Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism

Neuroscience and Biobehavioral Reviews

Volumn 46, Issue P2, 2014, Pages 228-241

  D'Antoni, Simona ^a   Spatuzza, Michela ^a   Bonaccorso, Carmela M ^b   Musumeci, Sebastiano A ^b   Ciranna, Lucia ^c   Nicoletti, Ferdinando ^d,e   Huber, Kimberly M ^f   Catania, Maria Vincenza ^a,b  

^a INSTITUTE OF NEUROLOGICAL SCIENCES   (Italy)

^b OASI RESEARCH INSTITUTE IRCCS   (Italy)

^c UNIVERSITY OF CATANIA   (Italy)

^d IRCCS NEUROMED   (Italy)

^e SAPIENZA UNIVERSITY OF ROME   (Italy)

^f UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Developmental disorders; Fmrp; Fragile X; Homer; Mental retardation; Neuroligin; PTEN; SAPAP3; SHANK; Synaptic plasticity; TSC

Indexed keywords

ENDOCANNABINOID; MESSENGER RNA; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 5; SCAFFOLD PROTEIN; METABOTROPIC GLUTAMATE RECEPTOR TYPE 1; METABOTROPIC RECEPTOR;

AUTISM; CHROMOSOME DELETION; CHROMOSOME DELETION 22Q13; DEVELOPMENTAL DISORDER; DISEASE ASSOCIATION; FRAGILE X SYNDROME; HUMAN; INTELLECTUAL IMPAIRMENT; MACROCEPHALY; NEOCORTEX; NERVE CELL NETWORK; NERVE CELL PLASTICITY; NEUROMODULATION; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; PHENOTYPE; PREFRONTAL CORTEX; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; ANIMAL; METABOLISM;

ANIMALS; AUTISTIC DISORDER; FRAGILE X SYNDROME; HUMANS; INTELLECTUAL DISABILITY; NEURONAL PLASTICITY; RECEPTOR, METABOTROPIC GLUTAMATE 5; RECEPTORS, METABOTROPIC GLUTAMATE; SIGNAL TRANSDUCTION;

EID: 84909978372     PISSN: 01497634     EISSN: 18737528     Source Type: Journal    
DOI: 10.1016/j.neubiorev.2014.02.003     Document Type: Review

References (187)

1. Abrahams B.S., Geschwind D.H. Advances in autism genetics: on the threshold of a new neurobiology. Nat. Rev. Genet. 2008, 9:341-355.
2. Alagarsamy S., Marino M.J., Rouse S.T., Gereau R.W., Heinemann S.F., Conn P.J. Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat. Neurosci. 1999, 2(3):234-240.
3. Alagarsamy S., Saugstad J., Warren L., Mansuy I.M., Gereau R.W., Conn P.J. NMDA-induced potentiation of mGluR5 is mediated by activation of protein phosphatase 2B/calcineurin. Neuropharmacology 2005, 49(1):135-145.
4. Ango F., Prézeau L., Muller T., Tu J.C., Xiao B., Worley P.F., Pin J.P., Bockaert J., Fagni L. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 2001, 411(6840):962-965.
5. Asrar S., Jia Z. Molecular mechanisms coordinating functional and morphological plasticity at the synapse: role of GluA2/N-cadherin interaction-mediated actin signaling in mGluR-dependent LTD. Cell Signal. 2013, 25(2):397-402.
6. Attucci S., Carlà V., Mannaioni G., Moroni F. Activation of type 5 metabotropic glutamate receptors enhances NMDA responses in mice cortical wedges. Br. J. Pharmacol. 2001, 132(4):799-806.
7. Auerbach B.D., Osterweil E.K., Bear M.F. Mutations causing syndromic autism define an axis of synaptic pathophysiology. Nature 2011, 480(7375):63-68.
8. Awad H., Hubert G.W., Smith Y., Levey A.I., Conn P.J. Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J. Neurosci. 2000, 20(21):7871-7879.
9. Bassell G.J., Warren S.T. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 2008, 60(2):201-214.
10. Bateup H.S., Takasaki K.T., Saulnier J.L., Denefrio C.L., Sabatini B.L. Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function. J. Neurosci. 2011, 31(24):8862-8869.
11. Baude A., Nusser Z., Roberts J.D., Mulvihill E., McIlhinney R.A., Somogyi P. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 1993, 11(4):771-787.
12. Baudouin S.J., Gaudias J., Gerharz S., Hatstatt L., Zhou K., Punnakkal P., Tanaka K.F., Spooren W., Hen R., De Zeeuw C.I., Vogt K., Scheiffele P. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science 2012, 338(6103):128-132.
13. Berg A.T., Plioplys S. Epilepsy and autism: is there a special relationship?. Epilepsy Behav. 2012, 23:193-198.
14. 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.
15. Bertaso F., Roussignol G., Worley P., Bockaert J., Fagni L., Ango F. Homer1a-dependent crosstalk between NMDA and metabotropic glutamate receptors in mouse neurons. PLoS ONE 2010, 5(3):e9755.
16. Betancur C., Buxbaum J.D. SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders. Mol. Autism 2013, 4(1):17.
17. Bhakar A.L., Dölen G., Bear M.F. The pathophysiology of fragile X (and what it teaches us about synapses). Annu. Rev. Neurosci. 2012, 35:417-443.
18. Bianchi R., Chuang S.C., Zhao W., Young S.R., Wong R.K. Cellular plasticity for group I mGluR-mediated epileptogenesis. J. Neurosci. 2009, 29:3497-3507.
19. Boer K., Troost D., Timmermans W., Gorter J.A., Spliet W.G., Nellist M., Jansen F., Aronica E. Cellular localization of metabotropic glutamate receptors in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Neuroscience 2008, 156(1):203-215.
20. Bourgeron T. A synaptic trek to autism. Curr. Opin. Neurobiol. 2009, 19(2):231-234.
21. Brakeman P.R., Lanahan A.A., O'Brien R., Roche K., Barnes C.A., Huganir R.L., Worley P.F. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 1997, 386(6622):284-288.
22. Busquets-Garcia A., Gomis-González M., Guegan T., Agustín-Pavón C., Pastor A., Mato S., Pérez-Samartín A., Matute C., de la Torre R., Dierssen M., Maldonado R., Ozaita A. Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat. Med. 2013, 19(5):603-607.
23. Campos A.C., Moreira F.A., Gomes F.V., Del Bel E.A., Guimarães F.S. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos. Trans. R. Soc. Lond. B: Biol. Sci. 2012, 367(1607):3364-3378.
24. Catania M.V., Aronica E., Sortino M.A., Canonico P.L., Nicoletti F. Desensitization of metabotropic glutamate receptors in neuronal cultures. J. Neurochem. 1991, 56(4):1329-1335.
25. Catania M.V., D'Antoni S., Bonaccorso C.M., Aronica E., Bear M.F., Nicoletti F. Group-I metabotropic glutamate receptors: a role in neurodevelopmental disorders?. Mol. Neurobiol. 2007, 35(3):298-307.
26. Chae H.G., Ahn S.J., Hong Y.H., Chang W.S., Kim J., Kim S.J. Transient receptor potential canonical channels regulate the induction of cerebellar long-term depression. J. Neurosci. 2012, 32(37):12909-12914.
27. Chen M., Wan Y., Ade K., Ting J., Feng G., Calakos N. Sapap3 deletion anomalously activates short-term endocannabinoid-mediated synaptic plasticity. J. Neurosci. 2011, 31(26):9563-9573.
28. Chevaleyre V., Takahashi K.A., Castillo P.E. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu. Rev. Neurosci. 2006, 29:37-76.
29. Chévere-Torres I., Kaphzan H., Bhattacharya A., Kang A., Maki J.M., Gambello M.J., Arbiser J.L., Santini E., Klann E. Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the (RG mouse model of tuberous sclerosis complex. Neurobiol. Dis. 2012, 45(3):1101-1110.
30. Chowdhury S., Shepherd J.D., Okuno H., Lyford G., Petralia R.S., Plath N., Kuhl D., Huganir R.L., Worley P.F. Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 2006, 52(3):445-459.
31. Chuang S.C., Zhao W., Bauchwitz R., Yan Q., Bianchi R., Wong R.K. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J. Neurosci. 2005, 25(35):8048-8055.
32. Coutinho V., Kavanagh I., Sugiyama H., Tones M.A., Henley J.M. Characterization of a metabotropic glutamate receptor type 5-green fluorescent protein chimera (mGluR5-GFP): pharmacology, surface expression, and differential effects of Homer-1a and Homer-1c. Mol. Cell Neurosci. 2001, 18:296-306.
33. Craig A.M., Kang Y. Neurexin-neuroligin signaling in synapse development. Curr. Opin. Neurobiol. 2007, 17(1):43-52.
34. Crunelli V., Hughes S.W. The slow (<1Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators. Nat. Neurosci. 2010, 13:9-17.
35. D'Antoni S., Berretta A., Bonaccorso C.M., Bruno V., Aronica E., Nicoletti F., Catania M.V. Metabotropic glutamate receptors in glial cells. Neurochem. Res. 2008, 33(12):2436-2443.
36. Darnell J.C., Van Driesche S.J., Zhang C., Hung K.Y., Mele A., Fraser C.E., Stone E.F., Chen C., Fak J.J., Chi S.W., Licatalosi D.D., Richter J.D., Darnell R.B. FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell 2011, 146(2):247-261.
37. 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.
38. Dolen G., Bear M.F. Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J. Physiol. 2008, 586:1503-1508.
39. Dölen G., Carpenter R.L., Ocain T.D., Bear M.F. Mechanism-based approaches to treating fragile X. Pharmacol. Ther. 2010, 127(1):78-93.
40. Doumazane E., Scholler P., Zwier J.M., Trinquet E., Rondard P., Pin J.P. A new approach to analyze cell surface protein complexes reveals specific heterodimeric metabotropic glutamate receptors. FASEB J. 2011, 25(1):66-77.
41. 2+ exchanger in neuronal cells. Mol. Pharmacol. 1993, 43(6):976-981.
42. Durand C.M., Betancur C., Boeckers T.M., Bockmann J., Chaste P., Fauchereau F., Nygren G., Rastam M., Gillberg I.C., Anckarsäter H., Sponheim E., Goubran-Botros H., Delorme R., Chabane N., Mouren-Simeoni M.C., de Mas P., Bieth E., Rogé B., Héron D., Burglen L., Gillberg C., Leboyer M., Bourgeron T. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 2007, 39(1):25-27.
43. Fatemi S.H., Folsom T.D., Kneeland R.E., Liesch S.B. Metabotropic glutamate receptor 5 upregulation in children with autism is associated with underexpression of both Fragile X mental retardation protein and GABAA receptor beta 3 in adults with autism. Anat. Rec. (Hoboken) 2011, 294(10):1635-1645.
44. Feng W., Tu J., Yang T., Vernon P.S., Allen P.D., Worley P.F., Pessah I.N. Homer regulates gain of ryanodine receptor type 1 channel complex. J. Biol. Chem. 2002, 277(47):44722-44730.
45. Ferreira L.T., Dale L.B., Ribeiro F.M., Babwah A.V., Pampillo M., Ferguson S.S. Calcineurin inhibitor protein (CAIN) attenuates Group I metabotropic glutamate receptor endocytosis and signaling. J. Biol. Chem. 2009, 284(42):28986-28994.
46. Field J.R., Walker A.G., Conn P.J. Targeting glutamate synapses in schizophrenia. Trends Mol. Med. 2011, 17(12):689-698.
47. Fujii S., Yamazaki Y., Kuroda Y., Mikoshiba K. Involvement of inositol-1,4,5-trisphosphate receptors in the bidirectional synaptic plasticity induced in hippocampal CA1 neurons by 1-10Hz low-frequency stimulation. Neuroscience 2010, 168(2):346-358.
48. Gereau R.W., Conn P.J. Multiple presynaptic metabotropic glutamate receptors modulate excitatory and inhibitory synaptic transmission in hippocampal area CA1. J. Neurosci. 1995, 15(10):6879-6889.
49. Gereau R.W., Heinemann S.F. Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5. Neuron 1998, 20(1):143-151.
50. Gilby K.L., O'Brien T.J. Epilepsy, autism, and neurodevelopment: kindling a shared vulnerability?. Epilepsy Behav. 2013, 26:370-374.
51. Giuffrida R., Musumeci S., D'Antoni S., Bonaccorso C.M., Giuffrida-Stella A.M., Oostra B.A., Catania M.V. A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome. J. Neurosci. 2005, 25(39):8908-8916.
52. Gladding C.M., Fitzjohn S.M., Molnár E. Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms. Pharmacol. Rev. 2009, 61(4):395-412.
53. Gomeza J., Joly C., Kuhn R., Knöpfel T., Bockaert J., Pin J.P. The second intracellular loop of metabotropic glutamate receptor 1 cooperates with the other intracellular domains to control coupling to G-proteins. J. Biol. Chem. 1996, 271(4):2199-2205.
54. 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.
55. Goorden S.M., van Woerden G.M., van der Weerd L., Cheadle J.P., Elgersma Y. Cognitive deficits in Tsc1+/- mice in the absence of cerebral lesions and seizures. Ann. Neurol. 2007, 62(6):648-655.
56. Goudet C., Kniazeff J., Hlavackova V., Malhaire F., Maurel D., Acher F., Blahos J., Prézeau L., Pin J.P. Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J. Biol. Chem. 2005, 280(26):24380-24385.
57. Gray N.W., Fourgeaud L., Huang B., Chen J., Cao H., Oswald B.J., Hémar A., McNiven M.A. Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer. Curr. Biol. 2003, 13(6):510-515.
58. Gross C., Nakamoto M., Yao X., Chan C.B., Yim S.Y., Ye K., Warren S.T., Bassell G.J. Excess phosphoinositide 3-kinase subunit synthesis and activity as a novel therapeutic target in fragile X syndrome. J. Neurosci. 2010, 30(32):10624-10638.
59. Haider B., McCormick D.A. Rapid neocortical dynamics: cellular and network mechanisms. Neuron 2009, 62(2):171-189.
60. Hayashi M.K., Ames H.M., Hayashi Y. Tetrameric hub structure of postsynaptic scaffolding protein homer. J. Neurosci. 2006, 26(33):8492-8501.
61. Hayashi M.K., Tang C., Verpelli C., Narayanan R., Stearns M.H., Xu R.M., Li H., Sala C., Hayashi Y. The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell 2009, 137(1):159-171.
62. Hays S.A., Huber K.M., Gibson J.R. Altered neocortical rhythmic activity states in Fmr1 KO mice are due to enhanced mGluR5 signaling and involve changes in excitatory circuitry. J. Neurosci. 2011, 31(40):14223-14234.
63. Hermans E., Challiss R.A.J. Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors. Biochem. J. 2001, 359:465-484.
64. Holbro N., Grunditz A., Oertner T.G. Differential distribution of endoplasmic reticulum controls metabotropic signaling and plasticity at hippocampal synapses. Proc. Natl. Acad. Sci. U.S.A. 2009, 106(35):15055-15060.
65. Holler T., Cappel E., Klein J., Löffelholz K. Glutamate activates phospholipase D in hippocampal slices of newborn and adult rats. J. Neurochem. 1993, 61(4):1569-1572.
66. Hou L., Klann E. Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J. Neurosci. 2004, 24(28):6352-6361.
67. 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, 51:441-454.
68. Hu J.H., Yang L., Kammermeier P.J., Moore C.G., Brakeman P.R., Tu J., Yu S., Petralia R.S., Li Z., Zhang P.W., Park J.M., Dong X., Xiao B., Worley P.F. Preso1 dynamically regulates group I metabotropic glutamate receptors. Nat. Neurosci. 2012, 15(6):836-844.
69. Huang Y., Lu W., Ali D.W., Pelkey K.A., Pitcher G.M., Lu Y.M., Aoto H., Roder J.C., Sasaki T., Salter M.W., MacDonald J.F. CAKbeta/Pyk2 kinase is a signaling link for induction of long-term potentiation in CA1 hippocampus. Neuron 2001, 29(2):485-496.
70. Huang J., Manning B.D. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem. J. 2008, 412(2):179-190.
71. Huber K.M., Kayser M.S., Bear M.F. Role for rapid dendritic protein synthesis in hippocampal mGluR-dependent long-term depression. Science 2000, 288:1254-1257.
72. 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. U.S.A. 2002, 99(11):7746-7750.
73. Hung A.Y., Futai K., Sala C., Valtschanoff J.G., Ryu J., Woodworth M.A., Kidd F.L., Sung C.C., Miyakawa T., Bear M.F., Weinberg R.J., Sheng M. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J. Neurosci. 2008, 28:1697-1708.
74. Iacovelli L., Nicoletti F., De Blasi A. Molecular mechanisms that desensitize metabotropic glutamate receptor signaling: an overview. Neuropharmacology 2013, 66:24-30.
75. Irwin S.A., Patel B., Idupulapati M., Harris J.B., Crisostomo R., Kooy F., Willems P.J., Cras P., Kozlowski P.B., Weiler I.J., Greenough W.T. Abnormal dendritic spine characteristics in the temporal cortex of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet. 2001, 98:161-167.
76. 2+/calmodulin with the cytoplasmic tail of group 1 metabotropic glutamate receptors. Genes Cells 1999, 4(7):381-390.
77. Jia Z., Lu Y., Henderson J., Taverna F., Romano C., Abramow-Newerly W., Wojtowicz J.M., Roder J. Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn. Mem. 1998, 5:331-343.
78. Jiang Y.H., Ehlers M.D. Modeling autism by SHANK gene mutations in mice. Neuron 2013, 78:8-27.
79. Ji D., Wilson M.A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat. Neurosci. 2007, 10:100-107.
80. Jong Y.J., Kumar V., O'Malley K.L. Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts. J. Biol. Chem. 2009, 284:35827-35838.
81. Jung K.M., Mangieri R., Stapleton C., Kim J., Fegley D., Wallace M., Mackie K., Piomelli D. Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors. Mol. Pharmacol. 2005, 68(5):1196-1202.
82. Jung K.M., Astarita G., Zhu C., Wallace M., Mackie K., Piomelli D. A key role for diacylglycerol lipase-alpha in metabotropic glutamate receptor-dependent endocannabinoid mobilization. Mol. Pharmacol. 2007, 72(3):612-621.
83. Jung K.M., Sepers M., Henstridge C.M., Lassalle O., Neuhofer D., Martin H., Ginger M., Frick A., DiPatrizio 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. Commun. 2012, 3:1080.
84. Kammermeier P.J., Xiao B., Tu J.C., Worley P.F., Ikeda S.R. Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channel. J. Neurosci. 2000, 20(19):7238-7245.
85. Kammermeier P.J., Worley P.F. Homer 1a uncouples metabotropic glutamate receptor 5 from postsynaptic effectors. Proc. Natl. Acad. Sci. U.S.A. 2007, 104(14):6055-6060.
86. Kato A., Ozawa F., Saitoh Y., Fukazawa Y., Sugiyama H., Inokuchi K. Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. J. Biol. Chem. 1998, 273(37):23969-23975.
87. Katona I., Sperlágh B., Sík A., Käfalvi A., Vizi E.S., Mackie K., Freund T.F. Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons. J. Neurosci. 1999, 19(11):4544-4558.
88. Kawabata S., Tsutsumi R., Kohara A., Yamaguchi T., Nakanishi S., Okada M. Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors. Nature 1996, 383(6595):89-92.
89. Kelleher R.J., Bear M.F. The autistic neuron: troubled translation?. Cell 2008, 135:401-406.
90. Kelleher R.J., Geigenmüller U., Hovhannisyan H., Trautman E., Pinard R., Rathmell B., Carpenter R., Margulies D. High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism. PLoS ONE 2012, 7(4):e35003.
91. Kim E., Naisbitt S., Hsueh Y.P., Rao A., Rothschild A., Craig A.M., Sheng M. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules. J. Cell Biol. 1997, 136(3):669-678.
92. Kim J.Y., Zeng W., Kiselyov K., Yuan J.P., Dehoff M.H., Mikoshiba K., Worley P.F., Muallem S. Homer 1 mediates store- and inositol 1,4,5-trisphosphate receptor-dependent translocation and retrieval of TRPC3 to the plasma membrane. J. Biol. Chem. 2006, 281(43):32540-32549.
93. Kitano J., Kimura K., Yamazaki Y., Soda T., Shigemoto R., Nakajima Y., Nakanishi S. Tamalin, a PDZ domain-containing protein, links a protein complex formation of group 1 metabotropic glutamate receptors and the guanine nucleotide exchange factor cytohesins. J. Neurosci. 2002, 22:1280-1289.
94. Kniazeff J., Bessis A.S., Maurel D., Ansnay H., Prezeau L., Pin J-P. Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat. Struct. Mol. Biol. 2004, 11(8):706-713.
95. Ko S.J., Isozaki K., Kim I., Lee J.H., Cho H.J., Sohn S.Y., Oh S.R., Park S., Kim D.G., Kim C.H., Roche K.W. PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A. J. Neurosci. 2012, 32(46):16391-16401.
96. Koekkoek S.K., Yamaguchi K., Milojkovic B.A., Dortland B.R., Ruigrok T.J., Maex R., De Graaf W., Smit A.E., VanderWerf F., Bakker C.E., Willemsen R., Ikeda T., Kakizawa S., Onodera K., Nelson D.L., Mientjes E., Joosten M., De Schutter E., Oostra B.A., Ito M., De Zeeuw C.I. Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron 2005, 47(3):339-352.
97. Kotecha S.A., Jackson M.F., Al-Mahrouki A., Roder J.C., Orser B.A., MacDonald J.F. Co-stimulation of mGluR5 and N-methyl-d-aspartate receptors is required for potentiation of excitatory synaptic transmission in hippocampal neurons. J. Biol. Chem. 2003, 278(30):27742-27749.
98. Krueger D.D., Bear M.F. Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu. Rev. Med. 2011, 62:411-429.
99. Kumar V., Jong Y.J., O'Malley K.L. Activated nuclear metabotropic glutamate receptor mGlu5 couples to nuclear Gq/11 proteins to generate inositol 1,4,5-trisphosphate-mediated nuclear Ca2+ release. J. Biol. Chem. 2008, 283:14072-14083.
100. Kwon C.H., Luikart B.W., Powell C.M., Zhou J., Matheny S.A., Zhang W., Li Y., Baker S.J., Parada L.F. Pten regulates neuronal arborization and social interaction in mice. Neuron 2006, 50(3):377-388.
101. Lafourcade M., Elezgarai I., Mato S., Bakiri Y., Grandes P., Manzoni O.J. Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS ONE 2007, 2(8):e709.
102. Lee J.H., Lee J., Choi K.Y., Hepp R., Lee J.Y., Lim M.K., Chatani-Hinze M., Roche P.A., Kim D.G., Ahn Y.S., Kim C.H., Roche K.W. Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5. Proc. Natl. Acad. Sci. U.S.A. 2008, 105(34):12575-12580.
103. Lohith T.G., Osterweil E.K., Fujita M., Jenko K.J., Bear M.F., Innis R.B. Is metabotropic glutamate receptor 5 upregulated in prefrontal cortex in fragile X syndrome?. Mol. Autism 2013, 4(1):15.
104. Lu Y.M., Jia Z., Janus C., Henderson J.T., Gerlai R., Wojtowicz J.M., Roder J.C. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J. Neurosci. 1997, 17:5196-5205.
105. Lu W.Y., Xiong Z.G., Lei S., Orser B.A., Dudek E., Browning M.D., MacDonald J.F. G-protein-coupled receptors act via protein kinase C and Src to regulate NMDA receptors. Nat. Neurosci. 1999, 2(4):331-338.
106. Lujan R., Roberts J.D., Shigemoto R., Ohishi H., Somogyi P. Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. J. Chem. Neuroanat. 1997, 13:219-241.
107. Lüscher 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. (review).
108. Maccarrone M., Rossi S., Bari M., De Chiara V., Fezza F., Musella A., Gasperi V., Prosperetti C., Bernardi G., Finazzi-Agrò A., Cravatt B.F., Centonze D. Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. Nat. Neurosci. 2008, 11(2):152-159.
109. Maccarrone M., Rossi S., Bari M., De Chiara V., Rapino C., Musella A., Bernardi G., Bagni C., Centonze D. Abnormal mGlu 5 receptor/endocannabinoid coupling in mice lacking FMRP and BC1 RNA. Neuropsychopharmacology 2010, 35(7):1500-1509.
110. Mannaioni G., Marino M.J., Valenti O., Traynelis S.F., Conn P.J. Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J. Neurosci. 2001, 21(16):5925-5934.
111. Mao L., Yang L., Tang Q., Samdani S., Zhang G., Wang J.W. The scaffold protein homer1b/c links metabotropic glutamate receptor 5 to extracellular signal-regulated protein kinase cascades in neurons. J. Neurosci. 2005, 25(10):2741-2752.
112. Marshall L., Helgadottir H., Molle M., Born J. Boosting slow oscillations during sleep potentiates memory. Nature 2006, 444:610-613.
113. Marshall L., Born J. The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn. Sci. 2007, 11:442-450.
114. McBride K.L., Varga E.A., Pastore M.T., Prior T.W., Manickam K., Atkin J.F., Herman G.E. Confirmation study of PTEN mutations among individuals with autism or developmental delays/mental retardation and macrocephaly. Autism Res. 2010, (3):137-141.
115. McFarlane H.G., Kusek G.K., Yang M., Phoenix J.L., Bolivar V.J., Crawley J.N. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 2008, 7:152-163.
116. Moriyoshi K., Iijima K., Fujii H., Ito H., Cho Y., Nakanishi S. Seven in absentia homolog 1A mediates ubiquitination and degradation of group 1 metabotropic glutamate receptors. Proc. Natl. Acad. Sci. U.S.A. 2004, 101(23):8614-8619.
117. Moult P.R., Gladding C.M., Sanderson T.M., Fitzjohn S.M., Bashir Z.I., Molnar E., Collingridge G.L. Tyrosine phosphatases regulate AMPA receptor trafficking during metabotropic glutamate receptor-mediated long-term depression. J. Neurosci. 2006, 26(9):2544-2554.
118. Moutin E., Raynaud F., Roger J., Pellegrino E., Homburger V., Bertaso F., Ollendorff V., Bockaert J., Fagni L., Perroy J. Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability. J. Cell Biol. 2012, 198(2):251-263.
119. Musumeci S.A., Bosco P., Calabrese G., Bakker C., De Sarro G.B., Elia M., Ferri R., Oostra B.A. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 2000, 41(1):19-23.
120. Musumeci S.A., Calabrese G., Bonaccorso C.M., D'Antoni S., Brouwer J.R., Bakker C.E., Elia M., Ferri R., Nelson D.L., Oostra B.A., Catania M.V. Audiogenic seizure susceptibility is reduced in fragile X knockout mice after introduction of FMR1 transgenes. Exp. Neurol. 2007, 203(1):233-240.
121. Nadif Kasri N., Nakano-Kobayashi A., Van Aelst L. Rapid synthesis of the X-linked mental retardation protein OPHN1 mediates mGluR-dependent LTD through interaction with the endocytic machinery. Neuron 2011, 72(2):300-315.
122. Naie K., Manahan-Vaughan D. Regulation by metabotropic glutamate receptor 5 of LTP in the dentate gyrus of freely moving rats: relevance for learning and memory formation. Cereb. Cortex 2004, 14(2):189-198.
123. 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.
124. 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, 32:2582-2587.
125. 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.
126. Niere F., Wilkerson J.R., Huber K.M. Evidence for a fragile X mental retardation protein-mediated translational switch in metabotropic glutamate receptor-triggered Arc translation and long-term depression. J. Neurosci. 2012, 32:5924-5936.
127. Nimchinsky E.A., Oberlander A.M., Svoboda K. Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 2001, 21(14):5139-5146.
128. Niswender C.M., Conn P.J. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Ann. Rev. Pharmacol. Toxicol. 2010, 50:295-322.
129. 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, 95:3291-3295.
130. Nusser Z., Mulvihill E., Streit P., Somogyi P. Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization. Neuroscience 1994, 61(3):421-427.
131. 2+ changes in heterologous cell types and neurons. J. Biol. Chem. 2003, 278(30):28210-28219.
132. Orlando L.R., Ayala R., Kett L.R., Curley A.A., Duffner J., Bragg D.C., Tsai L.H., Dunah A.W., Young A.B. Phosphorylation of the homer-binding domain of group I metabotropic glutamate receptors by cyclin-dependent kinase 5. J. Neurochem. 2009, 110(2):557-569.
133. Osterweil E.K., Krueger D.D., Reinhold K., Bear M.F. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome. J. Neurosci. 2010, 30:15616-15627.
134. Osterweil E.K., Chuang S.C., Chubykin A.A., Sidorov M., Bianchi R., Wong R.K., Bear M.F. Lovastatin corrects excess protein synthesis and prevents epileptogenesis in a mouse model of fragile X syndrome. Neuron 2013, 77:243-250.
135. 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, 59:70-83.
136. Peavy R.D., Conn P.J. Phosphorylation of mitogen-activated protein kinase in cultured rat cortical glia by stimulation of metabotropic glutamate receptors. J. Neurochem. 1998, 71(2):603-612.
137. Peça J., Feliciano C., Ting J.T., Wang W., Wells M.F., Venkatraman T.N., Lascola C.D., Fu Z., Feng G. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011, 472:437-442.
138. Pfeiffer B.E., Huber K.M. The state of synapses in fragile X syndrome. Neuroscientist 2009, 15:549-567.
139. Phelan M.C. Deletion 22q13.3 syndrome. Orphanet J. Rare Dis. 2008, 3:14.
140. Pin J.P., Gomeza J., Joly C., Bockaert J. The metabotropic glutamate receptors: their second intracellular loop plays a critical role in the G-protein coupling specificity. Biochem. Soc. Trans. 1995, 23(1):91-96.
141. Pin J.P., Kniazeff J., Liu J., Binet V., Goudet C., Rondard P., Prezeau L. Allosteric functioning of dimeric class C G-protein-coupled receptors. FEBS J. 2005, 272:2947-2955.
142. Pisani A., Gubellini P., Bonsi P., Conquet F., Picconi B., Centonze D., Bernardi G., Calabresi P. Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-d-aspartate responses in medium spiny striatal neurons. Neuroscience 2001, 106(3):579-587.
143. Portera-Cailliau C. Which comes first in fragile X syndrome, dendritic spine dysgenesis or defects in circuit plasticity?. Neuroscientist 2012, 18:28-44.
144. Robbe D., Kopf M., Remaury A., Bockaert J., Manzoni O.J. Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens. Proc. Natl. Acad. Sci. U.S.A. 2002, 99(12):8384-8388.
145. Roloff A.M., Anderson G.R., Martemyanov K.A., Thayer S.A. Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity. J. Neurosci. 2010, 30(8):3072-3081.
146. Romano C., van den Pol A.N., O'Malley K.L. Enhanced early developmental expression of the metabotropic glutamate receptor mGluR5 in rat brain: protein, mRNA splice variants, and regional distribution. J. Comp. Neurol. 1996, 367(3):403-412.
147. Ronesi J.A., Huber K.M. Metabotropic glutamate receptors and fragile x mental retardation protein: partners in translational regulation at the synapse. Sci. Signal. 2008, 1(5):pe6.
148. Ronesi J.A., Collins K.A., Hays S.A., Tsai N.P., Guo W., Birnbaum S.G., Hu J.H., Worley P.F., Gibson J.R., Huber K.M. Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome. Nat. Neurosci. 2012, 15(3):431-434.
149. Rong R., Ahn J.Y., Huang H., Nagata E., Kalman D., Kapp J.A., Tu J., Worley P.F., Snyder S.H., Ye K. PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis. Nat. Neurosci. 2003, 6(11):1153-1161.
150. Sanchez-Vives M.V., Mattia M., Compte A., Perez-Zabalza M., Winograd M., Descalzo V.F., Reig R. Inhibitory modulation of cortical up states. J. Neurophysiol. 2010, 104:1314-1324.
151. Sato D., Lionel A.C., Leblond C.S., Prasad A., Pinto D., Walker S., O'Connor I., Russell 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., Stavropoulos 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.
152. Sergé A., Fourgeaud L., Hémar A., Choquet D. Receptor activation and Homer differentially control the lateral mobility of metabotropic glutamate receptor 5 in the neuronal membrane. J. Neurosci. 2002, 22(10):3910-3920.
153. Sharma A., Hoeffer C.A., Takayasu Y., Miyawaki T., McBride S.M., Klann E., Zukin R.S. Dysregulation of mTOR signaling in fragile X syndrome. J. Neurosci. 2010, 30(2):694-702.
154. Shigemoto R., Kinoshita A., Wada E., Nomura S., Ohishi H., Takada M., Flor P.J., Neki A., Abe T., Nakanishi S., Mizuno N. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J. Neurosci. 1997, 17(19):7503-7522.
155. Shiraishi Y., Mizutani A., Bito H., Fujisawa K., Narumiya S., Mikoshiba K., Furuichi T. Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. J. Neurosci. 1999, 19(19):8389-8400.
156. Shiraishi-Yamaguchi Y., Furuichi T. The Homer family proteins. Genome Biol. 2007, 8(2):206.
157. Sylantyev S., Savtchenko L.P., Ermolyuk Y., Michaluk P., Rusakov D.A. Spike-driven glutamate electrodiffusion triggers synaptic potentiation via a homer-dependent mGluR-NMDAR link. Neuron 2013, 77(3):528-541.
158. 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.
159. 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.
160. Takeuchi M., Hata Y., Hirao K., Toyoda A., Irie M., Takai Y. SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J. Biol. Chem. 1997, 272(18):11943-11951.
161. Takeuchi K., Gertner M.J., Zhou J., Parada L.F., Bennett M.V., Zukin R.S. Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism. Proc. Natl. Acad. Sci. U.S.A. 2013, 110(12):4738-4743.
162. Taufiq A.M., Fujii S., Yamazaki Y., Sasaki H., Kaneko K., Li J., Kato H., Mikoshiba K. Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal CA1 neurons. Learn. Mem. 2005, 12(6):594-600.
163. Thomas L.S., Jane D.E., Harris J.R., Croucher M.J. Metabotropic glutamate autoreceptors of the mGlu(5) subtype positively modulate neuronal glutamate release in the rat forebrain in vitro. Neuropharmacology 2000, 39(9):1554-1566.
164. Tu J.C., Xiao B., Yuan J.P., Lanahan A.A., Leoffert K., Li M., Linden D.J., Worley P.F. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 1998, 21:717-726.
165. Tu J.C., Xiao B., Naisbitt S., Yuan J.P., Petralia R.S., Brakeman P., Doan A., Aakalu V.K., Lanahan A.A., Sheng M., Worley P.F. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 1999, 23(3):583-592.
166. van Hooft J.A., Giuffrida R., Blatow M., Monyer H. Differential expression of group I metabotropic glutamate receptors in functionally distinct hippocampal interneurons. J. Neurosci. 2000, 20(10):3544-3551.
167. Varma N., Carlson G.C., Ledent C., Alger B.E. Metabotropic glutamate receptors drive the endocannabinoid system in hippocampus. J. Neurosci. 2001, 21(24):RC188.
168. Verpelli C., Dvoretskova E., Vicidomini C., Rossi F., Chiappalone M., Schoen M., Di Stefano B., Mantegazza R., Broccoli V., Böckers T.M., Dityatev A., Sala C. Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J. Biol. Chem. 2011, 286(40):34839-34850.
169. Vidnyanszky Z., Gorcs T.J., Negyessy L., Borostyankio Z., Knopfel T., Hamori J. Immunocytochemical visualization of the mGluR1a metabotropic glutamate receptor at synapses of corticothalamic terminals originating from area 17 of the rat. Eur. J. Neurosci. 1996, 8(6):1061-1071.
170. Wan Y., Feng G., Calakos N. Sapap3 deletion causes mGluR5-dependent silencing of AMPAR synapses. J. Neurosci. 2011, 31(46):16685-16691.
171. Wang H., Westin L., Nong Y., Birnbaum S., Bendor J., Brismar H., Nestler E., Aperia A., Flajolet M., Greengard P. Norbin is an endogenous regulator of metabotropic glutamate receptor 5 signaling. Science 2009, 326(5959):1554-1557.
172. Wang X., McCoy P., Rodriguiz R.M., Pan Y., Je H.S., Roberts A., Kim C., 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, 20:3093-3108.
173. Wang X., Bey A.L., Chung L., Krystal A.D., Jiang Y.H. Therapeutic approaches for shankopathies. Dev. Neurobiol. 2014, 74(2):123-135.
174. Waung M.W., Pfeiffer B.E., Nosyreva E.D., Ronesi J.A., Huber K.M. Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron 2008, 59(1):84-97.
175. Waung M.W., Huber K.M. Protein translation in synaptic plasticity: mGluR-LTD, Fragile X. Curr. Opin. Neurobiol. 2009, 19(3):319-326.
176. Weiler I.J., Irwin S.A., Klintsova A.Y., Spencer C.M., Brazelton A.D., Miyashiro K., Comery T.A., Patel B., Eberwine J., Greenough W.T. Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:5395-5400.
177. Welch J.M., Lu J., Rodriguiz R.M., Trotta N.C., Peca J., Ding J.D., Feliciano C., Chen M., Adams J.P., Luo J., Dudek S.M., Weinberg R.J., Calakos N., Wetsel W.C., Feng G. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 2007, 448(7156):894-900.
178. Wilson R.I., Nicoll R.A. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature 2001, 410(6828):588-592.
179. Wiznitzer M. Autism and tuberous sclerosis. J. Child Neurol. 2004, 19(9):675-679.
180. 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.
181. Yan Q.J., Rammal M., Tranfaglia M., Bauchwitz R.P. Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 2005, 49:1053-1066.
182. Yoshida T., Fukaya M., Uchigashima M., Miura E., Kamiya H., Kano M., Watanabe M. Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. J. Neurosci. 2006, 26:4740-4751.
183. Yuan J.P., Kiselyov K., Shin D.M., Chen J., Shcheynikov N., Kang S.H., Dehoff M.H., Schwarz M.K., Seeburg P.H., Muallem S., Worley P.F. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 2003, 114(6):777-789.
184. Xiao B., Tu J.C., Petralia R.S., Yuan J.P., Doan A., Breder C.D., Ruggiero A., Lanahan A.A., Wenthold R.J., Worley P.F. Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins. Neuron 1998, 21:707-716.
185. 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.
186. Zhang L., Alger B.E. Enhanced endocannabinoid signaling elevates neuronal excitability in fragile X syndrome. J. Neurosci. 2010, 30(16):5724-5729.
187. Zhou J., Parada L.F. PTEN signaling in autism spectrum disorders. Curr. Opin. Neurobiol. 2012, 22(5):873-879.