The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome

Current Neuropharmacology

Volumn 12, Issue 1, 2014, Pages 71-98

  Uzunova, Genoveva ^a   Hollander, Eric ^a   Shepherd, Jason ^b  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

AMPA receptor; Arc; Autism spectrum disorder; Fragile X syndrome; GRIP1 2; Kainate receptor; MAP1B; Memantine; Metabotropic glutamate receptor; Neuroligin; NMDA receptor

Indexed keywords

4 AMINOBUTYRIC ACID B RECEPTOR; 4 AMINOBUTYRIC ACID RECEPTOR; ACAMPROSATE; AMANTADINE; AMPA RECEPTOR; ARIPIPRAZOLE; CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE II; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLOSERINE; DOPAMINE RECEPTOR; FLUOXETINE; FRAGILE X MENTAL RETARDATION PROTEIN; GLUTAMATE RECEPTOR 6; IONOTROPIC RECEPTOR; KAINIC ACID RECEPTOR; MAMMALIAN TARGET OF RAPAMYCIN; MEMANTINE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; METHYL CPG BINDING PROTEIN 2; METHYLPHENIDATE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUREXIN; NEUROLIGIN; PIRACETAM; RISPERIDONE; TOPIRAMATE; UNINDEXED DRUG; VALPROATE SEMISODIUM; VESICULAR GLUTAMATE TRANSPORTER;

AGGRESSION; AUTISM; BRAIN REGION; CENTRAL NERVOUS SYSTEM; CLINICAL TRIAL (TOPIC); COGNITION; FRAGILE X SYNDROME; HUMAN; IRRITABILITY; LEARNING; LONG TERM DEPRESSION; LONG TERM POTENTIATION; MEMORY; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; POLYMERASE CHAIN REACTION; RETT SYNDROME; REVIEW;

EID: 84896722575     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/1570159X113116660046     Document Type: Review

References (288)

1. American Psychiatric Association. Diagnostic and Statistic Manual of Mental Disorders, 5th Edition; American Psychiatric Publishing: Washington D. C., 2013, pp 991. ISBN: 978-1-55798-791-4, ISBN: 13: 978-0890425558.
2. Autism Developmental Disabilities Monitoring Network Surveillance, Year 2008 Principal Investigators, Center for Disease Control and Prevention. Prevalence of autism spectrum disorders-Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008, 2012, 61(3), 1-19. http://dx. doi. org/10. 3410/f. 717747905. 793252855.
3. Thurm, A.; Swedo, S. E. The importance of autism research. Dialog. Clin. Neurosci., 2012, 14(3), 219-22. PubMed ID: 23226948.
4. Hollander, E.; Kolevzon, A.; Coyle, J. T. Texbook of Autsim Spectrum Disorders; American Psychiatric Publishing: Washington, D. C., 2011, 603 pp. ISBN 978-1-58562-341-9.
5. Bagni, C.; Tassone, F.; Neri, G.; Hagerman, R. Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics. J. Clin. Invest., 2012, 22(12), 4314-22. http://dx. doi. org/10. 1172/JCI63141.
6. Gurkan, C. K.; Hagerman, R. J. Targeted treatments in autism and Fragile X syndrome. Res. Autism Spectr. Disord., 2012, 6(4), 1311-20. http://dx. doi. org/10. 1016/j. rasd. 2012. 05. 007.
7. Berry-Kravis, E., Knox A.; Hervey, C. Targeted treatments for fragile X syndrome. J. Neurodev. Disord., 2011, 3(3), 193-210.
8. Dolen, G.; Carpenter, R. L.; Ocain, T. D.; Bear M. F. Mechanismbased approaches to treating fragile X. Pharmacol. Ther., 2010, 127(1), 78-93. http://dx. doi. org/10. 1016/j. pharmthera. 2010. 02. 008.
9. Bassell, G. J.; Gross, C. Reducing glutamate signaling pays off in fragile X. Nat. Med. 2008, 14(3), 249-250. 10. 1038/nm0308-249.
10. Khwaja, O. S.; Sahin, M. Translational research: Rett syndrome and tuberous sclerosis complex. Curr. Opin. Pediatr., 2011, 23(6), 633-639. http://dx. doi. org/10. 1097/MOP. 0b013e32834c9251.
11. Neul, J. L. The relationship of Rett syndrome and MECP2 disorders to autism. Dialog. Clin. Neurosci., 2012, 14(3), 253-262. PMID: 23226951.
12. Moretti, P.; Zoghbi, H. Y. MeCP2 dysfunction in Rett syndrome and related disorders. Curr. Opin. Genet. Develop, 2006, 16(3), 276-281. http://dx. doi. org/10. 1016/j. gde. 2006. 04. 009.
13. Walsh, K. S.; Velez, J. I.; Kardel, P. G.; Imas, D. M.; Muenke, M.; Packer, R. J.; Castellanos, F. X.; Acosta, M. T. Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1. Dev. Med. Child Neurol., 2013, 55(2), 131-138. http://dx. doi. org/10. 1111/dmcn. 12038.
14. Guo, W.; Murthy, A. C.; Zhang, L.; Johnson E. B.; Schaller, E. G.; Allan, A. M.; Zhao, X. Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome. Hum. Mol. Genet., 2012, 21(3), 681-691. http://dx. doi. org/10. 1093/hmg/ddr501.
15. Berkel, S.; Marshall, C. R.; Weiss, B.; Howe, J.; Roeth, R.; Moog, U.; Endris, V.; Roberts, W.; Szatmari, P.; Pinto, D.; Bonin, M.; Riess A.; Engels, H.; Sprengel, R.; Scherer, S. W.; Rappold, G. A. Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat. Genet., 2010, 42(6), 489-491. http://dx. doi. org/10. 1038/ng. 589.
16. rd; Geigenmuller, U.; Hovhannisyan, H.; Trautman, E.; Pinard, R.; Rathmell, B.; Carpenter, R.; Margulies, D. Highthroughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism. PloS One. 2012, 7(4), e35003. Epub 2012/05/05 http://dx. doi. org/10. 1371/journal. pone. 0035003.
17. Muhle, R.; Trentacoste, S. V.; Rapin, I. The genetics of autism. Pediatrics, 2004, 113(5): e472-86. Epub 2004/05/04. http://dx. doi. org/10. 1542/peds. 113. 5. e472.
18. O'Roak, B. J.; Vives, L.; Girirajan, S.; Karakoc, E.; Krumm, N.; Coe, B. P.; Levy, R.; Ko A.; Lee, C.; Smith, J. D.; Turner, E. H.; Stanaway, I. B.; Vernot, B.; Malig, M.; Baker, C.; Reilly, B.; Akey, J. M.; Borenstein, E.; Rieder, M. J.; Nickerson, D. A.; Bernier, R.; Shendure, J.; Eichler, E. E. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 2012, 485(7393), 246-250. http://dx. doi. org/10. 1038/nature10989.
19. Betancur, C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res., 2011, 1380, 42-77. http://dx. doi. org/10. 1016/j. brainres. 2010. 11. 078.
20. Essa, M. M.; Braidy, N.; Vijayan, K. R.; Subash, S.; Guillemin, G. J. Excitotoxicity in the pathogenesis of autism. Neurotox. Res., 2013, 23(4), 393-400. http://dx. doi. org/10. 1007/s12640-012-9354-3.
21. Bhakar, A. L.; Dolen, G.; Bear, M. F. The pathophysiology of fragile X (and what it teaches us about synapses). Ann. Rev. Neurosci., 2012, 35, 417-443. http://dx. doi. org/10. 1146/annurevneuro-060909-153138.
22. Moskal, J. R.; Burgdorf, J.; Kroes, R. A.; Brudzynski, S. M.; Panksepp, J. A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism. Neurosci. Biobehav. Rev. 2011, 35(9), 1982-1988. http://dx. doi. org/10. 1016/j. neubiorev. 2011. 06. 006.
23. Shinohe, A.; Hashimoto, K.; Nakamura, K.; Tsujii, M.; Iwata, Y.; Tsuchiya, K. J.; Sekine, Y.; Suda, S.; Suzuki, K.; Sugihara, G.; Matszukai, H.; Minabi, Y.; Sugiyama, T.; Kawai, M.; Iyo, M.; Takei, N., Mori, N. Increased serum levels of glutamate in adult patients with autism. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2006, 30(8), 1472-1477. http://dx. doi. org/10. 1016/j. pnpbp. 2006. 06. 013.
24. Chao, H. T.; Chen, H.; Samaco R. C.; Xue, M.; Chahrour, M.; Yoo, J.; Neul, J. L.; Gong, S.; Lu, H. C.; Heintz, N.; Ekker, M.; Rubenstein J. L.; Neobels, J. L.; Rosenmund, C.; Zoghbi, H. Y. Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature, 2010, 468(7321), 263-269. 10. 1038/nature09582.
25. Harrington, R. A.; Lee, L. C.; Crum, R. M.; Zimmerman A. W.; Hertz-Picciotto, I. Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy. Autism Res., 2013, 6(3), 149-168. DOI: http://dx. doi. org/10. 1002/aur. 1288.
26. Karam, R. A.; Rezk, N. A.; Abdelrahman, H. M.; Hassan, T. H.; Mohammad, D.; Hashim, H. M.; Fattah, N. R. Catechol-Omethyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder. Res. Develop. Disabil., 2013, 34(7), 2092-2097.
27. Karam R. A.; Rezk N. A.; Abdelrahman H. M.; Hassan T. H.; Mohammad D.; Hashim H. M.; Fattah N. R. Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder. Research in Developmental Disabilities, 2013, 34(7), 2092-7. CrossRef DOI: http://dx. doi. org/10. 1016/j. ridd. 2013. 04. 002.
28. Bodner, K. E.; Beversdorf, D. Q.; Saklayen, S. S.; Christ, S. E. Noradrenergic moderation of working memory impairments in adults with autism spectrum disorder. J. Int. Neuropsychol. Soc., 2012, 18(3), 556-564. http://dx. doi. org/10. 1017/S1355617712000070.
29. Dichter, G. S.; Damiano, C. A.; Allen, J. A. Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. J. Neurodev. Dis., 2012, 4(1), 19. Epub 2012/09/11. http://dx. doi. org/10. 1186/1866-1955-4-19.
30. Arnold, L. E.; Aman, M. G.; Hollway J.; Hurt, E.; Bates, B.; Li, X.; Farmer, C.; Anand, R.; Thompson S.; Ramadan Y.; Williams C. Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders. J. Child Adolesc. Psychopharmacol., 2012, 22(3), 198-205. http://dx. doi. org/10. 1089/cap. 2011. 0056.
31. Palma, E.; Conti, L.; Roseti, C.; Limatola, C. Novel approaches to study the involvement of alpha7-nAChR in human diseases. Curr. Drug Targets, 2012, 13(5), 579-586. PMID: 22300023.
32. Jung K. M.; Sepers M.; Henstridge C. M.; Lassalle O.; Neuhofer D.; Martin H.; Ginger M.; Frick A.; DiPatricio N. V.; Mackie K.; Katona I.; Piomelli D.; Manzoni O. J. Uncoupling of the endocannabinoid signalling complex in a mouse model of fragile X syndrome. Nat. Communic., 2012, 3, 1080. Epub 2012/09/27. http://dx. doi. org/10. 1038/ncomms2045.
33. Busquets-Garcia, A.; Gomis-Gonzalez, M.; Guegan, T.; Agustin-Pavon, C.; Pastor, A.; Mato, S.; Perez-Samartin A.; Matute, C.; de la Torre, R.; Dierrsen, M.; Maldonaldo, R.; Ozaita, A. Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat. Med., 2013, 19(5), 603-607. http://dx. doi. org/10. 1038/nm. 3127.
34. Zink, C. F.; Meyer-Lindenberg, A. Human neuroimaging of oxytocin and vasopressin in social cognition. Horm. Behav., 2012, 61(3), 400-409. http://dx. doi. org/10. 1016/j. yhbeh. 2012. 01. 016.
35. Green, J. J.; Hollander, E. Autism and oxytocin: new developments in translational approaches to therapeutics. Neurotherapeutics, 2010, 7(3), 250-257. http://dx. doi. org/10. 1016/j. nurt. 2010. 05. 006.
36. Bartz, J. A.; Hollander, E. The neuroscience of affiliation: forging links between basic and clinical research on neuropeptides and social behavior. Horm. Behav., 2006, 50(4), 518-528. http://dx. doi. org/10. 1016/j. yhbeh. 2006. 06. 018.
37. Spooren, W.; Lindemann, L.; Ghosh, A.; Santarelli, L. Synapse dysfunction in autism: a molecular medicine approach to drug discovery in neurodevelopmental disorders. Trends Pharmacol. Sci., 2012, 33(12), 669-684. http://dx. doi. org/10. 1016/j. tips. 2012. 09. 004.
38. Soorya, L.; Kiarashi, J.; Hollander, E. Psychopharmacologic interventions for repetitive behaviors in autism spectrum disorders. Child Adoles. Psychiatr. Clin. N. Am., 2008, 17(4), 753-771. 10. 1016/j. chc. 2008. 06. 003.
39. Hollander, E.; Phillips, A. T.; Yeh, C. C. Targeted treatments for symptom domains in child and adolescent autism. Lancet, 2003, 362(9385), 732-734. 10. 1016/S0140-6736(03)14236-5.
40. Doyle, C. A.; McDougle, C. J. Pharmacotherapy to control behavioral symptoms in children with autism. Expert Opin. Pharmacother., 2012, 13(11), 1615-1629. http://dx. doi. org/10. 1016/S0140-6736(03) 14236-5.
41. Tranfaglia, M. R. Fragile X syndrome: a psychiatric perspective. Results Probl. Cell Differ., 2012, 54, 281-295. http://dx. doi. org/10. 1007/978-3-642-21649-7-16.
42. Hagerman, R. J.; Berry-Kravis, E.; Kaufmann, W. E.; Ono, M. Y.; Tartaglia, N.; Lachiewicz A.; Kronk, R.; Delahunty, C.; Hessl, D.; Visootsak, J.; Picker, J.; Gane, L.; Tranfaglia, M. Advances in the treatment of fragile X syndrome. Pediatrics, 2009, 123(1), 378-390.
43. Berry-Kravis, E.; Hessl, D.; Coffey, S.; Hervey, C.; Schneider, A.; Yuhas, J.; Hutchison, J.; Snape, M.; Tranfaglia, M.; Ngyuen, D. V.; Hagerman, R. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J. Med. Genet., 2009, 46(4), 266-271. http://dx. doi. org/10. 1136/jmg. 2008. 063701.
44. Jacquemont, S.; Curie, A.; des Portes, V.; Torrioli, M. G.; Berry-Kravis, E.; Hagerman, R. J., Ramos, F. J.; Cornish, K.; He, Y.; Paulding, C.; Neri, G.; Chen F.; Hadjikhani, N.; Martinet, D.; Meyer J.; Beckmann, J. S.; Delange, K.; Brun, A.; Bussy G.; Gasparini F.; Hilse, T.; Floesser, A.; Branson, J.; Bilbe, G.; Johns, D.; Gomez-Mancilla, B. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci. Transl. Med., 2011, 3(64), 64ra1. Epub 2011/01/07.
45. Gandal, M. J.; Edgar, J. C.; Ehrlichman, R. S.; Mehta, M.; Roberts, T. P.; Siegel, S. J. Validating gamma oscillations and delayed auditory responses as translational biomarkers of autism. Biol. Psychiatry, 2010, 68(12), 1100-1106. http://dx. doi. org/10. 1016/j. biopsych. 2010. 09. 031.
46. Mehta, M. V.; Gandal, M. J.; Siegel, S. J. mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism. PloS One., 2011, 6(10), e26077. Epub 2011/10/22. http://dx. doi. org/10. 1371/journal. pone. 0026077.
47. Silverman, J. L.; Smith, D. G.; Rizzo, S. J.; Karras, M. N.; Turner, S. M.; Tolu, S. S.; Bryce, D. K.; Smith, D. L.; Fonseca, K.; Ring, R. H.; Crawley J. N. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci. Transl. Med., 2012, 4(131), 131ra51. Epub 2012/04/28. http://dx. doi. org/10. 1126/scitranslmed. 3003501.
48. Berry-Kravis, E.; Hessl, D.; Rathmell, B.; Zarevics, P. Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci. Transl. Med., 2012, 4(152), 152ra127. doi: 10. 1155/2012/843016.
49. Burket, J. A.; Herndon, A. L.; Winebarger, E. E.; Jacome, L. F.; Deutsch, S. I. Complex effects of mGluR5 antagonism on sociability and stereotypic behaviors in mice: possible implications for the pharmacotherapy of autism spectrum disorders. Brain Res. Bull., 2011, 86(3-4), 152-158. http://dx. doi. org/10. 1016/j. brainresbull. 2011. 08. 001.
50. Mayer, M. L. Emerging models of glutamate receptor ion channel structure and function. Structure, 2011, 19(10), 1370-1380. http://dx. doi. org/10. 1016/j. str. 2011. 08. 009.
51. Mayer, M. L. Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation. Curr. Opin. Neurobiol., 2011, 21(2), 283-290. http://dx. doi. org/10. 1016/j. conb. 2011. 02. 001.
52. Traynelis, S. F; Wollmuth, L. P.; McBain, C. J.; Menniti, F. S.; Vance, K. M.; Ogden, K. K., Hansen, K. B.; Yuan, H.; Myers, S. J.; Dingledine, R. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol. Rev., 2010, 62(3), 405-496. http://dx. doi. org/10. 1124/pr. 109. 002451.
53. Collingridge, G. L.; Olsen, R.; Peters, J.; Spedding, M. A nomenclature for ligand-gated ion channels. Neuropharmacology, 2009, 56(1), 2-5. http://dx. doi. org/10. 1016/j. neuropharm. 2008. 06. 063.
54. Contractor, A.; Swanson, G.; Heinemann, S. F. Kainate receptors are involved in short-and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron, 2001, 29(1), 209-216. http://dx. doi. org/10. 1016/S0896-6273(01)00191-X.
55. Contractor, A.; Mulle, C.; Swanson, G. T. Kainate receptors coming of age: milestones of two decades of research. Trends Neurosci., 2011, 34(3), 154-163. http://dx. doi. org/10. 1016/j. tins. 2010. 12. 002.
56. Nicoletti, F.; Bockaert, J.; Collingridge, G. L.; Conn, P. J.; Ferraguti, F.; Schoepp, D. D., Wroblewski, J. T.; Pin, J. P. Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology, 2011, 60(7-8), 1017-1041. http://dx. doi. org/10. 1016/j. neuropharm. 2010. 10. 022.
57. Lau, C. G.; Zukin, R. S. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat. Rev. Neurosci., 2007, 8(6), 413-426. http://dx. doi. org/10. 1038/nrn2153.
58. Shepherd, J. D.; Huganir, R. L. The cell biology of synaptic plasticity: AMPA receptor trafficking. Ann. Rev. Cell Develop. Biol., 2007, 23, 613-643. http://dx. doi. org/10. 1146/annurev. cellbio. 23. 090506. 123516.
59. Anggono, V.; Huganir, R. L. Regulation of AMPA receptor trafficking and synaptic plasticity. Curr. Opin. Neurobiol., 2012, 22(3), 461-469. http://dx. doi. org/10. 1016/j. conb. 2011. 12. 006.
60. Wang, G.; Gilbert, J.; Man, H. Y. AMPA receptor trafficking in homeostatic synaptic plasticity: functional molecules and signaling cascades. Neural Plast., 2012, 2012, 825364. Epub 2012/06/02. 10. 1155/2012/825364.
61. Lu, W.; Roche, K. W.; Posttranslational regulation of AMPA receptor trafficking and function. Curr. Opin. Neurobiol., 2012, 22(3), 470-479. http://dx. doi. org/10. 1016/j. conb. 2011. 09. 008.
62. Sanz-Clemente, A.; Nicoll, R. A.; Roche, K. W. Diversity in NMDA receptor composition: many regulators, many consequences. Neuroscientist, 2013, 19(1), 62-75. http://dx. doi. org/10. 1177/1073858411435129.
63. Fourie C.; Li, D.; Montgomery, J. M. The anchoring protein SAP97 influences the trafficking and localisation of multiple membrane channels. Bioch. Biophys. Acta, 2013. Epub 2013/03/29. http://dx. doi. org/10. 1016/j. bbamem. 2013. 03. 015.
64. Shen, L.; Liang F.; Walensky, L. D.; Huganir, R. L. Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1Nlinked actin cytoskeletal association. J. Neurosci., 2000, 20(21), 7932-7940. PMID: 11050113.
65. Xia, J.; Zhang, X.; Staudinger, J.; Huganir, R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron, 1999, 22(1), 179-187. http://dx. doi. org/10. 1016/S0896-6273(00)80689-3.
66. Dong, H.; O'Brien, R. J.; Fung, E. T.; Lanahan A. A.; Worley P. F.; Huganir, R. L. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature, 1997, 386(6622), 279-284. http://dx. doi. org/10. 1038/386279a0.
67. Nishimune, A.; Isaac, J. T.; Molnar, E.; Noel, J.; Nash, S. R.; Tagaya, M.; Collingridge, G. L.; Nakanishi, S.; HeNLGNey J. M. NSF binding to GluR2 regulates synaptic transmission. Neuron, 1998, 21(1), 87-97. http://dx. doi. org/10. 1016/S0896-6273(00)80517-6.
68. Li, D.; Specht, C. G.; Waites, C. L.; Butler-Munro, C.; Leal-Ortiz, S.; Foote, J. W.; Genoux, D.; Garner, C. C.; Montgomery, J. M. SAP97 directs NMDA receptor spine targeting and synaptic plasticity. J. Physiol., 2011, 589 (Pt 18), 4491-510. http://dx. doi. org/10. 1113/jphysiol. 2011. 215566.
69. Howard, M. A.; Elias, G. M.; Elias, L. A.; Swat, W.; Nicoll, R. A. The role of SAP97 in synaptic glutamate receptor dynamics. Proc. Natl. Acad. Sci. U. S. A., 2010, 107(8), 3805-3810. http://dx. doi. org/10. 1073/pnas. 0914422107.
70. Xu, W. PSD-95-like membrane associated guanylate kinases (PSDMAGUKs) and synaptic plasticity. Curr. Opin. Neurobiol., 2011, 21(2), 306-312. http://dx. doi. org/10. 1016/j. conb. 2011. 03. 001.
71. Bhattacharyya, S.; Biou, V.; Xu, W.; Schluter, O.; Malenka, R. C. A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nat. Neurosci. 2009, 12(2), 172-181. http://dx. doi. org/10. 1038/nn. 2249.
72. Bats, C.; Groc, L.; Choquet, D. The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron, 2007, 53(5), 719-734. http://dx. doi. org/10. 1016/j. neuron. 2007. 01. 030.
73. Beique, J. C.; Lin, D. T.; Kang, M. G.; Aizawa, H.; Takamiya K.; Huganir, R. L. Synapse-specific regulation of AMPA receptor function by PSD-95. Proc. Natl. Acad. Sci. USA, 2006, 103(51), 19535-19540. http://dx. doi. org/10. 1073/pnas. 0608492103.
74. Elias, G. M.; Elias, L. A.; Apostolides, P. F.; Kriegstein, A. R.; Nicoll, R. A. Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development. Proc. Natl. Acad. Sci. U. S. A., 2008, 105(52), 20953-20958. http://dx. doi. org/10. 1073/pnas. 0811025106.
75. Lin, Y.; Jover-Mengual, T.; Wong, J.; Bennett, M. V.; Zukin, R. S. PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating. Proc. Natl. Acad. Sci. U. S. A., 2006, 103(52), 19902-19907. http://dx. doi. org/10. 1073/pnas. 0609924104.
76. Straub, C.; Tomita, S. The regulation of glutamate receptor trafficking and function by TARPs and other transmembrane auxiliary subunits. Curr. Opin. Neurobiol., 2012, 22(3), 488-495. http://dx. doi. org/10. 1016/j. conb. 2011. 09. 005.
77. Groc, L.; Choquet, D. AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse. Cell Tissue Res., 2006, 326(2), 423-438. http://dx. doi. org/10. 1007/s00441-006-0254-9.
78. Perez-Otano, I.; Ehlers, M. D. Homeostatic plasticity and NMDA receptor trafficking. Trends Neurosci., 2005, 28(5), 229-238. http://dx. doi. org/10. 1016/j. tins. 2005. 03. 004.
79. Carroll, R. C.; Zukin, R. S. NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity. Trends Neurosci., 2002, 25(11), 571-577. http://dx. doi. org/10. 1016/S0166-2236(02)02272-5.
80. Malenka, R. C. Synaptic plasticity and AMPA receptor trafficking. Ann. N. Y. Acad. Sci., 2003, 1003, 1-11. http://dx. doi. org/10. 1196/annals. 1300. 001.
81. Carroll, R. C.; Beattie, E. C.; von Zastrow, M.; Malenka, R. C. Role of AMPA receptor endocytosis in synaptic plasticity. Nat. Rev. Neurosci., 2001, 2(5), 315-324. PMID: 11331915.
82. Choquet, D. Fast AMPAR trafficking for a high-frequency synaptic transmission. Eur. J. Neurosci., 2010, 32(2), 250-260. http://dx. doi. org/10. 1111/j. 1460-9568. 2010. 07350. x.
83. Malenka, R. C.; Bear, M. F. LTP and LTD: an embarrassment of riches. Neuron, 2004, 44(1), 5-21. http://dx. doi. org/10. 1016/j. neuron. 2004. 09. 012.
84. Huber, K. M.; Gallagher, S. M.; Warren, S. T.; Bear, M. F. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA, 2002, 99(11), 7746-7750. http://dx. doi. org/10. 1073/pnas. 122205699.
85. Krugers, H. J.; Hoogenraad, C. C.; Groc, L. Stress hormones and AMPA receptor trafficking in synaptic plasticity and memory. Nat. Rev. Neurosci., 2010, 11(10), 675-681. http://dx. doi. org/10. 1038/nrn2913.
86. Stellwagen, D.; Malenka R. C. Synaptic scaling mediated by glial TNF-alpha. Nature, 2006, 440(7087), 1054-1059. http://dx. doi. org/10. 1038/nature04671.
87. Soden M. E.; Chen, L. Fragile X protein FMRP is required for homeostatic plasticity and regulation of synaptic strength by retinoic acid. J. Neurosci., 2010, 30(50), 16910-16921.
88. Anggono, V.; Clem, R. L.; Huganir R. L. PICK1 loss of function occludes homeostatic synaptic scaling. J. Neurosci., 2011, 31(6), 2188-2196. http://dx. doi. org/10. 1523/JNEUROSCI. 3660-10. 2010.
89. Shepherd, J. D.; Rumbaugh, G.; Wu J.; Chowdhury, S.; Plath, N.; Kuhl, D.; Huganir, R. L.; Worley P. F. Arc/Arg3. 1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron, 2006, 52(3), 475-484. http://dx. doi. org/10. 1523/JNEUROSCI. 5633-10. 2011.
90. Hou, Q.; Zhang, D.; Jarzylo, L.; Huganir, R. L.; Man, H. Y. Homeostatic regulation of AMPA receptor expression at single hippocampal synapses. Proc. Natl. Acad. Sci. U. S. A., 2008, 105(2), 775-780. http://dx. doi. org/10. 1073/pnas. 0706447105.
91. Isaac, J. T.; Nicoll, R. A.; Malenka, R. C. Silent glutamatergic synapses in the mammalian brain. Can. J. Physiol. Pharmacol., 1999, 77(9), 735-737. PMID: 10566951.
92. Isaac, J. T.; Crair, M. C.; Nicoll, R. A.; Malenka, R. C. Silent synapses during development of thalamocortical inputs. Neuron, 1997, 18(2), 269-280. 10. 1016/S0896-6273(00)80267-6.
93. Hall, B. J.; Ripley, B.; Ghosh, A. NR2B signaling regulates the development of synaptic AMPA receptor current. J. Neurosci., 2007, 27(49), 13446-56. http://dx. doi. org/10. 1523/JNEUROSCI. 3793-07. 2007.
94. Liao, D., Zhang, X., O'Brien, R., Ehlers, M. D., Huganir, R. L. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nat. Neurosci., 1999, 2(1), 37-43. PMID: 10195178.
95. Adesnik, H.; Li, G.; During, M. J; Pleasure, S. J.; Nicoll, R. A. NMDA receptors inhibit synapse unsilencing during brain development. Proc. Natl. Acad. Sci. USA, 2008, 105(14), 5597-5602. http://dx. doi. org/10. 1073/pnas. 0800946105.
96. Alvarez, V. A.; Ridenour, D. A.; Sabatini, B. L. Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability. J. Neurosci, 2007, 27(28), 7365-7376. http://dx. doi. org/10. 1523/JNEUROSCI. 0956-07. 2007.
97. Hall, B. J.; Ghosh, A. Regulation of AMPA receptor recruitment at developing synapses. Trends Neurosci., 2008, 31(2), 82-89. http://dx. doi. org/10. 1016/j. tins. 2007. 11. 010.
98. Luscher, C.; Malenka, R. C. NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb. Perspect. Biol., 2012, 4(6). Epub 2012/04/19. http://dx. doi. org/10. 1101/cshperspect. a005710.
99. Gainey, M. A.; Hurvitz-Wolff, J. R.; Lambo, M. E.; Turrigiano, G. G. Synaptic scaling requires the GluR2 subunit of the AMPA receptor. J. Neurosci., 2009, 29(20), 6479-6489. http://dx. doi. org/10. 1523/JNEUROSCI. 3753-08. 2009.
100. Malinow, R. AMPA receptor trafficking and long-term potentiation. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 2003, 358(1432), 707-714. http://dx. doi. org/10. 1098/rstb. 2002. 1233.
101. Citri, A.; Bhattacharyya, S.; Ma, C.; Morishita, W.; Fang, S.; Rizo, J.; Malenka, R. C. Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression. J. Neurosci., 2010, 30(49), 16437-16452. http://dx. doi. org/10. 1523/JNEUROSCI. 4478-10. 2010.
102. Snyder, E. M.; Philpot, B. D.; Huber, K. M.; Dong, X.; Fallon, J. R.; Bear, M. F. Internalization of ionotropic glutamate receptors in response to mGluR activation. Nat. Neurosci, 2001, 4(11), 1079-1085. PMID: 11687813.
103. Xiao, M. Y.; Zhou, Q.; Nicoll, R. A. Metabotropic glutamate receptor activation causes a rapid redistribution of AMPA receptors. Neuropharmacology, 2001, 41(6), 664-671. http://dx. doi. org/10. 1016/S0028-3908(01)00134-4.
104. Davidkova, G.; Carroll, R. C. Characterization of the role of microtubule-associated protein 1B in metabotropic glutamate receptor-mediated endocytosis of AMPA receptors in hippocampus. J. Neurosci., 2007, 27(48), 13273-13278. http://dx. doi. org/10. 1523/JNEUROSCI. 3334-07. 2007.
105. Lee, H. K.; Takamiya, K.; He, K.; Song, L.; Huganir, R. L. Specific roles of AMPA receptor subunit GluR1 (GluA1) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. J. Neurophysiol., 2010, 103(1), 479-489. http://dx. doi. org/10. 1152/jn. 00835. 2009.
106. Makino, Y.; Johnson, R. C.; Yu, Y.; Takamiya, K.; Huganir, R. L. Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(20), 8450-8455. http://dx. doi. org/10. 1152/jn. 00835. 2009.
107. Lee, H. K.; Kameyama, K.; Huganir, R. L.; Bear, M. F. NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus. Neuron, 1998, 21(5), 1151-1162. http://dx. doi. org/10. 1016/S0896-6273(00) 80632-7.
108. Lee, H. K.; Takamiya, K.; Han, J. S.; Man, H.; Kim, C. H.; Rumbaugh G.; Yu, S.; Ding, L.; He, C.; Petralia, R. S.; Wnthold, R. J.; Gallagher, M.; Huganir, R. L. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell, 2003, 112(5), 631-643. http://dx. doi. org/10. 1016/S0092-8674(03)00122-3.
109. Boehm, J.; Kang, M. G.; Johnson, R. C.; Esteban, J.; Huganir, R. L.; Malinow, R. Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1. Neuron, 2006, 51(2), 213-225. http://dx. doi. org/10. 1016/j. neuron. 2006. 06. 013.
110. Bliss, T. V.; Collingridge, G. L. Expression of NMDA receptordependent LTP in the hippocampus: bridging the divide. Mol. Brain, 2013, 6, 5. Epub 2013/01/24. http://dx. doi. org/10. 1186/1756-6606-6-5.
111. Nosyreva, E. D.; Huber, K. M. Developmental switch in synaptic mechanisms of hippocampal metabotropic glutamate receptordependent long-term depression. J. Neurosci., 2005, 25(11), 2992-3001. http://dx. doi. org/10. 1523/JNEUROSCI. 3652-04. 2005.
112. Dickinson, B. A.; Jo, J.; Seok, H.; Son, G. H.; Whitcomb D. J.; Davies, C. H.; Sheng, M.; Collingridge, G. L.; Cho K. A novel mechanism of hippocampal LTD involving muscarinic receptortriggered interactions between AMPARs, GRIP and liprin-alpha. Mol. Brain, 2009, 2, 18. Epub 2009/06/19. http://dx. doi. org/10. 1186/1756-6606-2-18.
113. Volk, L. J.; Pfeiffer, B. E.; Gibson, J. R.; Huber, K. M. Multiple Gqcoupled receptors converge on a common protein synthesisdependent long-term depression that is affected in fragile X syndrome mental retardation. J. Neurosci., 2007, 27(43), 11624-11634. http://dx. doi. org/10. 1523/JNEUROSCI. 2266-07. 2007.
114. Bramham, C. R.; Worley, P. F.; Moore, M. J.; Guzowski, J. F. The immediate early gene arc/arg3. 1: regulation, mechanisms, and function. J. Neurosci., 2008, 28(46), 11760-11767. http://dx. doi. org/10. 1523/JNEUROSCI. 3864-08. 2008.
115. Carlsson, M. L. Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interactions for pharmacotherapy. J. Neural Transm., 1998, 105(4-5), 525-535. 10. 1186/1471-2350-5-10.
116. Bejjani, A.; O'Neill, J.; Kim, J. A.; Frew, A. J.; Yee, V. W.; Ly R.; Kitchen, C.; Salamon, N.; McCracken, J. T.; Toga, A. W.; Alger, J. R.; Levitt, J. G. Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI. PloS One, 2012, 7(7), e38786. Epub 2012/08/01. http://dx. doi. org/10. 1371/journal. pone. 0038786.
117. Akhondzadeh, S.; Tajdar, H.; Mohammadi, M. R.; Mohammadi, M.; Nouroozinejad, G. H.; Shabstari O. L.; Ghelichnia H. A. A double-blind placebo controlled trial of piracetam added to risperidone in patients with autistic disorder. Child Psychiatry Hum. Dev., 2008, 39(3), 237-245. http://dx. doi. org/10. 1007/s10578-007-0084-3.
118. Chen, H. S.; Pellegrini, J. W.; Aggarwal, S. K.; Lei, S. Z.; Warach, S.; Jensen, F. E.; Lipton, S. A. Open-channel block of N-methyl-Daspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. J. Neurosci., 1992, 12(11), 4427-4436. PMID: 1432103.
119. Ghaleiha, A.; Asadabadi, M.; Mohammadi, M. R.; Shahei, M.; Tabrizi, M.; Hajiaghaee, R.; Akhonzhadeh, S. Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial. Int. J. Neuropsychopharmacol., 2013, 16(4), 783-789. http://dx. doi. org/10. 1017/S1461145712000880.
120. Chow, M.; Parmparo, T.; Winn, M.; Barnes, C.; Li H.; Weiss, L.; Fan J.; Murray, S.; April, C.; Belinson, H.; Fu, X. Wynshaw-Boris, A.; Schork, N.; Courchesne, E. Age-dependent brain gene expression and copy number anomalies in autism suggest distinc pathological processes at young versus mature ages. PloS Genet., 2012, 8(3), e1002592. 10. 1371/journal. pgen. 1002592.
121. O'Roak, B. J.; Vives, L.; Girirajan, S.; Karakoc, E.; Krumm, N.; Coe, BP.; Levy, R.; Ko, A.; Lee C.; Smith, J. D.; Turner, E. H.; Stanaway I. B.; Vernot, B.; Malig M.; Baker, C.; Reilly, B.; Akey, J. M.; Borenstein, E.; Rieder, M. J.; Nickerson, D. A.; Bernier, R.; Shendure, J.; Eichler, E. E. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 2012, 485(7397), 246-250. http://dx. doi. org/10. 1038/nature10989.
122. Yoo, H. J.; Cho, I. H.; Park, M.; Yang, S. Y.; Kim, S. A. Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders. Neurosci. Lett., 2012, 512(2), 89-93. http://dx. doi. org/10. 1016/j. neulet. 2012. 01. 061.
123. Barnby, G.; Abbott, A.; Sykes, N.; Morris, A.; Weeks, D. E.; Mott, R.; Lamb, J.; Bailey, A. J.; Monaco, A. P. International Molecular Genetics Study of Autism Consortium. Candidate-gene screening and association analysis at the autism-susceptibility locus on chromosome 16p: evidence of association at GRIN2A and ABAT. Am. J. Hum. Genet., 2005, 76(6), 950-966. http://dx. doi. org/10. 1086/430454.
124. Tarabeux, J.; Kebir, O.; Gauthier, J.; Hamdan, F. F.; Xiong, L.; Piton, A.; Spiegelman, D.; Henrion, É.; Millet, B.; Fathalli, F.; Joober, R.; Rapoport, J. L.; DeLisi L. E.; Fombonne, É.; Mottron, L.; Forget-Dubois, N.; Boivin, M.; Michaud, J. L.; Drapeau, P.; Lafrenière, R, G.; Rouleau, G. A.; Krebs, M. O. Rare mutations in Nmethyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl. Psychiatry, 2011, 1, e55. Epub 2011/01/01. http://dx. doi. org/10. 1038/tp. 2011. 52.
125. Endele, S.; Rosenberger G.; Geider K.; Popp, B.; Tamer, C.; Stefanova, I.; Milh M.; Kortüm F.; Fritsch A.; Pientka, F. K.; Hellenbroich, Y.; Kalscheuer V. M.; Kohlhase, J.; Moog, U.; Rappold, G.; Rauch, A.; Ropers, H. H.; von Spiczak, S.; Tönnies, H.; Villeneuve, N.; Villard L.; Zabel, B.; Zenker, M.; Laube B.; Reis, A.; Wieczorek, D.; Van Maldergem, L.; Kutsche, K. Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nat. Genet., 2010, 42(11), 1021-1026. http://dx. doi. org/10. 1038/ng. 677.
126. Ramanathan, S.; Woodroffe A.; Flodman, P. L.; Mays, L. Z.; Hanouni, M.; Modahl, C. B.; Steinberg-Epstein, R.; Bocian, M. E.; Spence, M. A.; Smith, M. 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 Med. Genet., 2004, 5, 10. Epub 2004/04/20. PMID: 15090072.
127. Jamain, S.; Betancur, C.; Quach, H.; Philippe, A.; Fellous, M.; Giros, B.; Gillberg, C.; Leboyer, M.; Bourgeron T. Linkage and association of the glutamate receptor 6 gene with autism. Mol. Psychiatry, 2002, 7(3), 302-310. http://dx. doi. org/10. 1038/sj. mp. 4000979.
128. Shuang, M.; Liu, J.; Jia, M. X.; Yang J. Z.; Wu, S. P.; Gong, X. H.; Ling, Y. S.; Ruan, Y.; Yang, X. L.; Zhang D. Family-based association study between autism and glutamate receptor 6 gene in Chinese Han trios. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2004, 131B(1), 48-50. http://dx. doi. org/10. 1002/ajmg. b. 30025.
129. Motazacker, M. M.; Rost, B. R.; Hucho, T.; Garshasbi, M.; Kahrizi, K.; Ullmann, R.; Abedini, S. S.; Nieh, S. E.; Amini, S. H.; Goswami, C.; Tzschach, A.; Jensen, L. R.; Schmitz, D.; Ropers, H. H.; Najmabadi, H.; Kuss, A. W. A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. Am. J. Hum. Genet., 2007, 81(4), 792-798. http://dx. doi. org/10. 1086/521275.
130. Ramoz, N.; Reichert, J. G.; Smith, C. J.; Silverman J. M.; Bespalova, I. N.; Davis, K. L.; Buxbaum, J. D. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am. J. Psychiat., 2004, 161(4), 662-669. http://dx. doi. org/10. 1176/appi. ajp. 161. 4. 662.
131. Autism Genome Project Consortium; Szatmari, P.; Paterson, A. D.; Zwaigenbaum, L.; Roberts, W.; Brian, J. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat. Genet., 2007, 39(3), 319-328. PMID: 17322880.
132. Mejias, R.; Adamczyk, A.; Anggono, V.; Niranjan, T.; Thomas, GM.; Sharma, K.; Skinner, C.; Schwartz, C. E.; Stevenson, R. E.; Fallin, M. D.; Kaufman, W.; Pletnikov, M.; Valle, D.; Huganir, R. L.; Wang, T. Gain-of-function glutamate receptor interacting protein 1 variants alter GluA2 recycling and surface distribution in patients with autism. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(12), 4920-4925. http://dx. doi. org/10. 1073/pnas. 1102233108.
133. Gauthier, J.; Spiegelman, D.; Piton, A.; Lafreniere, R. G.; Laurent, S.; St-Onge J.; et al. Novel de novo SHANK3 mutation in autistic patients. Am. J. Med. Genet. B. Neuropsychiatr. Genet., 2009, 150B(3), 421-424. 10. 1002/ajmg. b. 30822.
134. Moessner, R.; Marshall C. R.; Sutcliffe, J. S.; Skaug, J.; Pinto, D.; Vincent, J.; Zwaigenbaum, L.; Fernandez, B.; Roberts, W.; Szatmari, P.; Scherer, S. W. Contribution of SHANK3 mutations to autism spectrum disorder. Am. J. Hum. Genet., 2007, 81(6), 1289-1297. http://dx. doi. org/10. 1086/522590.
135. Chilian, B.; Abdollahpour, H.; Bierhals, T.; Haltrich, I.; Fekete, G.; Nagel, I.; Rosenberger, G.; Kutsche, K. Dysfunction of SHANK2 and CHRNA7 in a patient with intellectual disability and language impairment supports genetic epistasis of the two loci. Clin. Genet, 2013. Epub 2013/01/29. http://dx. doi. org/10. 1111/cge. 12105.
136. Bucan, M.; Abrahams, B. S.; Wang, K.; Glessner, J. T.; Herman, E. I.; Sonnenblick, L. I.; Alvarez, R, A. I.; Imielinski, M.; Hadley, D.; Bradfield, J. P.; Kim, C.; Gidaya, N. B.; Lindquist, I.; Hutman, T.; Sigman, M.; Kustanovich, V.; Lajonchere C. M.; Singleton A.; Kim, J.; Wassink, T. H.; McMahon, W. M.; Owley, T.; Sweeney, J. A.; Coon H.; Nurnberger, J. I.; Li, M.; Cantor, R. M.; Minshew, N. J.; Sutcliffe, J. S.; Cook, E. H.; Dawson, G.; Buxbaum, J. D.; Grant, S. F.; Schellenberg, G. D.; Geschwind, D. H.; Hakonarson, H. Genome-wide analyses of exonic copy number variants in a familybased study point to novel autism susceptibility genes. PLoS Genet., 2009, 5(6), e1000536. Epub 2009/06/27. http://dx. doi. org/10. 1371/journal. pgen. 1000536.
137. Nurmi, E. L.; Bradford, Y.; Chen, Y.; Hall, J.; Arnone, B.; Gardiner, M. B.; Hutcheson, H. B.; Gilbert, J. R.; Pericak-Vance, M. A.; Copeland-Yates, S. A.; Michaelis, R. C.; Wassink, T. H.; Santangelo S. L.; Sheffield, V. C.; Piven, J.; Folstein S. E.; Haines J. L.; Sutcliffe, J. S. Linkage disequilibrium at the Angelman syndrome gene UBE3A in autism families. Genomics, 2001, 77(1-2), 105-113.
138. Jamain, S.; Quach, H.; Betancur, C.; Rastam, M.; Colineaux, C.; Gillberg, I. C.; Soderstrom, H.; Giros, B.; Leboyer, M.; Gillberg, C.; Bourgeron, T. Paris International Autism Sibpair Study. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet., 2003, 34(1), 27-29. http://dx. doi. org/10. 1038/ng1136.
139. Laumonnier, F.; Bonnet-Brilhault, F.; Gomot, M.; Blanc, R.; David, A.; Moizard, M. P.; Raynaud M.; Ronche, N.; Calvas, P.; Laudier, B.; Chelly, J.; Fryns, J. P; Ropers, H. H.; Hamel, B. C.; Andres, C.; Barthelemy, C.; Moraine, C.; Briault, S. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet., 2004, 74(3), 552-557. http://dx. doi. org/10. 1086/382137.
140. Yan, J.; Oliveira, G.; Coutinho, A.; Yang, C.; Feng, J.; Katz, C.; Sram, J.; Bockholt, A.; Jones, I. R.; Craddock, N.; Cook, E. H.; Vicente, A.; Sommer S. S. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol. Psychiatry, 2005, 10(4), 329-332. http://dx. doi. org/10. 1038/sj. mp. 4001629.
141. Talebizadeh, Z.; Lam, D. Y.; Theodoro, M. F.; Bittel, D. C.; Lushington, G. H.; Butler, M. G. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet., 2006, 43(5), e21. Epub 2006/05/02. http://dx. doi. org/10. 1136/jmg. 2005. 036897.
142. Lawson-Yuen, A.; Saldivar J. S.; Sommer S.; Picker J. Familial deletion within NLGNGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet., 2008, 16(5), 614-618. http://dx. doi. org/10. 1038/sj. ejhg. 5202006.
143. Sudhof, T. C. Neuroligins and neurexins link synaptic function to cognitive disease. Nature, 2008, 455(7215), 903-11. http://dx. doi. org/10. 1038/nature07456.
144. Pampanos, A.; Volaki, K.; Kanavakis, E.; Papandreou, O.; Youroukos, S.; Thomaidis, L.; Karkelis, S.; Tzetis, M.; Kitsiou-Tzeli, S. A substitution involving the NLGN4 gene associated with autistic behavior in the Greek population. Genet. Test. Mol. Biomarkers, 2009, 13(5), 611-615. http://dx. doi. org/10. 1089/gtmb. 2009. 0005.
145. Daoud, H.; Bonnet-Brilhault, F.; Vedrine, S.; Demattei, M. V.; Vourc'h, P.; Bayou, N.; Andres, C. R.; Barthelemy, C.; Laumonnier, F.; Briault, S. Autism and nonsyndromic mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level. Biol. Psychiatry, 2009, 66(10), 906-910. http://dx. doi. org/10. 1016/j. biopsych. 2009. 05. 008.
146. Hollander, E.; Bartz, J.; Chaplin, W.; Phillips, A.; Sumner, J.; Soorya, L.; Anagnostou, E.; Wasserman S. Oxytocin increases retention of social cognition in autism. Biol. Psychiatry, 2007, 61(4), 498-503. http://dx. doi. org/10. 1016/j. biopsych. 2006. 05. 030.
147. Anagnostou, E.; Soorya, L.; Chaplin, W.; Bartz, J.; Halpern, D.; Wasserman, S.; Wang, A. T.; Pepa, L.; Tanel, N.; Kushki, A.; Hollander, E. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol. Autism, 2012, 3(1), 16. Epub 2012/12/12. http://dx. doi. org/10. 1186/2040-2392-3-16.
148. Ninan, I. Oxytocin suppresses basal glutamatergic transmission but facilitates activity-dependent synaptic potentiation in the medial prefrontal cortex. J. Neurochem., 2011, 119(2), 324-331. http://dx. doi. org/10. 1111/j. 1471-4159. 2011. 07430. x.
149. Hardan, A. Y.; Jou, R. J.; Handen, B. L. A retrospective assessment of topiramate in children and adolescents with pervasive developmental disorders. J. Child Adolesc. Psychopharmacol., 2004, 14(3), 426-432. http://dx. doi. org/10. 1089/cap. 2004. 14. 426.
150. Rezaei, V.; Mohammadi, M. R.; Ghanizadeh A.; Sahraian A.; Tabrizi, M.; Rezazadeh, S. A.; Akhonzhadeh, S. Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder. Prog. Neuro-psychopharmacol. Biol. Psychiatry, 2010, 34(7), 1269-1272. http://dx. doi. org/10. 1016/j. pnpbp. 2010. 07. 005.
151. Doyle, C. A.; McDougle, C. J. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialog. Clin. Neurosci., 2012, 14(3), 263-279. PubMed ID: 23226952.
152. Berlin, H. A.; Koran, L. M.; Jenike, M. A.; Shapira N. A.; Chaplin, W.; Pallanti, S.; Hollander, E. Double-blind, placebo-controlled trial of topiramate augmentation in treatment-resistant obsessivecompulsive disorder. J. Clin. Psychiatry, 2011, 72(5), 716-721. http://dx. doi. org/10. 4088/JCP. 09m05266gre.
153. Erickson, C. A.; Posey, D. J.; Stigler, K. A.; Mullett, J.; Katschke, A. R.; McDougle, C. J. A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology, 2007, 191(1), 141-147. http://dx. doi. org/10. 1007/s00213-006-0518-9.
154. Owley, T.; Salt, J.; Guter, S.; Grieve, A.; Walton, L.; Ayuyao, N.; Leventhal, B. L.; Cook, E. H. A prospective, open-label trial of memantine in the treatment of cognitive, behavioral, and memory dysfunction in pervasive developmental disorders. J. Child Adolesc. Psychopharmacol., 2006, 16(5), 517-524. http://dx. doi. org/10. 1089/cap. 2006. 16. 517.
155. Chez, M. G.; Burton, Q.; Dowling, T.; Chang, M.; Khanna, P.; Kramer, C. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J. Child Neurol., 2007, 22(5), 574-579. http://dx. doi. org/10. 1177/0883073807302611.
156. Reiser, G.; Binmoller, F. J.; Koch, R. Memantine (1-amino-3, 5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line. Brain Res., 1988, 443(1-2). 338-344. http://dx. doi. org/10. 1016/0006-8993(88)91630-7.
157. Rammes, G.; Rupprecht, R.; Ferrari, U.; Zieglgansberger, W.; Parsons, C. G. The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci. Lett., 2001, 306(1-2), 81-84. http://dx. doi. org/10. 1016/S0304-3940(01)01872-9.
158. Becker, B.; Klein, E. M.; Striepens, N.; Mihov, Y.; Schlaepfer, T. E.; Reul, J.; Goosens, L.; Schruers, K.; Kendrick K. M.; Hurlemann, R. Nicotinic Acetylcholine Receptors Contribute to Learning-induced Metaplasticity in the Hippocampus. J. Cogn. Neurosci., 2013, 25(7), 986-997. http://dx. doi. org/10. 1162/jocna 00383.
159. Seeman, P.; Caruso, C.; Lasaga, M. Memantine agonist action at dopamine D2High receptors. Synapse, 2008, 62(2), 149-153. http://dx. doi. org/10. 1002/syn. 20472.
160. Blanpied, T. A.; Clarke, R. J.; Johnson, J. W. Amantadine inhibits NMDA receptors by accelerating channel closure during channel block. J. Neurosci, 2005, 25(13), 3312-3322. http://dx. doi. org/10. 1523/JNEUROSCI. 4262-04. 2005.
161. King, B. H.; Wright, D. M.; Handen, B. L.; Sikich, L.; Zimmerman, A. W.; McMahon, W.; Cantwell, E.; Davanzo, P. A.; Dourish, C. T.; Dykens, E. M.; Hooper, S. R.; Jaselskis, C. A.; Leventhal, B. L.; Levitt, J.; Lord, C.; Lubetsky, M. J.; Myers, S. M.; Ozonoff, S.; Shah, B. G.; Snape, M.; Shernoff, E. W.; Williamson, K.; Cook, E. H. Jr. Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder. J. Am. Acad. Child Adolesc. Psychiatry, 2001, 40(6), 658-665. http://dx. doi. org/10. 1097/00004583-200106000-00010.
162. Mann, K.; Kiefer, F.; Spanagel, R.; Littleton, J. Acamprosate: recent findings and future research directions. Alcohol. Clin. Exp. Res., 2008, 32(7), 1105-1110. DOI: 10. 1111/j. 1530-0277. 2008. 00690. x.
163. Mason, B. J., Crean, R. Acamprosate in the treatment of alcohol dependence: clinical and economic considerations. Expert Rev. Neurother., 2007, 7(11), 1465-1477. PMID: 17997696.
164. Littleton, J. M. Acamprosate in alcohol dependence: implications of a unique mechanism of action. J. Addict. Med., 2007, 1(3), 115-125. http://dx. doi. org/10. 1097/ADM. 0b013e318156c26f.
165. Erickson, C. A.; Early, M.; Stigler, K. A.; Wink, L. K.; Mullett, J. E.; McDougle, C. J. An open-label naturalistic pilot study of acamprosate in youth with autistic disorder. J. Child Adolesc. Psychopharmacol., 2011, 21(6), 565-569. http://dx. doi. org/10. 1089/cap. 2011. 0034.
166. Erickson C. A.; Wink, L. K.; Ray, B.; Early, M. C.; Stiegelmeyer, E.; Mathieu-Frasier, L.; Patrick, V.; Lahiri, D. K.; McDougle, C. J. Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome. Psychopharmacology, 2013, 228(1), 75-84. http://dx. doi. org/10. 1007/s00213-013-3022-z.
167. Goff, D. C. D-cycloserine: an evolving role in learning and neuroplasticity in schizophrenia. Schizophr. Bull., 2012, 38(5), 936-941. http://dx. doi. org/10. 1093/schbul/sbs012.
168. Posey, D. J.; Kem, D. L.; Swiezy, N. B.; Sweeten, T. L.; Wiegand, R. E.; McDougle, C. J. A pilot study of D-cycloserine in subjects with autistic disorder. Am. J. Psychiatry, 2004, 161(11), 2115-2117. http://dx. doi. org/10. 1176/appi. ajp. 161. 11. 2115.
169. Purcell, A. E.; Jeon, O. H.; Zimmerman, A. W.; Blue, M. E.; Pevsner, J. Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology, 2001, 57(9), 1618-28.
170. Bernardi, S.; Anagnostou, E.; Shen, J.; Kolevzon, A.; Buxbaum, J. D.; Hollander, E.; Hof, P. R.; Fa, J. In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain Res., 2011, 1380, 198-205. http://dx. doi. org/10. 1016/j. brainres. 2010. 12. 057.
171. Rubenstein, J. L.; Merzenich, M. M. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain, Behav., 2003, 2(5), 255-267. PMID: 14606691.
172. Li, J.; Pelletier, M. R.; Perez, V. J. L.; Carlen, P. L. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Mol. Cell. Neurosci., 2002, 19(2), 138-251. http://dx. doi. org/10. 1006/mcne. 2001. 1085.
173. Godfraind, J. M.; Reyniers, E.; De Boulle, K.; D'Hooge, R.; De Deyn, P. P.; Bakker, C. E.; Oostra, B. A.; Kooy, R. F.; Willems, P. J. Long-term potentiation in the hippocampus of fragile X knockout mice. Am. J. Med. Genet., 1996, 64(2), 246-251. http://dx. doi. org/10. 1002/(SICI)1096-8628(19960809)64: 2<246:: AID-AJMG2>3. 0. CO; 2-S.
174. Gocel, J.; Larson, J. Synaptic NMDA receptor-mediated currents in anterior piriform cortex are reduced in the adult fragile X mouse. Neuroscience, 2012, 221, 170-181. http://dx. doi. org/10. 1016/j. neuroscience. 2012. 06. 052.
175. Pilpel, Y.; Kolleker, A.; Berberich, S.; Ginger, M.; Frick, A.; Mientjes, E.; Oostra, B.; Seeburg, P. H. Synaptic ionotropic glutamate receptors and plasticity are developmentally altered in the CA1 field of Fmr1 knockout mice. J. Physiol., 2009, 587(Pt 4), 787-804. http://dx. doi. org/10. 1113/jphysiol. 2008. 160929.
176. Larson, J.; Jessen, R. E.; Kim D.; Fine, A. K.; du Hoffmann, J. Agedependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein. J. Neurosci., 2005, 25(41), 9460-9469. http://dx. doi. org/10. 1523/JNEUROSCI. 2638-05. 2005.
177. Gantois, I.; Pop, A. S.; de Esch, C. E.; Buijsen, R. A.; Pooters, T.; Gomez-Mancilla, B.; Gasparini, F.; Oostra, B. A.; D'Hooge R.; Willemsen, R. Chronic administration of AFQ056/Mavoglurant restores social behaviour in Fmr1 knockout mice. Behav. Brain Res., 2013, 239, 72-79. http://dx. doi. org/10. 1016/j. bbr. 2012. 10. 059.
178. Pop, A. S.; Levenga, J.; de Esch, C. E.; Buijsen R. A.; Nieuwenhuizen, I. M.; Li, T.; Isaacs, A.; Gasparini F.; Oostra B.; Willemsen, R. Rescue of dendritic spine phenotype in Fmr1 KO mice with the mGluR5 antagonist AFQ056/Mavoglurant. Psychopharmacology, 2012. PMID: 23254376.
179. Michalon, A.; Sidorov, M.; Ballard, T. M.; Ozmen, L.; Spooren, W.; Wettstein, J. G.; Jaeschke, G.; Bear, M. F.; Lindemann L. Chronic pharmacological mGlu5 inhibition corrects fragile X in adult mice. Neuron, 2012, 74(1), 49-56. http://dx. doi. org/10. 1016/j. neuron. 2012. 03. 009.
180. Levenga, J.; Hayashi, S.; de Vrij, F. M.; Koekkoek, S. K.; van der Linde, H. C.; Nieuwenhuizen, I.; Song, C.; Buisen, R. A.; Pop, A. S.; Gomez-Mancilla, B.; Nelson, D. L.; Willemsen, R.; Gasparini, F.; Osstra B. A. AFQ056, a new mGluR5 antagonist for treatment of fragile X syndrome. Neurobiol. Dis., 2011, 42(3), 311-317. http://dx. doi. org/10. 1016/j. nbd. 2011. 01. 022.
181. de Vrij, F. M.; Levenga, J.; van der, Linde, H. C.; Koekkoek, S. K.; De Zeeuw, C. I.; Nelson, D. L.; Oostra, B. A.; Willemsen R. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol. Dis., 2008, 31(1), 127-132. http://dx. doi. org/10. 1016/j. nbd. 2008. 04. 002.
182. Silverman, J. L.; Tolu, S. S.; Barkan, C. L.; Crawley, J. N. Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by the mGluR5 antagonist MPEP. Neuropsychopharmacology, 2010, 35(4), 976-989. http://dx. doi. org/10. 1038/npp. 2009. 201.
183. Suvrathan, A.; Hoeffer, C. A.; Wong, H.; Klann, E.; Chattarji, S. Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome. Proc. Natl. Acad. Sci. U. S. A., 2010, 107(25), 11591-11596. http://dx. doi. org/10. 1073/pnas. 1002262107.
184. Wei, H.; Dobkin, C.; Sheikh A. M.; Malik, M.; Brown, W. T.; Li, X. The therapeutic effect of memantine through the stimulation of synapse formation and dendritic spine maturation in autism and fragile X syndrome. PloS One, 2012, 7(5), e36981. http://dx. doi. org/10. 1371/journal. pone. 0036981.
185. Gambrill, A. C. Barria, A. NMDA receptor subunit composition controls synaptogenesis and synapse stabilization. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(14), 5855-5860. http://dx. doi. org/10. 1073/pnas. 1012676108.
186. Barria, A.; Malinow, R. NMDA receptor subunit composition controls synaptic plasticity by regulating binding to CaMKII. Neuron, 2005, 48(2), 289-301. http://dx. doi. org/10. 1016/j. neuron. 2005. 08. 034.
187. Wang, H.; Wu, L. J.; Kim S. S.; Lee, F. J.; Gong, B.; Toyoda, H.; Ren, M.; Shang, Y. Z.; Xu H.; Liu, F.; Zhao, M. G.; Zhuo, M. FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron, 2008, 59(4), 634-47. http://dx. doi. org/10. 1016/j. neuron. 2008. 06. 027.
188. Xu, Z. H.; Yang, Q.; Feng, B.; Liu, S. B.; Zhang, N.; Xing, J. H.; Li, X. Q.; Wu, Y. M.; Gao G. D.; Zhao, M. G. Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome. Mol. Neurodegener., 2012, 7, 24. Epub 2012/05/30. http://dx. doi. org/10. 1186/1750-1326-7-24.
189. Krueger, D. D.; Osterweil, E. K.; Chen, S. P.; Tye, L. D.; Bear M. F. Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome. Proc. Natl. Acad. Sci. USA, 2011, 108(6), 2587-92. http://dx. doi. org/10. 1073/pnas. 1013855108.
190. Yun, S. H.; Trommer, B. L. Fragile X mice: reduced longterm potentiation and N-Methyl-D-Aspartate receptor-mediated neurotransmission in dentate gyrus. J. Neurosci. Res., 2011, 89(2), 176-182. http://dx. doi. org/10. 1002/jnr. 22546.
191. Mientjes, E. J.; Nieuwenhuizen, I.; Kirkpatrick, L.; Zu, T.; Hoogeveen-Westerveld, M.; Severijnen, L.; Rife, M.; Willemsen R.; Nelson D. L.; Oostra, B. A. The generation of a conditional Fmr1 knock out mouse model to study Fmrp function in vivo. Neurobiol. Dis., 2006, 21(3), 549-555. http://dx. doi. org/10. 1016/j. nbd. 2005. 08. 019.
192. Kooy, R. F.; D'Hooge, R.; Reyniers, E.; Bakker, C. E.; Nagels, G.; De Boulle, K.; Storm, K.; Clincke, G.; De Deyn, P. P.; Oostra B. A.; Willems P. J. Transgenic mouse model for the fragile X syndrome. Am. J. Med. Genet., 1996, 64(2), 241-245. http://dx. doi. org/10. 1002/(SICI)1096-8628(19960809)64: 2<241:: AID-AJMG1>3. 0. CO; 2-X.
193. Edbauer, D.; Neilson, J. R.; Foster, K. A.; Wang C. F.; Seeburg, D. P.; Batterton, M. N.; Tada, T.; Dolan, B. M.; Sharp, P. A.; Sheng, M. Regulation of synaptic structure and function by FMRPassociated microRNAs miR-125b and miR-132. Neuron, 2010, 65(3), 373-384. http://dx. doi. org/10. 1016/j. neuron. 2010. 01. 005.
194. Zhu T.; Uzunova G.; Cohen I. J.; Musnier A.; D'Hulst C.; Ng M.; Drouet V.; Dictenberg J. Altered early synaptic glutamate receptor expression through FMRP-dependent translational CAM mRNA regulation. Society for Neuroscience Annual Meeting, October 13-17, New Orleans, LA., 2012.
195. Hu, H.; Qin, Y.; Bochorishvili G.; Zhu, Y.; van Aelst, L.; Zhu, J. J. Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. J. Neurosci., 2008, 28(31), 7847-7862. http://dx. doi. org/10. 1523/JNEUROSCI. 1496-08. 2008.
196. Kaufmann, W. E.; Abrams, M. T.; Chen, W.; Reiss, A. L. Genotype, molecular phenotype, and cognitive phenotype: correlations in fragile X syndrome. Am. J. Med. Genet., 1999, 83(4), 286-295. http://dx. doi. org/10. 1002/(SICI)1096-8628(19990402)83: 4<286:: AID-AJMG10>3. 0. CO; 2-H.
197. Hagerman, R.; Au, J.; Hagerman P. FMR1 premutation and full mutation molecular mechanisms related to autism. J. Neurodev. Disord., 2011, 3(3), 211-224. http://dx. doi. org/10. 1007/s11689-011-9084-5.
198. Hessl, D.; Wang, J. M.; Schneider, A.; Koldewyn, K.; Le, L.; Iwahashi, C.; Cheung, K.; Tassone F.; Hagerman P. J.; Rivera, S. M. Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biol. Psychiatry, 2011, 70(9), 859-865. http://dx. doi. org/10. 1016/j. biopsych. 2011. 05. 033.
199. Kron, M.; Howell, C. J.; Adams, I. T.; Ransbottom, M.; Christian, D.; Ogier, M.; Katz, D. M. Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment. J. Neurosci., 2012, 32(40), 13860-13872. http://dx. doi. org/10. 1523/JNEUROSCI. 2159-12. 2012.
200. Nguyen, M. V.; Du, F.; Felice C. A.; Shan, X.; Nigam, A.; Mandel, G.; Robinson, J. K.; Ballas N. MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain. J. Neurosci., 2012, 32(29), 10021-10034. http://dx. doi. org/10. 1523/JNEUROSCI. 1316-12. 2012.
201. Bateup, H. S.; Takasaki, K. T.; Saulnier, J. L.; Denefrio, C. L.; Sabatini B. L. Loss of Tsc1 in vivo impairs hippocampal mGluRLTD and increases excitatory synaptic function. J. Neurosci., 2011, 31(24), 8862-8869. 10. 1523/JNEUROSCI. 1617-11.
202. Pfeiffer, B. E.; Huber, K. M. The state of synapses in fragile X syndrome. Neuroscientist, 2009, 15(5), 549-567. http://dx. doi. org/10. 1177/1073858409333075.
203. Jacome, L. F.; Burket, J. A.; Herndon, A. L.; Deutsch, S. I. Genetically inbred Balb/c mice differ from outbred Swiss Webster mice on discrete measures of sociability: relevance to a genetic mouse model of autism spectrum disorders. Autism Res., 2011, 4(6), 393-400. http://dx. doi. org/10. 1002/aur. 218.
204. Deutsch, S. I.; Pepe, G. J.; Burket, J. A.; Winebarger, E. E.; Herndon A. L.; Benson, A. D. D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice. Brain Res., 2012, 1439, 96-107. http://dx. doi. org/10. 1016/j. brainres. 2011. 12. 040.
205. Burket, J. A.; Herndon, A. L.; Winebarger, E. E.; Jacome, L. F.; Deutsch, S. I. Complex effects of mGluR5 antagonism on sociability and stereotypic behaviors in mice: possible implications for the pharmacotherapy of autism spectrum disorders. Brain Res. Bull., 2011, 86(3-4), 152-158. http://dx. doi. org/10. 1016/j. brainresbull. 2011. 08. 001.
206. Saunders, J. A.; Gandal, M. J.; Roberts, T. P.; Siegel, S. J. NMDA antagonist MK801 recreates auditory electrophysiology disruption present in autism and other neurodevelopmental disorders. Behav. Brain Res., 2012, 234(2), 233-237. http://dx. doi. org/10. 1016/j. bbr. 2012. 06. 032.
207. Gandal, M. J.; Sisti, J.; Klook, K.; Ortinski, P. I.; Leitman, V.; Liang, Y.; Thieu, T.; Anderson, R.; Pierce, R. C.; Jonak, G.; Gur, R. E.; Carlson, G.; Siegel, S. J. GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Transl. Psychiatry, 2012, 2, e142. Epub 2012/07/19. http://dx. doi. org/10. 1038/tp. 2012. 69.
208. Gandal, M. J.; Anderson, R. L.; Billingslea, E. N.; Carlson, G. C.; Roberts T. P.; Siegel, S. J. Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia? Genes Brain Behav., 2012, 11(6), 740-750. http://dx. doi. org/10. 1111/j. 1601-183X. 2012. 00816. x.
209. Saunders, J. A.; Tatard-Leitman, V. M.; Suh, J.; Billingslea, E. N.; Roberts, T. P.; Siegel, S. J. Knockout of NMDA Receptors in Parvalbumin Interneurons Recreates Autism-Like Phenotypes. Autism Res., 2013. Epub 2013/02/27. http://dx. doi. org/10. 1002/aur. 1264.
210. Henderson, C.; Wijetunge L.; Kinoshita, M. N.; Shumway, M.; Hammond, R. S.; Postma F. R.; Brynzska, C.; Rush, R.; Thomas, A.; Paylor, A.; Warren S. T.; Vanderklish, P. W.; Kind, P. C.; Carpenter R. L.; Bear, M. F.; Healy, A. M. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABA(B) receptors with arbaclofen. Science Transl. Med., 2012, 4(152), 152ra28. Epub 2012/09/21. http://dx. doi. org/10. 1126/scitranslmed. 3004218.
211. Hagerman, R.; Lauterborn, J.; Au, J.; Berry-Kravis, E. Fragile X syndrome and targeted treatment trials. Res. Probl. Cell Differ., 2012, 54, 297-335. http://dx. doi. org/10. 1007/978-3-642-21649-7-17.
212. Corbett, B. A.; Schupp, C. W.; Lanni, K. E. Comparing biobehavioral profiles across two social stress paradigms in children with and without autism spectrum disorders. Mol. Autism, 2012, 3(1), 13. Epub 2012/11/20. http://dx. doi. org/10. 1186/2040-2392-3-13.
213. Anderson, C. J.; Colombo, J.; Unruh, K. E. Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder. Dev. Psychobiol., 2013, 55(5), 465-482. http://dx. doi. org/10. 1002/dev. 21051.
214. Wisbeck, J. M.; Huffman, L. C.; Freund, L.; Gunnar, M. R.; Davis, E. P.; Reiss, A. L. Cortisol and social stressors in children with fragile X: a pilot study. J. Dev. Behav. Pediatr., 2000, 21(4), 278-282. http://dx. doi. org/10. 1097/00004703-200008000-00004.
215. Hessl, D.; Glaser, B.; Dyer-Friedman, J.; Blasey, C.; Hastie, T.; Gunnar, M.; Reiss, A. L. Cortisol and behavior in fragile X syndrome. Psychoneuroendocrinology, 2002, 27(7), 855-872. http://dx. doi. org/10. 1016/S0306-4530(01)00087-7.
216. Markham, J. A.; Beckel-Mitchener, A. C.; Estrada, C. M.; Greenough, W. T. Corticosterone response to acute stress in a mouse model of Fragile X syndrome. Psychoneuroendocrinology, 2006, 31(6), 781-785. http://dx. doi. org/10. 1016/j. psyneuen. 2006. 02. 008.
217. Qin, M.; Entezam, A.; Usdin, K.; Huang, T.; Liu, Z. H.; Hoffman, G. E.; Smith, C. B. A mouse model of the fragile X premutation: effects on behavior, dendrite morphology, and regional rates of cerebral protein synthesis. Neurobiol. Dis., 2011, 42(1), 85-98. http://dx. doi. org/10. 1016/j. nbd. 2011. 01. 008.
218. Caudal, D.; Godsil, B. P.; Mailliet, F.; Bergerot, D.; Jay, T. M. Acute stress induces contrasting changes in AMPA receptor subunit phosphorylation within the prefrontal cortex, amygdala and hippocampus. PloS One, 2010, 5(12), e15282. http://dx. doi. org/10. 1371/journal. pone. 0015282.
219. Schmidt, M. V.; Trumbach, D.; Weber, P.; Wagner, K.; Scharf, S. H.; Liebl, C.; Datson, N.; Namendorf, C.; Gerlach, T.; Kuhne, C.; Uhr, M.; Deussing, J. M.; Wurst, W.; Binder, E. B.; Holsboer, F.; Muller, M. B. Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus. J. Neurosci., 2010, 30(50), 16949-16958. http://dx. doi. org/10. 1523/JNEUROSCI. 4668-10. 2010.
220. Fumagalli, F.; Caffino L.; Vogt, M. A.; Frasca, A.; Racagni, G.; Sprengel, R.; Gass, P.; Riva, M. AMPA GluR-A receptor subunit mediates hippocampal responsiveness in mice exposed to stress. Hippocampus, 2011, 21(9), 1028-1035. 10. 1002/hipo. 20817.
221. Conboy, L.; Sandi, C. Stress at learning facilitates memory formation by regulating AMPA receptor trafficking through a glucocorticoid action. Neuropsychopharmacology, 2010, 35(3), 674-685. http://dx. doi. org/10. 1038/npp. 2009. 172.
222. Martin, S.; Henley, J. M.; Holman, D.; Zhou, M.; Wiegert, O.; van Spronsen, M.; Joels, M.; Hoogenraad, C. C.; Krugers, H. J. Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity. PloS One, 2009, 4(3), 5. http://dx. doi. org/10. 1371/journal. pone. 0004714.
223. Hazlett, H. C.; Poe, M. D.; Lightbody, A. A.; Styner, M.; MacFall, J. R.; Reiss, A. L.; Piven, J. Trajectories of early brain volume development in fragile X syndrome and autism. J. Am. Acad. Child Adolesc. Psychiatry, 2012, 51(9), 921-33. http://dx. doi. org/10. 1016/j. jaac. 2012. 07. 003.
224. Steinlin, M. The cerebellum in cognitive processes: supporting studies in children. Cerebellum, 2007, 6(3), 237-241. http://dx. doi. org/10. 1080/14734220701344507.
225. Huber, K. M. The fragile X-cerebellum connection. Trends Neurosci., 2006, 29(4), 183-185. http://dx. doi. org/10. 1016/j. tins. 2006. 02. 001.
226. Giza, J.; Urbanski, M. J.; Prestori, F.; Bandyopadhyay, B.; Yam, A.; Friedrich, V.; Kelley, K.; D'Angelo, E.; Goldfarb, M. Behavioral and cerebellar transmission deficits in mice lacking the autismlinked gene islet brain-2. J. Neurosci., 2010, 30(44), 14805-14816. http://dx. doi. org/10. 1523/JNEUROSCI. 1161-10. 2010.
227. Safo, P. K.; Regehr, W. G. Endocannabinoids control the induction of cerebellar LTD. Neuron, 2005, 48(4), 647-659. PMID: 16301180.
228. Carey M. R.; Myoga M. H.; McDaniels K. R.; Marsicano G.; Lutz B.; Mackie K.; Regher W. G. Presynaptic CB1 receptors regulate synaptic plasticity at cerebellar parallel fiber synapses. J. Neurophysiology, 2011, 105(2), 958-963. http://dx. doi. org/10. 1152/jn. 00980. 2010.
229. Bear, M. F.; Huber, K. M.; Warren, S. T. The mGluR theory of fragile X mental retardation. Trends Neurosci., 2004, 27(7), 370-377. http://dx. doi. org/10. 1016/j. tins. 2004. 04. 009.
230. Park, S.; Park, J. M.; Kim, S.; Kim J. A.; Shepherd J. D.; Smith-Hicks C. L.; Chowdhury, S.; Kaufmann, W.; Kuhl, D.; Ryazanov, A. G.; Huganir, R. L.; Linden, D. J.; Worley, P. F. Elongation factor 2 and fragile X mental retardation protein control the dynamic translation of Arc/Arg3. 1 essential for mGluR-LTD. Neuron, 2008, 59(1), 70-83. http://dx. doi. org/10. 1016/j. neuron. 2008. 05. 023.
231. Garber, K. B.; Visootsak, J.; Warren, S. T. Fragile X syndrome. Eur. J. Hum. Genet., 2008, 16(6), 666-672. http://dx. doi. org/10. 1038/ejhg. 2008. 61.
232. Waung, M. W.; Huber, K. M. Protein translation in synaptic plasticity: mGluR-LTD, Fragile X. Curr. Opin. Neurobiol., 2009, 19(3), 319-326. http://dx. doi. org/10. 1016/j. conb. 2009. 03. 011.
233. Luscher, C.; Huber, K. M. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron, 2010, 65(4), 445-459. http://dx. doi. org/10. 1016/j. neuron. 2010. 01. 016.
234. Nakamoto, M.; Nalavadi, V.; Epstein, M. P.; Narayanan, U.; Bassell, G. J.; Warren, S. T. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc. Natl. Acad. Sci. U. S. A., 2007, 104(39), 15537-15542. http://dx. doi. org/10. 1073/pnas. 0707484104.
235. Nosyreva, E. D.; Huber, K. M. Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. J. Neurophysiol., 2006, 95(5), 3291-3295. http://dx. doi. org/10. 1152/jn. 01316. 2005.
236. Davidkova, G.; Ng, M.; Wu, H.; Drouet, V.; D'Hulst, C.; Dictenberg, G.; Altered activity-induced neuroligin translation and synapse homeostasis in Fragile X syndrome, Society for Neuroscience Annual Meeting, November 12-16; Washington, D. C., 2011.
237. Isaac, J. T.; Ashby, M. C.; McBain, C. J. The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron, 2007, 54(6), 859-871. http://dx. doi. org/10. 1016/j. neuron. 2007. 06. 001.
238. Zhang, Y.; Venkitaramani, D. V.; Gladding, C. M.; Zhang, Y.; Kurup, P.; Molnar, E.; Collingridge, G. L.; Lombroso, P. J. The tyrosine phosphatase STEP mediates AMPA receptor endocytosis after metabotropic glutamate receptor stimulation. J. Neurosci., 2008, 28(42), 10561-10566. http://dx. doi. org/10. 1523/JNEUROSCI. 2666-08. 2008.
239. Hou, L.; Antion, M. D.; Hu, D.; Spencer, C. M.; Paylor, R.; Klann, E. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron, 2006, 51(4), 441-454. http://dx. doi. org/10. 1016/j. neuron. 2006. 07. 005.
240. Lu, R.; Wang, H.; Liang, Z.; Ku, L.; O'Donnell, W. T.; Li, W.; Warren S. T.; Feng, Y. The fragile X protein controls microtubuleassociated protein 1B translation and microtubule stability in brain neuron development. Proc. Natl. Acad. Sci. U. S. A., 2004, 101(42), 15201-15206. http://dx. doi. org/10. 1073/pnas. 0404995101.
241. Johnson, M. A.; Lombroso, P. J. A common STEP in the synaptic pathology of diverse neuropsychiatric disorders. Yale J. Biol. Med., 2012, 85(4), 481-490. PMID: 23239949.
242. Goebel-Goody, S. M.; Baum, M.; Paspalas, C. D.; Fernandez, S. M.; Carty, N. C.; Kurup, P.; Lombroso P. J. Therapeutic implications for striatal-enriched protein tyrosine phosphatase (STEP) in neuropsychiatric disorders. Pharmacol. Rev., 2012, 64(1), 65-87. http://dx. doi. org/10. 1124/pr. 110. 003053.
243. Goebel-Goody, S. M.; Wilson-Wallis, E. D.; Royston, S.; Tagliatela, S. M.; Naegele, J. R.; Lombroso, P. J. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain Behav., 2012, 11(5), 586-600. http://dx. doi. org/10. 1111/j. 1601-183X. 2012. 00781. x.
244. Muddashetty, R. S.; Kelic, S.; Gross, C.; Xu, M.; Bassell, G. J. Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome. J. Neurosci., 2007, 27(20), 5338-5348. http://dx. doi. org/10. 1523/JNEUROSCI. 0937-07. 2007.
245. Nalavadi, V. C.; Muddashetty, R. S.; Gross, C.; Bassell, G. J. Dephosphorylation-induced ubiquitination and degradation of FMRP in dendrites: a role in immediate early mGluR-stimulated translation. J. Neurosci., 2012, 32(8), 2582-2587. PMID: 22357842.
246. Greer, P. L.; Hanayama, R.; Bloodgood, B. L.; Mardinly, A. R.; Lipton, D. M.; Flavell, S. W.; Kim, T. K.; Griffith, T. C.;. Waldon, Z.; Maehr, R.; Pleogh, H. L.; Chowdhury, S.; Worley, P. F.; Steen, J.; Greenberg M. E. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell, 2010, 140(5), 704-716. http://dx. doi. org/10. 1016/j. cell. 2010. 01. 026.
247. Bateup, H. S.; Johnson, C. A.; Denefrio, C. L.; Saulnier, J. L.; Kornacker, K.; Sabatini, B. L. Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron, 2013, 78(3), 510-522. http://dx. doi. org/10. 1016/j. neuron. 2013. 03. 017.
248. Liu, S. J.; Zukin, R. S. Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. Trends Neurosci., 2007, 30(3), 126-134. PMID: 17275103.
249. Grooms, S. Y.; Opitz, T.; Bennett, M. V.; Zukin, R. S. Status epilepticus decreases glutamate receptor 2 mRNA and protein expression in hippocampal pyramidal cells before neuronal death. Proc. Natl. Acad. Sci. U. S. A., 2000, 97(7), 3631-3636. http://dx. doi. org/10. 1073/pnas. 97. 7. 3631.
250. Hu, Y.; Jiang, L.; Chen, H.; Zhang, X. Expression of AMPA receptor subunits in hippocampus after status convulsion. Child's Nerv. Syst., 2012, 28(6), 911-918. http://dx. doi. org/10. 1007/s00381-012-1747-3.
251. Rogawski, M. A. AMPA receptors as a molecular target in epilepsy therapy. Acta Neurol. Scand. Suppl., 2013, (197), 9-18. http://dx. doi. org/10. 1111/ane. 12099.
252. Lanore, F.; Labrousse, V. F.; Szabo, Z.; Normand, E.; Blanchet, C.; Mulle, C. Deficits in morphofunctional maturation of hippocampal mossy fiber synapses in a mouse model of intellectual disability. J. Neurosci., 2012, 32(49), 17882-17893. http://dx. doi. org/10. 1523/JNEUROSCI. 2049-12. 2012.
253. Strutz-Seebohm, N.; Korniychuk, G.; Schwarz, R.; Baltaev, R.; Ureche, O. N.; Mack, A. F.; Ma, Z. L.; Hollman, M.; Lang, F.; Seebohm, G. Functional significance of the kainate receptor GluR6(M836I) mutation that is linked to autism. Cell. Physiol. Biochem., 2006, 18(4-5), 287-294. http://dx. doi. org/10. 1159/000097675.
254. Gauthier, J.; Siddiqui, T. J.; Huashan, P.; Yokomaku, D.; Hamdan, F. F.; Champagne, N.; Lapointe, M.; Spiegelman, D.; Noreau, A,; Lafreniere R. G.; Fathalli, F.; Joober, R.; Krebs, M. O.; DeLisi, L. E.; Mottron, L.; Fombonne, E.; Michaud, J. L.; Drapeau, P.; Carbonetto S.; Craig, A. M.; Rouleau, G. A. Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia. Hum. Genet., 2011, 130(4), 563-73. http://dx. doi. org/10. 1007/s00439-011-0975-z.
255. Sato, D.; Lionel, A. C.; Leblond C. S.; Prasad A.; Pinto, D.; Walker, S.; O'Connor, I.; Russel, C.; Drmic, I. E.; Hamdan, F. F.; Michaud, J. L.; Endris, V.; Roeth, R.; Delorme, R.; Huguet, G.; Leboyer, M.; Rastam, M.; Gillberg C.; Lathrop M.; Stavropolous, D. J.; Anagnostou, E.; Weksberg, R.; Fombonne, E.; Zwaigenbaum L.; Fernandez, B. A.; Roberts W.; Rappold, G. A.; Marshall, C. R.; Bourgeron, T.; Szatmari P.; Scherer, S. W. SHANK1 Deletions in Males with Autism Spectrum Disorder. Am. J. Hum. Genet., 2012, 90(5), 879-887. http://dx. doi. org/10. 1016/j. ajhg. 2012. 03. 017.
256. Jiang, Y. H.; Ehlers, M. D. Modeling autism by SHANK gene mutations in mice. Neuron, 2013, 78(1), 8-27. http://dx. doi. org/10. 1016/j. neuron. 2013. 03. 016.
257. Etherton, M. R.; Tabuchi, K.; Sharma, M.; Ko, J.; Sudhof, T. C. An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus. EMBO J., 2011, 30(14), 2908-2919. http://dx. doi. org/10. 1038/emboj. 2011. 182.
258. Etherton, M.; Foldy, C.; Sharma, M.; Tabuchi, K.; Liu, X.; Shamloo M.; Malenka, R. C.; Sudhof, T. C. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(33), 13764-13769. http://dx. doi. org/10. 1073/pnas. 1111093108.
259. Chih, B.; Engelman, H.; Scheiffele, P. Control of excitatory and inhibitory synapse formation by neuroligins. Science, 2005, 307(5713), 1324-1328. http://dx. doi. org/10. 1126/science. 1107470.
260. Soler-Llavina, G. J.; Fuccillo, M. V.; Ko, J.; Sudhof, T. C.; Malenka, R. C. The neurexin ligands, neuroligins and leucine-rich repeat transmembrane proteins, perform convergent and divergent synaptic functions in vivo. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(40), 16502-16509. http://dx. doi. org/10. 1073/pnas. 1114028108.
261. Siddiqui, T. J.; Pancaroglu, R.; Kang, Y.; Rooyakkers, A.; Craig, A. M. LRRTMs and neuroligins bind neurexins with a differential code to cooperate in glutamate synapse development. J. Neurosci., 2010, 30(22), 7495-7506. http://dx. doi. org/10. 1523/JNEUROSCI. 0470-10. 2010.
262. Ko, J.; Fuccillo, M. V.; Malenka, R. C.; Sudhof, T. C. LRRTM2 functions as a neurexin ligand in promoting excitatory synapse formation, Neuron, 2009, 64(6), 791-8. http://dx. doi. org/10. 1016/j. neuron. 2009. 12. 012.
263. Fu, Z.; Vicini, S. Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells. Mol. Cell. Neurosci., 2009, 42(1), 45-55. http://dx. doi. org/10. 1016/j. mcn. 2009. 05. 004.
264. Budreck, E. C.; Scheiffele, P. Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses. Eur. J. Neurosci., 2007, 26(7), 1738-1748. http://dx. doi. org/10. 1111/j. 1460-9568. 2007. 05842. x.
265. Hoon, M.; Soykan, T.; Falkenburger, B.; Hammer, M.; Patrizi, A.; Schmidt, K. F.; Sassoe-Pognetto, M.; Lowel, S.; Moser T.; Taschenberger, H.; Brose, N.; Varoqueaux, F. Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina. Proc. Natl. Acad. Sci. U. S. A., 2011, 108(7), 3053-3058. http://dx. doi. org/10. 1073/pnas. 1006946108.
266. Baudouin, S. J.; Gaudias, J.; Gerharz, S.; Hatstatt, L.; Zhou, K.; Punnakkal, P.; Tanaka K. F.; Spooren W.; Hen, R.; De Zeewuv, C. I.; Vogt, K.; Scheiffele, P. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science, 2012, 338(6103), 128-132. http://dx. doi. org/10. 1126/science. 1224159.
267. Nam, C. I.; Chen, L. Postsynaptic assembly induced by neurexinneuroligin interaction and neurotransmitter. Proc. Natl. Acad. Sci. U. S. A., 2005, 102(17), 6137-6142. http://dx. doi. org/10. 1073/pnas. 0502038102.
268. Heine, M.; Thoumine, O.; Mondin, M.; Tessier, B.; Giannone, G.; Choquet, D. Activity-independent and subunit-specific recruitment of functional AMPA receptors at neurexin/neuroligin contacts. Proc. Natl. Acad. Sci. USA, 2008, 105(52), 20947-20952.
269. Mondin, M.; Labrousse, V.; Hosy, E.; Heine, M.; Tessier, B.; Levet, F.; Poujol, C.; Blanchet, C.; Choquet, D.; Thoumine O. Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds. J. Neurosci., 2011, 31(38), 13500-13515. http://dx. doi. org/10. 1523/JNEUROSCI. 6439-10. 2011.
270. Zeidan, A.; Ziv, N. E. Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses. PloS One, 2012, 7(7), e42314. http://dx. doi. org/10. 1371/journal. pone. 0042314.
271. Ripley, B.; Otto, S.; Tiglio, K.; Williams, M. E.; Ghosh, A. Regulation of synaptic stability by AMPA receptor reverse signaling. Proc. Natl. Acad. Sci. USA, 2011, 108(1), 367-372. http://dx. doi. org/10. 1073/pnas. 1015163108.
272. Shipman, S. L.; Nicoll, R. A. A subtype-specific function for the extracellular domain of neuroligin 1 in hippocampal LTP. Neuron, 2012, 76(2), 309-16. http://dx. doi. org/10. 1016/j. neuron. 2012. 07. 024.
273. Budreck, E. C.; Kwon, O. B.; Jung J. H.; Baudouin S.; Thommen A.; Kim, H. S.; Fukazawa, Y.; Harada H.; Tabuchi K.; Shigemoto R.; Scheiffele P.; Kim J. H. Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling. Proc. Natl. Acad. Sci. USA, 2013, 110(2), 725-730. http://dx. doi. org/10. 1073/pnas. 1214718110.
274. Dahlhaus, R.; Hines, R. M.; Eadie, B. D.; Kannangara, T. S.; Hines, D. J.; Brown, C. E.; Christie, B. R.; El-Husseini A. Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus. Hippocampus, 2010, 20(2), 305-322. http://dx. doi. org/10. 1002/hipo. 20630.
275. Dahlhaus, R.; El-Husseini, A. Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome. Behav. Brain Res., 2010, 208(1), 96-105. http://dx. doi. org/10. 1016/j. bbr. 2009. 11. 019.
276. Blundell, J.; Blaiss C. A.; Etherton, M. R.; Espinosa, F.; Tabuchi, K.; Walz, C.; Bolliger, M. F.; Sudhof, T. C.; Powell, C. M. Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior. J. Neurosci., 2010, 30(6), 2115-2129. http://dx. doi. org/10. 1523/JNEUROSCI. 4517-09. 2010.
277. Peixoto, R. T.; Kunz, P. A.; Kwon, H.; Mabb, A. M.; Sabatini, B. L.; Philpot, B. D.; Ehlers M. D. Transsynaptic signaling by activitydependent cleavage of neuroligin-1. Neuron, 2012, 76(2), 396-409. http://dx. doi. org/10. 1016/j. neuron. 2012. 07. 006.
278. Boeckers, T. M.; Bockmann, J.; Kreutz, M. R.; Gundelfinger, E. D. ProSAP/Shank proteins-a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J. Neurochem., 2002, 81(5), 903-910. http://dx. doi. org/10. 1046/j. 1471-4159. 2002. 00931. x.
279. Arons, M. H.; Thynne, C. J.; Grabrucker, A. M.; Li, D.; Schoen, M.; Cheyne, J. E.; Boeckers, T. M.; Montgomery, J. M.; Garner, C. C. Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission and neurexin-neuroligin-mediated transsynaptic signaling. J. Neurosci., 2012, 32(43), 14966-14978. http://dx. doi. org/10. 1523/JNEUROSCI. 2215-12. 2012.
280. Schmeisser, M. J.; Ey, E.; Wegener, S.; Bockmann, J.; Stempel, A. V.; Kuebler A.; Janssen A. L.; Udvardi P. T.; Shiban, E.; Spiker, C.; Balschun, D.; Skryabin, B. V.; Dieck, St.; Smalla, K. H.; Montag, D.; Leblond, C. S.; Faure, P.; Tourquet, N.; Le Sourd, A. M.; Toro R.; Grabrucker, A. M.; Shoichet, S. A.; Schmitz, D.; Kreutz, M. R.; Bourgeron, T.; Gundelfinger, E. D.; Boeckers, T. M. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature, 2012, 486(7402), 256-260. 10. 1038/nature11015.
281. Won, H.; Lee, H. R.; Gee, H. Y.; Mah, W.; Kim, J. I.; Lee, J.; Ha, S.; Chung, C.; Jung, E. S.; Cho, Y. S.; Park S. G.; Lee, J. S.; Lee, K.; Kim D.; Bae, Y. C.; Kaang, B. K.; Lee, M. G.; Kim, E. Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature, 2012, 486(7402), 261-265. http://dx. doi. org/10. 1038/nature11208.
282. Gong, X.; Jiang, Y. W.; Zhang, X.; An, Y.; Zhang, J.; Wu Y.; Wang, J.; Sun, Y.; Liu, Y.; Gao, X; Shen, Y.; Wu, X.; Qiu Z.; Jin, L.; Wu, B. L.; Wang, H. High proportion of 22q13 deletions and SHANK3 mutations in Chinese patients with intellectual disability. PloS One, 2012, 7(4), e34739. http://dx. doi. org/10. 1371/journal. pone. 0034739.
283. Phelan, K.; McDermid, H. E. The 22q13. 3 Deletion Syndrome (Phelan-McDermid Syndrome). Mol. Syndromol., 2012, 2(3-5), 186-201. http://dx. doi. org/10. 1159/000334260.
284. Bozdagi, O.; Sakurai, T.; Papapetrou, D.; Wang, X.; Dickstein, D. L.; Takahashi, N.; Kajiwara, Y.; Wang, M.; Katz, A. M.; Scattoni, M. L.; Harris M. J.; Saxena, R.; Silverman, J. L.; Crawley, J. N.; Zhou, Q.; Hof, P. R.; Buxbaum, J. D. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol. Autism, 2010, 1(1), 15. Epub 2010/12/21. http://dx. doi. org/10. 1186/2040-2392-1-15.
285. Wang, X.; McCoy, P. A.; Rodriguiz, R. M.; Pan, Y.; Je, H. S.; Roberts A. C.; Kim C. J.; Berrios, J.; Colvin J. S.; Bousquet-Moore D.; Lorenzo, I.; Wu, G.; Weinberg, R. J.; Ehlers, M. D.; Philpot, B. D.; Beaudet, A. L.; Wetsel, W. C.; Jiang, Y. H. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet., 2011, 20(15), 3093-3108. http://dx. doi. org/10. 1073/pnas. 0804007106.
286. Xia, J.; Chung, H. J.; Wihler, C.; Huganir, R. L.; Linden, D. J. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron, 2000, 28(2), 499-510. http://dx. doi. org/10. 1016/S0896-6273(00)00128-8.
287. Marsden, K. C.; Beattie, J. B.; Friedenthal, J.; Carroll, R. C. NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABA(A) receptors. J. Neurosci., 2007, 27(52), 14326-14337. http://dx. doi. org/10. 1523/JNEUROSCI. 4433-07. 2007.
288. Ma, D. Q.; Cuccaro, M. L.; Jaworski, J. M.; Haynes, C. S.; Stephan, D. A.; Parod, J.; Abramson, R. K.; Wright, H. H.; Gilbert, J. R.; Haines, J. L.; Pericak-vance, M. A. Dissecting the locus heterogeneity of autism: significant linkage to chromosome 12q14. Mol. Psychiatry, 2007, 12(4), 376-84. http://dx. doi. org/10. 1038/sj. mp. 4001927.