenia, vol. 2, Article ID 16022, 2016. View at Publisher · View at Google Scholar
  35. E. Scarr, L. Gray, D. Keriakous, P. J. Robinson, and B. Dean, “Increased levels of SNAP-25 and synaptophysin in the dorsolateral prefrontal cortex in bipolar I disorder,” Bipolar Disorders, vol. 8, no. 2, pp. 133–143, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. J. Blundell, P. S. Kaeser, T. C. Südhof, and C. M. Powell, “RIM1α and interacting proteins involved in presynaptic plasticity mediate prepulse inhibition and additional behaviors linked to schizophrenia,” Journal of Neuroscience, vol. 30, no. 15, pp. 5326–5333, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. J. Weidenhofer, N. A. Bowden, R. J. Scott, and P. A. Tooney, “Altered gene expression in the amygdala in schizophrenia: up-regulation of genes located in the cytomatrix active zone,” Molecular and Cellular Neuroscience, vol. 31, no. 2, pp. 243–250, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. R. A. Kumar, J. Sudi, T. D. Babatz et al., “A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism,” Journal of Medical Genetics, vol. 47, no. 2, pp. 81–90, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. Nishimura, C. L. Martin, A. Vazquez-Lopez et al., “Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways,” Human Molecular Genetics, vol. 16, no. 14, pp. 1682–1698, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. P. F. Sullivan, E. J. C. de Geus, G. Willemsen et al., “Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo,” Molecular Psychiatry, vol. 14, no. 4, pp. 359–375, 2009. View at Publisher · View at Google Scholar
  41. Z. Bochdanovits, M. Verhage, A. B. Smit et al., “Joint reanalysis of 29 correlated SNPs supports the role of PCLO/Piccolo as a causal risk factor for major depressive disorder,” Molecular Psychiatry, vol. 14, no. 7, pp. 650–652, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Minelli, C. Scassellati, C. R. Cloninger et al., “PCLO gene: its role in vulnerability to major depressive disorder,” Journal of Affective Disorders, vol. 139, no. 3, pp. 250–255, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. K. H. Choi, B. W. Higgs, J. R. Wendland, J. Song, F. J. McMahon, and M. J. Webster, “Gene expression and genetic variation data implicate PCLO in bipolar disorder,” Biological Psychiatry, vol. 69, no. 4, pp. 353–359, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. S. H. Fatemi, J. A. Earle, J. M. Stary, S. Lee, and J. Sedgewick, “Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia,” NeuroReport, vol. 12, no. 15, pp. 3257–3262, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Etain, A. Dumaine, F. Mathieu et al., “A SNAP25 promoter variant is associated with early-onset bipolar disorder and a high expression level in brain,” Molecular Psychiatry, vol. 15, no. 7, pp. 748–755, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. C. E. Young, K. Arima, J. Xie et al., “SNAP-25 deficit and hippocampal connectivity in schizophrenia,” Cerebral Cortex, vol. 8, no. 3, pp. 261–268, 1998. View at Publisher · View at Google Scholar · View at Scopus
  47. P. M. Thompson, A. C. Sower, and N. I. Perrone-Bizzozero, “Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia,” Biological Psychiatry, vol. 43, no. 4, pp. 239–243, 1998. View at Publisher · View at Google Scholar · View at Scopus
  48. C. L. Barr, Y. Feng, K. Wigg et al., “Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder,” Molecular Psychiatry, vol. 5, no. 4, pp. 405–409, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. Y. Liu, X. Dai, W. Wu et al., “The association of SNAP25 gene polymorphisms in attention deficit/hyperactivity disorder: a systematic review and meta-analysis,” Molecular Neurobiology, pp. 1–12, 2016. View at Publisher · View at Google Scholar
  50. V. A. Russell, “Neurobiology of animal models of attention-deficit hyperactivity disorder,” Journal of Neuroscience Methods, vol. 161, no. 2, pp. 185–198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. J. A. Frei and E. T. Stoeckli, “SynCAMs—from axon guidance to neurodevelopmental disorders,” Molecular and Cellular Neuroscience, 2016. View at Publisher · View at Google Scholar
  52. Y. Zhiling, E. Fujita, Y. Tanabe, T. Yamagata, T. Momoi, and M. Y. Momoi, “Mutations in the gene encoding CADM1 are associated with autism spectrum disorder,” Biochemical and Biophysical Research Communications, vol. 377, no. 3, pp. 926–929, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. E. Fujita, Y. Tanabe, B. A. Imhof, M. Y. Momoi, and T. Momoi, “Cadm1-expressing synapses on Purkinje cell dendrites are involved in mouse ultrasonic vocalization activity,” PLoS ONE, vol. 7, no. 1, Article ID e30151, 2012. View at Publisher · View at Google Scholar · View at Scopus
  54. Y. Takayanagi, E. Fujita, Z. Yu et al., “Impairment of social and emotional behaviors in Cadm1-knockout mice,” Biochemical and Biophysical Research Communications, vol. 396, no. 3, pp. 703–708, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. C. Redies, N. Hertel, and C. A. Hübner, “Cadherins and neuropsychiatric disorders,” Brain Research, vol. 1470, pp. 130–144, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. S. M. Singh, C. Castellani, and R. O'Reilly, “Autism meets schizophrenia via cadherin pathway,” Schizophrenia Research, vol. 116, no. 2-3, pp. 293–294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. A. T. Pagnamenta, H. Khan, S. Walker et al., “Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability,” Journal of Medical Genetics, vol. 48, no. 1, pp. 48–54, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. S. J. Sanders, A. G. Ercan-Sencicek, V. Hus et al., “Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism,” Neuron, vol. 70, no. 5, pp. 863–885, 2011. View at Publisher · View at Google Scholar
  59. K. Wang, H. Zhang, D. Ma et al., “Common genetic variants on 5p14.1 associate with autism spectrum disorders,” Nature, vol. 459, pp. 528–533, 2009. View at Publisher · View at Google Scholar
  60. B. St. Pourcain, K. Wang, J. T. Glessner et al., “Association between a high-risk autism locus on 5p14 and social communication spectrum phenotypes in the general population,” American Journal of Psychiatry, vol. 167, no. 11, pp. 1364–1372, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Arias-Vásquez, M. E. Altink, N. N. J. Rommelse et al., “CDH13 is associated with working memory performance in attention deficit/hyperactivity disorder,” Genes, Brain and Behavior, vol. 10, no. 8, pp. 844–851, 2011. View at Publisher · View at Google Scholar · View at Scopus
  62. Autism Genome Project Consortium, P. Szatmari, A. D. Paterson et al., “Mapping autism risk loci using genetic linkage and chromosomal rearrangements,” Nature Genetics, vol. 39, pp. 319–328, 2007. View at Publisher · View at Google Scholar
  63. H.-G. Kim, S. Kishikawa, A. W. Higgins et al., “Disruption of neurexin 1 associated with autism spectrum disorder,” The American Journal of Human Genetics, vol. 82, no. 1, pp. 199–207, 2008. View at Publisher · View at Google Scholar
  64. J. T. Glessner, K. Wang, G. Cai et al., “Autism genome-wide copy number variation reveals ubiquitin and neuronal genes,” Nature, vol. 459, pp. 569–573, 2009. View at Publisher · View at Google Scholar
  65. E. M. Morrow, S.-Y. Yoo, S. W. Flavell et al., “Identifying autism loci and genes by tracing recent shared ancestry,” Science, vol. 321, no. 5886, pp. 218–223, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. G. Kirov, D. Gumus, W. Chen et al., “Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia,” Human Molecular Genetics, vol. 17, no. 3, pp. 458–465, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Vrijenhoek, J. E. Buizer-Voskamp, I. van der Stelt et al., “Recurrent CNVs disrupt three candidate genes in schizophrenia patients,” American Journal of Human Genetics, vol. 83, no. 4, pp. 504–510, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. A. C. Need, D. Ge, M. E. Weale et al., “A genome-wide investigation of SNPs and CNVs in schizophrenia,” PLoS Genetics, vol. 5, no. 2, Article ID e1000373, 2009. View at Publisher · View at Google Scholar
  69. F. Cesca, P. Baldelli, F. Valtorta, and F. Benfenati, “The synapsins: key actors of synapse function and plasticity,” Progress in Neurobiology, vol. 91, no. 4, pp. 313–348, 2010. View at Publisher · View at Google Scholar
  70. H.-T. Kao, B. Porton, S. Hilfiker et al., “Molecular evolution of the synapsin gene family,” Journal of Experimental Zoology, vol. 285, no. 4, pp. 360–377, 1999. View at Publisher · View at Google Scholar · View at Scopus
  71. D. Gitler, Y. Xu, H.-T. Kao et al., “Molecular determinants of synapsin targeting to presynaptic terminals,” Journal of Neuroscience, vol. 24, no. 14, pp. 3711–3720, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. S. E. Kwon and E. R. Chapman, “Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons,” Neuron, vol. 70, no. 5, pp. 847–854, 2011. View at Publisher · View at Google Scholar · View at Scopus
  73. J. O. Brooks, C. E. Bearden, J. C. Hoblyn, S. A. Woodard, and T. A. Ketter, “Prefrontal and paralimbic metabolic dysregulation related to sustained attention in euthymic older adults with bipolar disorder,” Bipolar Disorders, vol. 12, no. 8, pp. 866–874, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Wang, M. Okamoto, F. Schmitz, K. Hofmann, and T. C. Südhof, “Rim is a putative rab3 effector in regulating synaptic-vesicle fusion,” Nature, vol. 388, no. 6642, pp. 593–598, 1997. View at Publisher · View at Google Scholar · View at Scopus
  75. Y. Wang and T. C. Südhof, “Genomic definition of RIM proteins: evolutionary amplification of a family of synaptic regulatory proteins,” Genomics, vol. 81, no. 2, pp. 126–137, 2003. View at Publisher · View at Google Scholar · View at Scopus
  76. P. S. Kaeser and T. C. Südhof, “RIM function in short- and long-term synaptic plasticity,” Biochemical Society Transactions, vol. 33, no. 6, pp. 1345–1349, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. Y. Takada, M. Hirano, S. Kiyonaka et al., “Rab3 interacting molecule 3 mutations associated with autism alter regulation of voltage-dependent Ca2+ channels,” Cell Calcium, vol. 58, no. 3, pp. 296–306, 2015. View at Publisher · View at Google Scholar · View at Scopus
  78. P. S. Kaeser, L. Deng, M. Fan, and T. C. Südhof, “RIM genes differentially contribute to organizing presynaptic release sites,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 29, pp. 11830–11835, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. E. Alvarez-Baron, K. Michel, T. Mittelstaedt et al., “RIM3γ and RIM4γ are key regulators of neuronal arborization,” Journal of Neuroscience, vol. 33, no. 2, pp. 824–839, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Penzes, M. E. Cahill, K. A. Jones, J.-E. Vanleeuwen, and K. M. Woolfrey, “Dendritic spine pathology in neuropsychiatric disorders,” Nature Neuroscience, vol. 14, no. 3, pp. 285–293, 2011. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Dresbach, V. Torres, N. Wittenmayer et al., “Assembly of active zone precursor vesicles: obligatory trafficking of presynaptic cytomatrix proteins Bassoon and Piccolo via A trans-Golgi compartment,” The Journal of Biological Chemistry, vol. 281, no. 9, pp. 6038–6047, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. C. Maas, V. I. Torres, W. D. Altrock et al., “Formation of Golgi-derived active zone precursor vesicles,” Journal of Neuroscience, vol. 32, no. 32, pp. 11095–11108, 2012. View at Publisher · View at Google Scholar · View at Scopus
  83. D. Wagh, R. Terry-Lorenzo, C. L. Waites et al., “Piccolo directs activity dependent F-actin assembly from presynaptic active zones via daam1,” PLoS ONE, vol. 10, no. 4, Article ID e120093, 2015. View at Publisher · View at Google Scholar · View at Scopus
  84. C. L. Waites, S. A. Leal-Ortiz, N. Okerlund et al., “Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation,” EMBO Journal, vol. 32, no. 7, pp. 954–969, 2013. View at Publisher · View at Google Scholar · View at Scopus
  85. Y. Furukawa-Hibi, A. Nitta, H. Fukumitsu et al., “Overexpression of piccolo C2A domain induces depression-like behavior in mice,” NeuroReport, vol. 21, no. 18, pp. 1177–1181, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Selak, A. V. Paternain, M. I. Aller, E. Picó, R. Rivera, and J. Lerma, “A role for SNAP25 in internalization of kainate receptors and synaptic plasticity,” Neuron, vol. 63, no. 5, p. 709, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. C. G. Lau, Y. Takayasu, A. Rodenas-Ruano et al., “SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking,” The Journal of Neuroscience, vol. 30, no. 1, pp. 242–254, 2010. View at Publisher · View at Google Scholar · View at Scopus
  88. R. Tomasoni, D. Repetto, R. Morini et al., “SNAP-25 regulates spine formation through postsynaptic binding to p140Cap,” Nature Communications, vol. 4, article 2136, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. T. Biederer, Y. Sara, M. Mozhayeva et al., “SynCAM, a synaptic adhesion molecule that drives synapse assembly,” Science, vol. 297, no. 5586, pp. 1525–1531, 2002. View at Publisher · View at Google Scholar · View at Scopus
  90. E. M. Robbins, A. J. Krupp, K. Perez de Arce et al., “SynCAM 1 adhesion dynamically regulates synapse number and impacts plasticity and learning,” Neuron, vol. 68, no. 5, pp. 894–906, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. I. H. Bekirov, L. A. Needleman, W. Zhang, and D. L. Benson, “Identification and localization of multiple classic cadherins in developing rat limbic system,” Neuroscience, vol. 115, no. 1, pp. 213–227, 2002. View at Publisher · View at Google Scholar · View at Scopus
  92. J. D. Jontes, M. R. Emond, and S. J. Smith, “In vivo trafficking and targeting of N-cadherin to nascent presynaptic terminals,” Journal of Neuroscience, vol. 24, no. 41, pp. 9027–9034, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. D. L. Benson and H. Tanaka, “N-cadherin redistribution during synaptogenesis in hippocampal neurons,” Journal of Neuroscience, vol. 18, no. 17, pp. 6892–6904, 1998. View at Google Scholar · View at Scopus
  94. S. Yamada, S. Pokutta, F. Drees, W. I. Weis, and W. J. Nelson, “Deconstructing the cadherin-catenin-actin complex,” Cell, vol. 123, no. 5, pp. 889–901, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. E. R. Graf, X. Zhang, S.-X. Jin, M. W. Linhoff, and A. M. Craig, “Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins,” Cell, vol. 119, no. 7, pp. 1013–1026, 2004. View at Publisher · View at Google Scholar · View at Scopus
  96. A. W. Püschel and H. Betz, “Neurexins are differentially expressed in the embryonic nervous system of mice,” Journal of Neuroscience, vol. 15, no. 4, pp. 2849–2856, 1995. View at Google Scholar · View at Scopus
  97. B. Ullrich, Y. A. Ushkaryov, and T. C. Südhof, “Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons,” Neuron, vol. 14, no. 3, pp. 497–507, 1995. View at Publisher · View at Google Scholar · View at Scopus
  98. K. Ichtchenko, T. Nguyen, and T. C. Südhof, “Structures, alternative splicing, and neurexin binding of multiple neuroligins,” The Journal of Biological Chemistry, vol. 271, no. 5, pp. 2676–2682, 1996. View at Publisher · View at Google Scholar · View at Scopus
  99. C. Dean, F. G. Scholl, J. Choih et al., “Neurexin mediates the assembly of presynaptic terminals,” Nature Neuroscience, vol. 6, no. 7, pp. 708–716, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. P. Scheiffele, J. Fan, J. Choih, R. Fetter, and T. Serafini, “Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons,” Cell, vol. 101, no. 6, pp. 657–669, 2000. View at Publisher · View at Google Scholar · View at Scopus
  101. A. Maximov, T. C. Südhof, and I. Bezprozvanny, “Association of neuronal calcium channels with modular adaptor proteins,” Journal of Biological Chemistry, vol. 274, no. 35, pp. 24453–24456, 1999. View at Publisher · View at Google Scholar · View at Scopus
  102. L. E. W. LaConte, V. Chavan, C. Liang et al., “CASK stabilizes neurexin and links it to liprin-α in a neuronal activity-dependent manner,” Cellular and Molecular Life Sciences, vol. 73, no. 18, pp. 3599–3621, 2016. View at Publisher · View at Google Scholar · View at Scopus
  103. J. M. Friedman, A. Baross, A. D. Delaney et al., “Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation,” The American Journal of Human Genetics, vol. 79, no. 3, pp. 500–513, 2006. View at Publisher · View at Google Scholar
  104. M. Geppert, M. Khvotchev, V. Krasnoperov et al., “Neurexin Iα is a major α-latrotoxin receptor that cooperates in α-latrotoxin action,” Journal of Biological Chemistry, vol. 273, no. 3, pp. 1705–1710, 1998. View at Publisher · View at Google Scholar · View at Scopus
  105. M. R. Etherton, K. Tabuchi, M. Sharma, J. Ko, and T. C. Südhof, “An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus,” The EMBO Journal, vol. 30, no. 14, pp. 2908–2919, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. E. S. Brodkin, “BALB/c mice: low sociability and other phenotypes that may be relevant to autism,” Behavioural Brain Research, vol. 176, no. 1, pp. 53–65, 2007. View at Publisher · View at Google Scholar · View at Scopus
  107. E. Kim and M. Sheng, “The postsynaptic density,” Current Biology, vol. 19, no. 17, pp. R723–R724, 2009. View at Publisher · View at Google Scholar
  108. X. Chen, L. Vinade, R. D. Leapman et al., “Mass of the postsynaptic density and enumeration of three key molecules,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 32, pp. 11551–11556, 2005. View at Publisher · View at Google Scholar · View at Scopus
  109. T. A. Blanpied, J. M. Kerr, and M. D. Ehlers, “Structural plasticity with preserved topology in the postsynaptic protein network,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 34, pp. 12587–12592, 2008. View at Publisher · View at Google Scholar
  110. J. F. Sturgill, P. Steiner, B. L. Czervionke, and B. L. Sabatini, “Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking,” The Journal of Neuroscience, vol. 29, no. 41, pp. 12845–12854, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Blundell, C. A. Blaiss, M. R. Etherton et al., “Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior,” The Journal of Neuroscience, vol. 30, no. 6, pp. 2115–2129, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. J. Kim, S. Jung, Y. K. Lee et al., “Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals,” Proceedings of the National Academy of Sciences, vol. 105, no. 26, pp. 9087–9092, 2008. View at Publisher · View at Google Scholar
  113. E. Tristán-Clavijo, R. J. Camacho-Garcia, E. Robles-Lanuza et al., “A truncating mutation in Alzheimer's disease inactivates neuroligin-1 synaptic function,” Neurobiology of Aging, vol. 36, no. 12, pp. 3171–3175, 2015. View at Publisher · View at Google Scholar · View at Scopus
  114. R. Dahlhaus and A. El-Husseini, “Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome,” Behavioural Brain Research, vol. 208, no. 1, pp. 96–105, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. C. Sun, M.-C. Cheng, R. Qin et al., “Identification and functional characterization of rare mutations of the neuroligin-2 gene (NLGN2) associated with schizophrenia,” Human Molecular Genetics, vol. 20, no. 15, pp. 3042–3051, 2011. View at Publisher · View at Google Scholar · View at Scopus
  116. M. Wöhr, J. L. Silverman, M. L. Scattoni et al., “Developmental delays and reduced pup ultrasonic vocalizations but normal sociability in mice lacking the postsynaptic cell adhesion protein neuroligin2,” Behavioural Brain Research, vol. 251, pp. 50–64, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. Z. Talebizadeh, D. Y. Lam, M. F. Theodoro, D. C. Bittel, G. H. Lushington, and M. G. Butler, “Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism,” Journal of medical genetics, vol. 43, no. 5, 2006. View at Publisher · View at Google Scholar · View at Scopus
  118. J. Yan, G. Oliveira, A. Coutinho et al., “Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients,” Molecular Psychiatry, vol. 10, no. 4, pp. 329–332, 2005. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Jamain, H. Quach, C. Betancur et al., “Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism,” Nature Genetics, vol. 34, no. 1, pp. 27–29, 2003. View at Publisher · View at Google Scholar · View at Scopus
  120. M. Etherton, C. Földy, M. Sharma et al., “Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 33, pp. 13764–13769, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. R. Pizzarelli and E. Cherubini, “Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism,” Frontiers in Cellular Neuroscience, vol. 7, article 85, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. F. Laumonnier, F. Bonnet-Brilhault, M. Gomot et al., “X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family,” The American Journal of Human Genetics, vol. 74, no. 3, pp. 552–557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  123. A. Lawson-Yuen, J.-S. Saldivar, S. Sommer, and J. Picker, “Familial deletion within NLGN4 associated with autism and Tourette syndrome,” European Journal of Human Genetics, vol. 16, no. 5, pp. 614–618, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. L. Shi, X. Chang, P. Zhang, M. P. Coba, W. Lu, and K. Wang, “The functional genetic link of NLGN4X knockdown and neurodevelopment in neural stem cells,” Human Molecular Genetics, vol. 22, no. 18, pp. 3749–3760, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. C. Zhang, J. M. Milunsky, S. Newton et al., “A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export,” The Journal of Neuroscience, vol. 29, no. 35, pp. 10843–10854, 2009. View at Publisher · View at Google Scholar · View at Scopus
  126. M. A. Bemben, Q. Nguyen, T. Wang, Y. Li, R. A. Nicoll, and K. W. Roche, “Autism-associated mutation inhibits protein kinase C-mediated neuroligin-4X enhancement of excitatory synapses,” Proceedings of the National Academy of Sciences, vol. 112, no. 8, pp. 2551–2556, 2015. View at Publisher · View at Google Scholar
  127. J. Tarabeux, O. Kebir, J. Gauthier et al., “Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia,” Translational Psychiatry, vol. 1, article e55, 2011. View at Publisher · View at Google Scholar · View at Scopus
  128. J. A. Saunders, V. M. Tatard-Leitman, J. Suh, E. N. Billingslea, T. P. Roberts, and S. J. Siegel, “Knockout of NMDA receptors in parvalbumin interneurons recreates autism-like phenotypes,” Autism Research, vol. 6, no. 2, pp. 69–77, 2013. View at Publisher · View at Google Scholar · View at Scopus
  129. T. Nakako, T. Murai, M. Ikejiri et al., “Effects of lurasidone on ketamine-induced joint visual attention dysfunction as a possible disease model of autism spectrum disorders in common marmosets,” Behavioural Brain Research, vol. 274, pp. 349–354, 2014. View at Publisher · View at Google Scholar · View at Scopus
  130. J. T. Noga, T. M. Hyde, M. M. Herman et al., “Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains,” Synapse, vol. 27, no. 3, pp. 168–176, 1997. View at Publisher · View at Google Scholar · View at Scopus
  131. C.-G. Hahn, H.-Y. Wang, D.-S. Cho et al., “Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia,” Nature Medicine, vol. 12, no. 7, pp. 824–828, 2006. View at Publisher · View at Google Scholar · View at Scopus
  132. S. I. Mota, I. L. Ferreira, and A. C. Rego, “Dysfunctional synapse in Alzheimer's disease—a focus on NMDA receptors,” Neuropharmacology, vol. 76, pp. 16–26, 2014. View at Publisher · View at Google Scholar · View at Scopus
  133. K. Parameshwaran, M. Dhanasekaran, and V. Suppiramaniam, “Amyloid beta peptides and glutamatergic synaptic dysregulation,” Experimental Neurology, vol. 210, no. 1, pp. 7–13, 2008. View at Publisher · View at Google Scholar · View at Scopus
  134. I. L. Ferreira, L. M. Bajouco, S. I. Mota, Y. P. Auberson, C. R. Oliveira, and A. C. Rego, “Amyloid beta peptide 1-42 disturbs intracellular calcium homeostasis through activation of GluN2B-containing N-methyl-d-aspartate receptors in cortical cultures,” Cell Calcium, vol. 51, no. 2, pp. 95–106, 2012. View at Publisher · View at Google Scholar · View at Scopus
  135. H. W. Kessels, S. Nabavi, and R. Malinow, “Metabotropic NMDA receptor function is required for β-amyloid-induced synaptic depression,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 10, pp. 4033–4038, 2013. View at Publisher · View at Google Scholar · View at Scopus
  136. C. Tackenberg, S. Grinschgl, A. Trutzel et al., “NMDA receptor subunit composition determines beta-amyloid-induced neurodegeneration and synaptic loss,” Cell Death and Disease, vol. 4, no. 4, article e608, 2013. View at Publisher · View at Google Scholar · View at Scopus
  137. A. J. Milnerwood, C. M. Gladding, M. A. Pouladi et al., “Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice,” Neuron, vol. 65, no. 2, pp. 178–190, 2010. View at Publisher · View at Google Scholar
  138. S.-I. Okamoto, M. A. Pouladi, M. Talantova et al., “Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin,” Nature Medicine, vol. 15, no. 12, pp. 1407–1413, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. A. J. Griswold, D. Ma, H. N. Cukier et al., “Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways,” Human Molecular Genetics, vol. 21, no. 15, pp. 3513–3523, 2012. View at Publisher · View at Google Scholar
  140. S. Jamain, C. Betancur, H. Quach et al., “Linkage and association of the glutamate receptor 6 gene with autism,” Molecular Psychiatry, vol. 7, no. 3, pp. 302–310, 2002. View at Publisher · View at Google Scholar · View at Scopus
  141. M. I. Aller, V. Pecoraro, A. V. Paternain, S. Canals, and J. Lerma, “Increased dosage of high-affinity kainate receptor gene grik4 alters synaptic transmission and reproduces autism spectrum disorders features,” The Journal of Neuroscience, vol. 35, no. 40, pp. 13619–13628, 2015. View at Publisher · View at Google Scholar · View at Scopus
  142. B. S. Pickard, M. P. Malloy, A. Christoforou et al., “Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder,” Molecular Psychiatry, vol. 11, no. 9, pp. 847–857, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. B. S. Pickard, H. M. Knight, R. S. Hamilton et al., “A common variant in the 3′UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 14940–14945, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Ramanathan, A. Woodroffe, P. L. Flodman et al., “A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R,” BMC Medical Genetics, vol. 5, article 10, 2004. View at Publisher · View at Google Scholar · View at Scopus
  145. I. J. Orozco, P. Koppensteiner, I. Ninan, and O. Arancio, “The schizophrenia susceptibility gene DTNBP1 modulates AMPAR synaptic transmission and plasticity in the hippocampus of juvenile DBA/2J mice,” Molecular and Cellular Neuroscience, vol. 58, pp. 76–84, 2014. View at Publisher · View at Google Scholar · View at Scopus
  146. C. Crisafulli, A. Chiesa, D. De Ronchi et al., “Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to antipsychotic treatment in patients with schizophrenia,” Neuroscience Letters, vol. 506, no. 1, pp. 170–174, 2012. View at Publisher · View at Google Scholar · View at Scopus
  147. C. Zhang, Y. Fang, and L. Xu, “Glutamate receptor 1 phosphorylation at serine 845 contributes to the therapeutic effect of olanzapine on schizophrenia-like cognitive impairments,” Schizophrenia Research, vol. 159, no. 2-3, pp. 376–384, 2014. View at Publisher · View at Google Scholar · View at Scopus
  148. A. Chiesa, C. Crisafulli, S. Porcelli et al., “Case–control association study of GRIA1, GRIA2and GRIA4polymorphisms in bipolar disorder,” International Journal of Psychiatry in Clinical Practice, vol. 16, no. 1, pp. 18–26, 2012. View at Publisher · View at Google Scholar · View at Scopus
  149. A. Chiesa, C. Crisafulli, S. Porcelli et al., “Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder,” European Archives of Psychiatry and Clinical Neuroscience, vol. 262, no. 4, pp. 305–311, 2012. View at Publisher · View at Google Scholar · View at Scopus
  150. M. Tian, Y. Zeng, Y. Hu et al., “7, 8-dihydroxyflavone induces synapse expression of AMPA GluA1 and ameliorates cognitive and spine abnormalities in a mouse model of fragile X syndrome,” Neuropharmacology, vol. 89, pp. 43–53, 2015. View at Publisher · View at Google Scholar · View at Scopus
  151. W. Guo, E. D. Polich, J. Su et al., “Fragile X proteins FMRP and FXR2P control synaptic GluA1 expression and neuronal maturation via distinct mechanisms,” Cell Reports, vol. 11, no. 10, pp. 1651–1666, 2015. View at Publisher · View at Google Scholar · View at Scopus
  152. M. Mandal, J. Wei, P. Zhong et al., “Impaired α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and function by mutant Huntingtin,” The Journal of Biological Chemistry, vol. 286, no. 39, pp. 33719–33728, 2011. View at Publisher · View at Google Scholar · View at Scopus
  153. R. J. Kelleher III, U. Geigenmüller, H. Hovhannisyan et al., “High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism,” PLOS ONE, vol. 7, no. 4, Article ID e35003, 2012. View at Publisher · View at Google Scholar · View at Scopus
  154. J. N. Lugo, G. D. Smith, E. P. Arbuckle et al., “Deletion of PTEN produces autism-like behavioral deficits and alterations in synaptic proteins,” Frontiers in Molecular Neuroscience, vol. 7, article 27, 2014. View at Publisher · View at Google Scholar
  155. Y.-W. Chen, H.-C. Lin, M.-C. Ng et al., “Activation of mGluR2/3 underlies the effects of N-acetylcystein on amygdala-associated autism-like phenotypes in a valproate-induced rat model of autism,” Frontiers in Behavioral Neuroscience, vol. 8, article 219, 2014. View at Publisher · View at Google Scholar · View at Scopus
  156. S. D'Antoni, M. Spatuzza, C. M. Bonaccorso et al., “Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism,” Neuroscience and Biobehavioral Reviews, vol. 46, no. 2, pp. 228–241, 2014. View at Publisher · View at Google Scholar · View at Scopus
  157. G. Dölen, E. Osterweil, B. S. S. Rao et al., “Correction of fragile X syndrome in mice,” Neuron, vol. 56, no. 6, pp. 955–962, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. J. A. Ronesi, K. A. Collins, S. A. Hays et al., “Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome,” Nature Neuroscience, vol. 15, no. 3, pp. 431–440, 2012. View at Publisher · View at Google Scholar · View at Scopus
  159. W. Guo, G. Molinaro, K. A. Collins et al., “Selective disruption of metabotropic glutamate receptor 5-homer interactions mimics phenotypes of fragile X syndrome in mice,” Journal of Neuroscience, vol. 36, no. 7, pp. 2131–2147, 2016. View at Publisher · View at Google Scholar · View at Scopus
  160. G. Leuba, A. Vernay, R. Kraftsik, E. Tardif, B. M. Riederer, and A. Savioz, “Pathological reorganization of NMDA receptors subunits and postsynaptic protein PSD-95 distribution in Alzheimer's disease,” Current Alzheimer Research, vol. 11, no. 1, pp. 86–96, 2014. View at Publisher · View at Google Scholar · View at Scopus
  161. C. Y. Shao, S. S. Mirra, H. B. R. Sait, T. C. Sacktor, and E. M. Sigurdsson, “Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease,” Acta Neuropathologica, vol. 122, no. 3, pp. 285–292, 2011. View at Publisher · View at Google Scholar · View at Scopus
  162. D. Yuki, Y. Sugiura, N. Zaima et al., “DHA-PC and PSD-95 decrease after loss of synaptophysin and before neuronal loss in patients with Alzheimer's disease,” Scientific Reports, vol. 4, Article ID 7130, 2014. View at Publisher · View at Google Scholar
  163. M. Feyder, R.-M. Karlsson, P. Mathur et al., “Association of mouse Dlg4 (PSD-95) gene deletion and human DLG4 gene variation with phenotypes relevant to autism spectrum disorders and Williams' syndrome,” The American Journal of Psychiatry, vol. 167, no. 12, pp. 1508–1517, 2010. View at Publisher · View at Google Scholar · View at Scopus
  164. J. Xing, H. Kimura, C. Wang et al., “Resequencing and association analysis of Six PSD-95-related genes as possible susceptibility genes for schizophrenia and autism spectrum disorders,” Scientific Reports, vol. 6, article 27491, 2016. View at Publisher · View at Google Scholar
  165. V. S. Catts, D. S. Derminio, C. Hahn, and C. S. Weickert, “Postsynaptic density levels of the NMDA receptor NR1 subunit and PSD-95 protein in prefrontal cortex from people with schizophrenia,” npj Schizophrenia, vol. 1, p. 15037, 2015. View at Publisher · View at Google Scholar
  166. R. P. Murmu, W. Li, Z. Szepesi, and J.-Y. Li, “Altered sensory experience exacerbates stable dendritic spine and synapse loss in a mouse model of huntington’s disease,” Journal of Neuroscience, vol. 35, no. 1, pp. 287–298, 2015. View at Publisher · View at Google Scholar · View at Scopus
  167. C. M. Gladding, J. Fan, L. Y. J. Zhang et al., “Alterations in STriatal-Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model,” Journal of Neurochemistry, vol. 130, no. 1, pp. 145–159, 2014. View at Publisher · View at Google Scholar · View at Scopus
  168. G. A. Smith, E. M. Rocha, J. R. McLean et al., “Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse model of Huntington's disease,” Human Molecular Genetics, vol. 23, no. 17, Article ID ddu166, pp. 4510–4527, 2014. View at Publisher · View at Google Scholar · View at Scopus
  169. P. K. Todd, K. J. Mack, and J. S. Malter, “The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 2, pp. 14374–14378, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. N.-P. Tsai, J. R. Wilkerson, W. Guo et al., “Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95,” Cell, vol. 151, no. 7, pp. 1581–1594, 2012. View at Publisher · View at Google Scholar · View at Scopus
  171. D. D. Krueger, E. K. Osterweil, S. P. Chen, L. D. Tye, and M. F. Bear, “Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 6, pp. 2587–2592, 2011. View at Publisher · View at Google Scholar · View at Scopus
  172. J. Arsenault, S. Gholizadeh, Y. Niibori et al., “FMRP expression levels in mouse central nervous system neurons determine behavioral phenotype,” Human Gene Therapy, vol. 27, no. 12, pp. 982–996, 2016. View at Publisher · View at Google Scholar
  173. R. M. Gandhi, C. S. Kogan, C. Messier, and L. S. Macleod, “Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome,” NeuroReport, vol. 25, no. 4, pp. 255–261, 2014. View at Publisher · View at Google Scholar · View at Scopus
  174. D. Sato, A. C. Lionel, C. S. Leblond et al., “SHANK1 deletions in males with autism spectrum disorder,” The American Journal of Human Genetics, vol. 90, no. 5, pp. 879–887, 2012. View at Publisher · View at Google Scholar
  175. A. Y. Hung, K. Futai, C. Sala et al., “Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1,” The Journal of Neuroscience, vol. 28, no. 7, pp. 1697–1708, 2008. View at Publisher · View at Google Scholar · View at Scopus
  176. M. Wöhr, F. I. Roullet, A. Y. Hung, M. Sheng, and J. N. Crawley, “Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior,” PLoS ONE, vol. 6, no. 6, Article ID e20631, 2011. View at Publisher · View at Google Scholar · View at Scopus
  177. L. Lennertz, M. Wagner, W. Wölwer et al., “A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis,” European Archives of Psychiatry and Clinical Neuroscience, vol. 262, no. 2, pp. 117–124, 2012. View at Publisher · View at Google Scholar
  178. M. Fromer, A. J. Pocklington, D. H. Kavanagh et al., “De novo mutations in schizophrenia implicate synaptic networks,” Nature, vol. 506, no. 7487, pp. 179–184, 2014. View at Publisher · View at Google Scholar
  179. S. Berkel, C. R. Marshall, B. Weiss et al., “Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation,” Nature Genetics, vol. 42, no. 6, pp. 489–491, 2010. View at Publisher · View at Google Scholar · View at Scopus
  180. C. S. Leblond, J. Heinrich, R. Delorme et al., “Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders,” PLoS Genetics, vol. 8, no. 2, Article ID e1002521, 2012. View at Publisher · View at Google Scholar
  181. M. J. Schmeisser, E. Ey, S. Wegener et al., “Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2,” Nature, vol. 486, no. 7402, pp. 256–260, 2012. View at Publisher · View at Google Scholar · View at Scopus
  182. H. Won, H.-R. Lee, H. Y. Gee et al., “Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function,” Nature, vol. 486, no. 7402, pp. 261–265, 2012. View at Publisher · View at Google Scholar · View at Scopus
  183. B. Chilian, H. Abdollahpour, T. Bierhals et al., “Dysfunction of SHANK2 and CHRNA7 in a patient with intellectual disability and language impairment supports genetic epistasis of the two loci,” Clinical Genetics, vol. 84, no. 6, pp. 560–565, 2013. View at Publisher · View at Google Scholar · View at Scopus
  184. S. Peykov, S. Berkel, M. Schoen et al., “Identification and functional characterization of rare SHANK2 variants in schizophrenia,” Molecular Psychiatry, vol. 20, no. 12, pp. 1489–1498, 2015. View at Publisher · View at Google Scholar · View at Scopus
  185. S. Peykov, S. Berkel, F. Degenhardt, M. Rietschel, M. M. Nöthen, and G. A. Rappold, “Rare SHANK2 variants in schizophrenia,” Molecular Psychiatry, vol. 20, no. 12, pp. 1487–1488, 2015. View at Publisher · View at Google Scholar · View at Scopus
  186. C. Betancur and J. D. Buxbaum, “SHANK3 haploinsufficiency: a 'common' but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders,” Molecular Autism, vol. 4, article 17, 2013. View at Publisher · View at Google Scholar · View at Scopus
  187. C. M. Durand, J. Perroy, F. Loll et al., “SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism,” Molecular Psychiatry, vol. 17, no. 1, pp. 71–84, 2012. View at Publisher · View at Google Scholar · View at Scopus
  188. M. Yang, O. Bozdagi, M. L. Scattoni et al., “Reduced excitatory neurotransmission and mild Autism-Relevant phenotypes in adolescent SHANK3 null mutant mice,” Journal of Neuroscience, vol. 32, no. 19, pp. 6525–6541, 2012. View at Publisher · View at Google Scholar · View at Scopus
  189. X. Wang, P. A. McCoy, R. M. Rodriguiz et al., “Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3,” Human Molecular Genetics, vol. 20, no. 15, pp. 3093–3108, 2011. View at Publisher · View at Google Scholar · View at Scopus
  190. J. Peça, C. Feliciano, J. T. Ting et al., “Shank3 mutant mice display autistic-like behaviours and striatal dysfunction,” Nature, vol. 472, no. 7344, pp. 437–442, 2011. View at Publisher · View at Google Scholar · View at Scopus
  191. M. Kouser, H. E. Speed, C. M. Dewey et al., “Loss of predominant shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission,” Journal of Neuroscience, vol. 33, no. 47, pp. 18448–18468, 2013. View at Publisher · View at Google Scholar · View at Scopus
  192. J. Lee, C. Chung, S. Ha et al., “Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit,” Frontiers in Cellular Neuroscience, vol. 9, article 94, 2015. View at Publisher · View at Google Scholar · View at Scopus
  193. M. H. Arons, K. Lee, C. J. Thynne et al., “Shank3 is part of a zinc-sensitive signaling system that regulates excitatory synaptic strength,” The Journal of Neuroscience, vol. 36, no. 35, pp. 9124–9134, 2016. View at Publisher · View at Google Scholar
  194. K. Phelan and H. E. McDermid, “The 22q13.3 deletion syndrome (Phelan-McDermid syndrome),” Molecular Syndromology, vol. 2, no. 3–5, pp. 186–201, 2012. View at Publisher · View at Google Scholar · View at Scopus
  195. D. Misceo, O. K. Rødningen, T. Barøy et al., “A translocation between Xq21.33 and 22q13.33 causes an intragenic SHANK3 deletion in a woman with Phelan-McDermid syndrome and hypergonadotropic hypogonadism,” American Journal of Medical Genetics, Part A, vol. 155, no. 2, pp. 403–408, 2011. View at Publisher · View at Google Scholar · View at Scopus
  196. C. S. Leblond, C. Nava, A. Polge et al., “Meta-analysis of SHANK mutations in autism spectrum disorders: a gradient of severity in cognitive impairments,” PLoS Genetics, vol. 10, no. 9, Article ID e1004580, 2014. View at Publisher · View at Google Scholar
  197. J. Gauthier, N. Champagne, R. G. Lafrenière et al., “De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia,” Proceedings of the National Academy of Sciences, vol. 107, no. 17, pp. 7863–7868, 2010. View at Publisher · View at Google Scholar
  198. K. D. Lominac, E. B. Oleson, M. Pava et al., “Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function,” Journal of Neuroscience, vol. 25, no. 50, pp. 11586–11594, 2005. View at Publisher · View at Google Scholar · View at Scopus
  199. D. F. Levinson, P. Holmans, R. E. Straub et al., “Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q, 6q, 10p, and 13q: schizophrenia linkage collaborative group III,” American Journal of Human Genetics, vol. 67, no. 3, pp. 652–663, 2000. View at Publisher · View at Google Scholar · View at Scopus
  200. H. M. D. Gurling, G. Kalsi, J. Brynjolfson et al., “Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23,” American Journal of Human Genetics, vol. 68, no. 3, pp. 661–673, 2001. View at Publisher · View at Google Scholar · View at Scopus
  201. T. Paunio, J. Ekelund, T. Varilo et al., “Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q,” Human Molecular Genetics, vol. 10, no. 26, pp. 3037–3048, 2001. View at Publisher · View at Google Scholar · View at Scopus
  202. I. Spellmann, D. Rujescu, R. Musil et al., “Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients,” Journal of Psychiatric Research, vol. 45, no. 2, pp. 234–241, 2011. View at Publisher · View at Google Scholar · View at Scopus
  203. X. Guo, P. J. Hamilton, N. J. Reish, J. D. Sweatt, C. A. Miller, and G. Rumbaugh, “Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of schizophrenia,” Neuropsychopharmacology, vol. 34, no. 7, pp. 1659–1672, 2009. View at Publisher · View at Google Scholar · View at Scopus
  204. L. N. van de Lagemaat and S. G. N. Grant, “Genome variation and complexity in the autism spectrum,” Neuron, vol. 67, no. 1, pp. 8–10, 2010. View at Publisher · View at Google Scholar · View at Scopus
  205. H. Won, W. Mah, and E. Kim, “Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses,” Frontiers in Molecular Neuroscience, vol. 6, article 19, 2013. View at Publisher · View at Google Scholar · View at Scopus
  206. M. J. Parker, A. E. Fryer, D. J. Shears et al., “De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability,” American Journal of Medical Genetics Part A, vol. 167, no. 10, pp. 2231–2237, 2015. View at Publisher · View at Google Scholar · View at Scopus
  207. A. C. Lionel, A. K. Vaags, D. Sato et al., “Rare exonic deletions implicate the synaptic organizer gephyrin (GPHN) in risk for autism, schizophrenia and seizures,” Human Molecular Genetics, vol. 22, no. 10, pp. 2055–2066, 2013. View at Publisher · View at Google Scholar · View at Scopus
  208. B. Dejanovic, D. Lal, C. B. Catarino et al., “Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy,” Neurobiology of Disease, vol. 67, pp. 88–96, 2014. View at Publisher · View at Google Scholar · View at Scopus
  209. D. St Clair, D. Blackwood, W. Muir et al., “Association within a family of a balanced autosomal translocation with major mental illness,” The Lancet, vol. 336, no. 8706, pp. 13–16, 1990. View at Publisher · View at Google Scholar · View at Scopus
  210. D. H. R. Blackwood, A. Fordyce, M. T. Walker, D. M. St Clair, D. J. Porteous, and W. J. Muir, “Schizophrenia and affective disorders—cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family,” American Journal of Human Genetics, vol. 69, no. 2, pp. 428–433, 2001. View at Publisher · View at Google Scholar · View at Scopus
  211. M. Kvajo, H. McKellar, P. A. Arguello et al., “A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 19, pp. 7076–7081, 2008. View at Publisher · View at Google Scholar · View at Scopus
  212. S. R. Leliveld, V. Bader, P. Hendriks et al., “Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease,” Journal of Neuroscience, vol. 28, no. 15, pp. 3839–3845, 2008. View at Publisher · View at Google Scholar · View at Scopus
  213. J.-F. Sauer, M. Strüber, and M. Bartos, “Impaired fast-spiking interneuron function in a genetic mouse model of depression,” eLife, vol. 2015, no. 4, Article ID e04979, 2015. View at Publisher · View at Google Scholar · View at Scopus
  214. H. Kilpinen, T. Ylisaukko-Oja, W. Hennah et al., “Association of DISC1 with autism and Asperger syndrome,” Molecular Psychiatry, vol. 13, no. 2, pp. 187–196, 2008. View at Publisher · View at Google Scholar · View at Scopus
  215. N. Shahani, S. Seshadri, H. Jaaro-Peled et al., “DISC1 regulates trafficking and processing of APP and Aβ generation,” Molecular Psychiatry, vol. 20, no. 7, pp. 874–879, 2015. View at Publisher · View at Google Scholar · View at Scopus
  216. M. A. Bemben, S. L. Shipman, R. A. Nicoll, and K. W. Roche, “The cellular and molecular landscape of neuroligins,” Trends in Neurosciences, vol. 38, no. 8, pp. 496–505, 2015. View at Publisher · View at Google Scholar · View at Scopus
  217. J.-Y. Song, K. Ichtchenko, T. C. Südhof, and N. Brose, “Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 3, pp. 1100–1105, 1999. View at Publisher · View at Google Scholar · View at Scopus
  218. E. C. Budreck and P. Scheiffele, “Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses,” European Journal of Neuroscience, vol. 26, no. 7, pp. 1738–1748, 2007. View at Publisher · View at Google Scholar · View at Scopus
  219. M. Hoon, T. Soykan, B. Falkenburger et al., “Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 7, pp. 3053–3058, 2011. View at Publisher · View at Google Scholar · View at Scopus
  220. A. Poulopoulos, G. Aramuni, G. Meyer et al., “Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin,” Neuron, vol. 63, no. 5, pp. 628–642, 2009. View at Publisher · View at Google Scholar · View at Scopus
  221. N. Dong, J. Qi, and G. Chen, “Molecular reconstitution of functional GABAergic synapses with expression of neuroligin-2 and GABAA receptors,” Molecular and Cellular Neuroscience, vol. 35, no. 1, pp. 14–23, 2007. View at Publisher · View at Google Scholar · View at Scopus
  222. T. Dolique, A. Favereaux, O. Roca-Lapirot et al., “Unexpected association of the ‘inhibitory’ neuroligin 2 with excitatory PSD95 in neuropathic pain,” Pain, vol. 154, no. 11, pp. 2529–2546, 2013. View at Publisher · View at Google Scholar · View at Scopus
  223. I. A. Sindi, R. K. Tannenberg, and P. R. Dodd, “A role for the neurexin-neuroligin complex in Alzheimer's disease,” Neurobiology of Aging, vol. 35, no. 4, pp. 746–756, 2014. View at Publisher · View at Google Scholar · View at Scopus
  224. M. C. Dinamarca, J. A. Ríos, and N. C. Inestrosa, “Postsynaptic receptors for amyloid-β oligomers as mediators of neuronal damage in Alzheimer's disease,” Frontiers in Physiology, vol. 3, article 464, 2012. View at Publisher · View at Google Scholar · View at Scopus
  225. M. C. Dinamarca, M. Di Luca, J. A. Godoy, and N. C. Inestrosa, “The soluble extracellular fragment of neuroligin-1 targets Aβ oligomers to the postsynaptic region of excitatory synapses,” Biochemical and Biophysical Research Communications, vol. 466, no. 1, Article ID 34480, pp. 66–71, 2015. View at Publisher · View at Google Scholar · View at Scopus
  226. M. C. Dinamarca, D. Weinstein, O. Monasterio, and N. C. Inestrosa, “The synaptic protein neuroligin-1 interacts with the amyloid β-peptide. is there a role in Alzheimer's disease?” Biochemistry, vol. 50, no. 38, pp. 8127–8137, 2011. View at Publisher · View at Google Scholar · View at Scopus
  227. B. Bie, J. Wu, H. Yang, J. J. Xu, D. L. Brown, and M. Naguib, “Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency,” Nature Neuroscience, vol. 17, no. 2, pp. 223–231, 2014. View at Publisher · View at Google Scholar · View at Scopus
  228. H. Malkki, “Synaptic scaffolding protein neuroligin 1 links amyloid deposition, neuroinflammation and impaired memory,” Nature Reviews Neurology, vol. 10, no. 3, article no. 122, 2014. View at Publisher · View at Google Scholar · View at Scopus
  229. S. K. Singh, J. A. Stogsdill, N. S. Pulimood et al., “Astrocytes assemble thalamocortical synapses by bridging NRX1α and NL1 via hevin,” Cell, vol. 164, no. 1-2, pp. 183–196, 2016. View at Publisher · View at Google Scholar · View at Scopus
  230. J. Blundell, K. Tabuchi, M. F. Bolliger et al., “Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2,” Genes, Brain and Behavior, vol. 8, no. 1, pp. 114–126, 2009. View at Publisher · View at Google Scholar · View at Scopus
  231. O. Babaev, P. Botta, E. Meyer et al., “Neuroligin 2 deletion alters inhibitory synapse function and anxiety-associated neuronal activation in the amygdala,” Neuropharmacology, vol. 100, pp. 56–65, 2016. View at Publisher · View at Google Scholar · View at Scopus
  232. C. Kohl, O. Riccio, J. Grosse et al., “Hippocampal neuroligin-2 overexpression leads to reduced aggression and inhibited novelty reactivity in rats,” PLoS ONE, vol. 8, no. 2, Article ID e56871, 2013. View at Publisher · View at Google Scholar · View at Scopus
  233. R. M. Hines, L. Wu, D. J. Hines et al., “Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression,” The Journal of Neuroscience, vol. 28, no. 24, pp. 6055–6067, 2008. View at Publisher · View at Google Scholar · View at Scopus
  234. K. Moriyoshi, M. Masu, T. Ishii, R. Shigemoto, N. Mizuno, and S. Nakanishi, “Molecular cloning and characterization of the rat NMDA receptor,” Nature, vol. 354, no. 6348, pp. 31–37, 1991. View at Publisher · View at Google Scholar · View at Scopus
  235. M. L. Carlsson, “Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate—serotonin interactions for pharmacotherapy,” Journal of Neural Transmission, vol. 105, no. 4-5, pp. 525–535, 1998. View at Publisher · View at Google Scholar · View at Scopus
  236. D. J. Posey, D. L. Kem, N. B. Swiezy, T. L. Sweeten, R. E. Wiegand, and C. J. McDougle, “A pilot study of D-cycloserine in subjects with autistic disorder,” The American Journal of Psychiatry, vol. 161, no. 11, pp. 2115–2117, 2004. View at Publisher · View at Google Scholar · View at Scopus
  237. H. Stefansson, E. Sigurdsson, V. Steinthorsdottir et al., “Neuregulin 1 and susceptibility to schizophrenia,” The American Journal of Human Genetics, vol. 71, no. 4, pp. 877–892, 2002. View at Publisher · View at Google Scholar
  238. Y. Liu, P. W. Tak, M. Aarts et al., “NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo,” Journal of Neuroscience, vol. 27, no. 11, pp. 2846–2857, 2007. View at Publisher · View at Google Scholar · View at Scopus
  239. M. Espinoza-Moraga, J. Caballero, F. Gaube, T. Winckler, and L. S. Santos, “1-Benzyl-1,2,3,4-tetrahydro-β-carboline as channel blocker of N-methyl-D-aspartate receptors,” Chemical Biology and Drug Design, vol. 79, no. 4, pp. 594–599, 2012. View at Publisher · View at Google Scholar · View at Scopus
  240. G. N. Woodruff, A. C. Foster, R. Gill et al., “The interaction between MK-801 and receptors for N-methyl-D-aspartate: functional consequences,” Neuropharmacology, vol. 26, pp. 903–909, 1987. View at Google Scholar
  241. S. A. Lipton, “Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurologic disorders,” Journal of Alzheimer's Disease, vol. 6, pp. S61–S74, 2004. View at Google Scholar · View at Scopus
  242. M. Rapoport, H. N. Dawson, L. I. Binder, M. P. Vitek, and A. Ferreira, “Tau is essential to β-amyloid-induced neurotoxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 9, pp. 6364–6369, 2002. View at Publisher · View at Google Scholar
  243. J. Wu, Q. Li, and I. Bezprozvanny, “Evaluation of Dimebon in cellular model of Huntington's disease,” Molecular Neurodegeneration, vol. 3, no. 1, article 15, 2008. View at Publisher · View at Google Scholar
  244. J. Palacios-Filardo, M. I. Aller, and J. Lerma, “Synaptic targeting of kainate receptors,” Cerebral Cortex, vol. 26, no. 4, pp. 1464–1472, 2016. View at Publisher · View at Google Scholar · View at Scopus
  245. J. C. Hammond, J. H. Meador-Woodruff, V. Haroutunian, and R. E. McCullumsmith, “Ampa receptor subunit expression in the endoplasmic reticulum in frontal cortex of elderly patients with schizophrenia,” PLoS ONE, vol. 7, no. 6, Article ID e39190, 2012. View at Publisher · View at Google Scholar · View at Scopus
  246. H.-C. Kornau, L. T. Schenker, M. B. Kennedy, and P. H. Seeburg, “Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95,” Science, vol. 269, no. 5231, pp. 1737–1740, 1995. View at Publisher · View at Google Scholar · View at Scopus
  247. E. Schnell, M. Sizemore, S. Karimzadegan, L. Chen, D. S. Bredt, and R. A. Nicoll, “Direct interactions between PSD-95 and stargazin control synaptic AMPA receptor number,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 21, pp. 13902–13907, 2002. View at Publisher · View at Google Scholar · View at Scopus
  248. J. H. Kim, D. Liao, L.-F. Lau, and R. L. Huganir, “SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family,” Neuron, vol. 20, no. 4, pp. 683–691, 1998. View at Publisher · View at Google Scholar · View at Scopus
  249. D. Vallejo, J. F. Codocedo, and N. C. Inestrosa, “Posttranslational modifications regulate the postsynaptic localization of PSD-95,” Molecular Neurobiology, 2016. View at Publisher · View at Google Scholar · View at Scopus
  250. E. Pham, L. Crews, K. Ubhi et al., “Progressive accumulation of amyloid-β oligomers in Alzheimer's disease and in amyloid precursor protein transgenic mice is accompanied by selective alterations in synaptic scaffold proteins,” FEBS Journal, vol. 277, no. 14, pp. 3051–3067, 2010. View at Publisher · View at Google Scholar · View at Scopus
  251. P. N. Lacor, M. C. Buniel, L. Chang et al., “Synaptic targeting by Alzheimer's-related amyloid β oligomers,” The Journal of Neuroscience, vol. 24, no. 45, pp. 10191–10200, 2004. View at Publisher · View at Google Scholar
  252. F. Roselli, M. Tirard, J. Lu et al., “Soluble β-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses,” Journal of Neuroscience, vol. 25, no. 48, pp. 11061–11070, 2005. View at Publisher · View at Google Scholar · View at Scopus
  253. W. Cerpa, G. G. Farías, J. A. Godoy, M. Fuenzalida, C. Bonansco, and N. C. Inestrosa, “Wnt-5a occludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons,” Molecular Neurodegeneration, vol. 5, no. 1, article 3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  254. J. F. Codocedo, C. Montecinos-Oliva, and N. C. Inestrosa, “Wnt-related synGAP1 is a neuroprotective factor of glutamatergic synapses against Aβ oligomers,” Frontiers in Cellular Neuroscience, vol. 9, 2015. View at Publisher · View at Google Scholar · View at Scopus
  255. F. Zalfa, B. Eleuteri, K. S. Dickson et al., “A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability,” Nature Neuroscience, vol. 10, no. 5, pp. 578–587, 2007. View at Publisher · View at Google Scholar · View at Scopus
  256. M. F. Ifrim, K. R. Williams, and G. J. Bassell, “Single-molecule imaging of PSD-95 mRNA translation in dendrites and its dysregulation in a mouse model of fragile X syndrome,” Journal of Neuroscience, vol. 35, no. 18, pp. 7116–7130, 2015. View at Publisher · View at Google Scholar · View at Scopus
  257. J. Schütt, K. Falley, D. Richter, H.-J. Kreienkamp, and S. Kindler, “Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities,” Journal of Biological Chemistry, vol. 284, no. 38, pp. 25479–25487, 2009. View at Publisher · View at Google Scholar · View at Scopus
  258. P. H. Frederikse, A. Nandanoor, and C. Kasinathan, “Fragile X syndrome FMRP Co-localizes with regulatory targets PSD-95, GABA Receptors, CaMKIIα, and mGluR5 at fiber cell membranes in the eye lens,” Neurochemical Research, vol. 40, no. 11, pp. 2167–2176, 2015. View at Publisher · View at Google Scholar · View at Scopus
  259. C. Sala, V. Piëch, N. R. Wilson, M. Passafaro, G. Liu, and M. Sheng, “Regulation of dendritic spine morphology and synaptic function by Shank and Homer,” Neuron, vol. 31, no. 1, pp. 115–130, 2001. View at Publisher · View at Google Scholar · View at Scopus
  260. A. M. Grabrucker, M. J. Schmeisser, M. Schoen, and T. M. Boeckers, “Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies,” Trends in Cell Biology, vol. 21, no. 10, pp. 594–603, 2011. View at Publisher · View at Google Scholar · View at Scopus
  261. H.-J. Kreienkamp, “Scaffolding proteins at the postsynaptic density: shank as the architectural framework,” in Protein-Protein Interactions as New Drug Targets, vol. 186 of Handbook of Experimental Pharmacology, pp. 365–380, Springer, Berlin, Germany, 2008. View at Publisher · View at Google Scholar
  262. G. Meyer, F. Varoqueaux, A. Neeb, M. Oschlies, and N. Brose, “The complexity of PDZ domain-mediated interactions at glutamatergic synapses: a case study on neuroligin,” Neuropharmacology, vol. 47, no. 5, pp. 724–733, 2004. View at Publisher · View at Google Scholar · View at Scopus
  263. A. Guilmatre, G. Huguet, R. Delorme, and T. Bourgeron, “The emerging role of SHANK genes in neuropsychiatric disorders,” Developmental Neurobiology, vol. 74, no. 2, pp. 113–122, 2014. View at Publisher · View at Google Scholar · View at Scopus
  264. J. L. Silverman, S. M. Turner, C. L. Barkan et al., “Sociability and motor functions in Shank1 mutant mice,” Brain Research, vol. 1380, pp. 120–137, 2011. View at Publisher · View at Google Scholar · View at Scopus
  265. L. T. Curtis and K. Patel, “Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): a review,” Journal of Alternative and Complementary Medicine, vol. 14, pp. 79–85, 2008. View at Publisher · View at Google Scholar · View at Scopus
  266. H. Yasuda, K. Yoshida, Y. Yasuda, and T. Tsutsui, “Infantile zinc deficiency: association with autism spectrum disorders,” Scientific Reports, vol. 1, article 129, 2011. View at Publisher · View at Google Scholar · View at Scopus
  267. G. M. Hayes, P. E. Carrigan, and L. J. Miller, “Serine-arginine protein kinase 1 overexpression is associated with tumorigenic imbalance in mitogen-activated protein kinase pathways in breast, colonic, and pancreatic carcinomas,” Cancer Research, vol. 67, no. 5, pp. 2072–2080, 2007. View at Publisher · View at Google Scholar · View at Scopus
  268. P. R. Brakeman, A. A. Lanahan, R. O'Brien et al., “Homer: a protein that selectively binds metabotropic glutamate receptors,” Nature, vol. 386, no. 6622, pp. 284–288, 1997. View at Publisher · View at Google Scholar · View at Scopus
  269. J. C. Tu, B. Xiao, J. P. Yuan et al., “Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors,” Neuron, vol. 21, no. 4, pp. 717–726, 1998. View at Publisher · View at Google Scholar · View at Scopus
  270. S.-Y. Hwang, J. Wei, J. H. Westhoff et al., “Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling,” Cell Calcium, vol. 34, no. 2, pp. 177–184, 2003. View at Publisher · View at Google Scholar · View at Scopus
  271. J. P. Yuan, K. Kiselyov, D. M. Shin et al., “Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors,” Cell, vol. 114, no. 6, pp. 777–789, 2003. View at Publisher · View at Google Scholar · View at Scopus
  272. J. C. Tu, B. Xiao, S. Naisbitt et al., “Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins,” Neuron, vol. 23, no. 3, pp. 583–592, 1999. View at Publisher · View at Google Scholar · View at Scopus
  273. Y. Shiraishi-Yamaguchi and T. Furuichi, “The Homer family proteins,” Genome Biology, vol. 8, article 206, 2007. View at Publisher · View at Google Scholar · View at Scopus
  274. S. Tekin and J. L. Cummings, “Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update,” Journal of Psychosomatic Research, vol. 53, no. 2, pp. 647–654, 2002. View at Publisher · View at Google Scholar · View at Scopus
  275. A. Kato, F. Ozawa, Y. Saitoh, K. Hirai, and K. Inokuchi, “vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis,” FEBS Letters, vol. 412, no. 1, pp. 183–189, 1997. View at Publisher · View at Google Scholar · View at Scopus
  276. L. M. Igaz, P. Bekinschtein, I. Izquierdo, and J. H. Medina, “One-trial aversive learning induces late changes in hippocampal CaMKIIα, homer 1a, syntaxin 1a and ERK2 protein levels,” Molecular Brain Research, vol. 132, no. 1, pp. 1–12, 2004. View at Publisher · View at Google Scholar · View at Scopus
  277. W. G. Walkup, L. Washburn, M. J. Sweredoski et al., “Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP Activity toward ras and rap GTPases,” Journal of Biological Chemistry, vol. 290, no. 8, pp. 4908–4927, 2015. View at Publisher · View at Google Scholar · View at Scopus
  278. N. H. Komiyama, A. M. Watabe, H. J. Carlisle et al., “SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor,” Journal of Neuroscience, vol. 22, no. 22, pp. 9721–9732, 2002. View at Google Scholar · View at Scopus
  279. S. A. Eichler and J. C. Meier, “E-I balance and human diseases—from molecules to networking,” Frontiers in Molecular Neuroscience, vol. 1, article 2, 2008. View at Publisher · View at Google Scholar
  280. M. Kneussel, J. H. Brandstätter, B. Laube, S. Stahl, U. Müller, and H. Betz, “Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice,” Journal of Neuroscience, vol. 19, no. 21, pp. 9289–9297, 1999. View at Google Scholar · View at Scopus
  281. B. Kirkpatrick, L. Xu, N. Cascella, Y. Ozeki, A. Sawa, and R. C. Roberts, “DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex,” The Journal of Comparative Neurology, vol. 497, no. 3, pp. 436–450, 2006. View at Publisher · View at Google Scholar
  282. L. M. Camargo, V. Collura, J.-C. Rain et al., “Disrupted in Schizophrenia 1 interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia,” Molecular Psychiatry, vol. 12, no. 1, pp. 74–86, 2007. View at Publisher · View at Google Scholar · View at Scopus
  283. X. Duan, J. H. Chang, S. Ge et al., “Disrupted-in-schizophrenia 1 regulates integration of newly generated neurons in the adult brain,” Cell, vol. 130, no. 6, pp. 1146–1158, 2007. View at Publisher · View at Google Scholar · View at Scopus
  284. A. Hayashi-Takagi, Y. Araki, M. Nakamura et al., “PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence,” Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 17, pp. 6461–6466, 2014. View at Publisher · View at Google Scholar · View at Scopus