Dendritic spine dysgenesis in Rett syndrome

Frontiers in Neuroanatomy

Volumn 8, Issue , 2014, Pages 1-8

  Xu, Xin ^a   Miller, Eric C ^a   Pozzo Miller, Lucas ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

Autism spectrum disorder; BDNF; Excitatory synapse; Hippocampus; MeCP2; Organotypic slice cultures; Spine density; TrkB

Indexed keywords

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR AGONIST; GLUTAMIC ACID DERIVATIVE; GLYCYL L METHYLPROLYL L GLUTAMIC ACID; LM22A 4; METHYL CPG BINDING PROTEIN 2; RECOMBINANT SOMATOMEDIN C; SOMATOMEDIN C; UNCLASSIFIED DRUG;

CELL STRUCTURE; DENDRITIC SPINE; HUMAN; NERVE CELL DIFFERENTIATION; NERVE CELL PLASTICITY; NONHUMAN; RETT SYNDROME; REVIEW; SIGNAL TRANSDUCTION; SPINE MALFORMATION;

EID: 84907188787     PISSN: None     EISSN: 16625129     Source Type: Journal    
DOI: 10.3389/fnana.2014.00097     Document Type: Review

References (120)

1. Alonso, M., Medina, J. H., and Pozzo-Miller, L. (2004). ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons. Learn. Mem. 11, 172-178. doi: 10.1101/lm.67804
2. Amaral, M. D., and Pozzo-Miller, L. (2007). TRPC3 channels are necessary for brain-derived neurotrophic factor to activate a nonselective cationic current and to induce dendritic spine formation. J. Neurosci. 27, 5179-5189. doi: 10.1523/JNEUROSCI.5499-06.2007
3. Amir, R. E., Van Den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., and Zoghbi, H. Y. (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23, 185-188. doi: 10.1038/13810
4. Armstrong, D., Dunn, J. K., Antalffy, B., and Trivedi, R. (1995). Selective dendritic alterations in the cortex of Rett syndrome. J. Neuropathol. Exp. Neurol. 54, 195-201. doi: 10.1097/00005072-199503000-00006
5. Baj, G., Patrizio, A., Montalbano, A., Sciancalepore, M., and Tongiorgi, E. (2014). Developmental and maintenance defects in Rett syndrome neurons identified by a new mouse staging system in vitro. Front. Cell. Neurosci. 8:18. doi: 10.3389/fncel.2014.00018
6. Belichenko, P. V., Oldfors, A., Hagberg, B., and Dahlstrom, A. (1994). Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport 5, 1509-1513. doi: 10.1097/00001756-199407000-00025
7. Belichenko, P. V., Wright, E. E., Belichenko, N. P., Masliah, E., Li, H. H., Mobley, W. C.,et al. (2009). Widespread changes in dendritic and axonal morphology in Mecp2-mutant mouse models of Rett syndrome: evidence for disruption of neuronal networks. J. Comp. Neurol. 514, 240-258. doi: 10.1002/cne.22009
8. Bhatt, D. H., Zhang, S., and Gan, W. B. (2009). Dendritic spine dynamics. Annu. Rev. Physiol. 71, 261-282. doi: 10.1146/annurev.physiol.010908.163140
9. Blackman, M. P., Djukic, B., Nelson, S. B., and Turrigiano, G. G. (2012). A critical and cell-autonomous role for MeCP2 in synaptic scaling up. J. Neurosci. 32, 13529-13536. doi: 10.1523/JNEUROSCI.3077-12.2012
10. 2+ signaling in dendritic spines. Curr. Opin. Neurobiol. 17, 345-351. doi: 10.1016/j.conb.2007.04.003
11. Bourgeron, T. (2009). A synaptic trek to autism. Curr. Opin. Neurobiol. 19, 231-234. doi: 10.1016/j.conb.2009.06.003
12. Calfa, G., Hablitz, J. J., and Pozzo-Miller, L. (2011a). Network hyperexcitability in hippocampal slices from Mecp2 mutant mice revealed by voltage-sensitive dye imaging. J. Neurophysiol. 105, 1768-1784. doi: 10.1152/jn.00800.2010
13. Calfa, G., Percy, A. K., and Pozzo-Miller, L. (2011b). Experimental models of Rett syndrome based on Mecp2 dysfunction. Exp. Biol. Med. (Maywood) 236, 3-19. doi: 10.1258/ebm.2010.010261
14. Carlsson-Skwirut, C., Lake, M., Hartmanis, M., Hall, K., and Sara, V. R. (1989). A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1). Biochim. Biophys. Acta 1011, 192-197. doi: 10.1016/0167-4889(89)90209-7
15. Carvalho, A. L., Caldeira, M. V., Santos, S. D., and Duarte, C. B. (2008). Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br. J. Pharmacol. 153(Suppl. 1), S310-S324. doi: 10.1038/sj.bjp.0707509
16. Castro, J., Garcia, R. I., Kwok, S., Banerjee, A., Petravicz, J., Woodson, J.,et al. (2014). Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome. Proc. Natl. Acad. Sci. U.S.A. 111, 9941-9946. doi: 10.1073/pnas.1311685111
17. Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T., Qin, J.,et al. (2008). MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 320, 1224-1229. doi: 10.1126/science.1153252
18. Chahrour, M., and Zoghbi, H. Y. (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron 56, 422-437. doi: 10.1016/j.neuron.2007.10.001
19. Chang, Q., Khare, G., Dani, V., Nelson, S., and Jaenisch, R. (2006). The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49, 341-348. doi: 10.1016/j.neuron.2005.12.027
20. Chao, H. T., Zoghbi, H. Y., and Rosenmund, C. (2007). MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron 56, 58-65. doi: 10.1016/j.neuron.2007.08.018
21. Chapleau, C. A., Boggio, E. M., Calfa, G., Percy, A. K., Giustetto, M., and Pozzo-Miller, L. (2012). Hippocampal CA1 pyramidal neurons of Mecp2 mutant mice show a dendritic spine phenotype only in the presymptomatic stage.Neural Plast. 2012, 976164. doi: 10.1155/2012/976164
22. Chapleau, C. A., Calfa, G. D., Lane, M. C., Albertson, A. J., Larimore, J. L., Kudo, S.,et al. (2009a). Dendritic spine pathologies in hippocampal pyramidal neurons from Rett syndrome brain and after expression of Rett-associated MECP2 mutations. Neurobiol. Dis. 35, 219-233. doi: 10.1016/j.nbd.2009.05.001
23. Chapleau, C. A., Larimore, J. L., Theibert, A., and Pozzo-Miller, L. (2009b). Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. J. Neurodev. Disord 1, 185-196. doi: 10.1007/s11689-009-9027-6
24. Chapleau, C. A., Carlo, M. E., Larimore, J. L., and Pozzo-Miller, L. (2008). The actions of BDNF on dendritic spine density and morphology in organotypic slice cultures depend on the presence of serum in culture media. J. Neurosci. Methods 169, 182-190. doi: 10.1016/j.jneumeth.2007.12.006
25. Chen, R. Z., Akbarian, S., Tudor, M., and Jaenisch, R. (2001). Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat. Genet. 27, 327-331. doi: 10.1038/85906
26. Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C.,et al. (2003). Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 302, 885-889. doi: 10.1126/science.1086446
27. Chen, Z. Y., Jing, D., Bath, K. G., Ieraci, A., Khan, T., Siao, C. J.,et al. (2006). Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 314, 140-143. doi: 10.1126/science.1129663
28. Chen, Z. Y., Patel, P. D., Sant, G., Meng, C. X., Teng, K. K., Hempstead, B. L.,et al. (2004). Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J. Neurosci. 24, 4401-4411. doi: 10.1523/JNEUROSCI.0348-04.2004
29. Cheng, T. L., Wang, Z., Liao, Q., Zhu, Y., Zhou, W. H., Xu, W.,et al. (2014). MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex. Dev. Cell 28, 547-560. doi: 10.1016/j.devcel.2014.01.032
30. Cohen, D. R., Matarazzo, V., Palmer, A. M., Tu, Y., Jeon, O. H., Pevsner, J.,et al. (2003). Expression of MeCP2 in olfactory receptor neurons is developmentally regulated and occurs before synaptogenesis. Mol. Cell. Neurosci.22, 417-429. doi: 10.1016/S1044-7431(03)00026-5
31. Cohen-Cory, S., Kidane, A. H., Shirkey, N. J., and Marshak, S. (2010). Brain-derived neurotrophic factor and the development of structural neuronal connectivity. Dev. Neurobiol. 70, 271-288. doi: 10.1002/dneu.20774
32. Corvin, A. P., Molinos, I., Little, G., Donohoe, G., Gill, M., Morris, D. W.,et al. (2012). Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms. Neurosci. Lett. 520, 51-56. doi: 10.1016/j.neulet.2012.05.029
33. D’Ercole, A. J. (1996). Insulin-like growth factors and their receptors in growth. Endocrinol. Metab. Clin. North. Am. 25, 573-590. doi: 10.1016/S0889-8529(05)70341-8
34. Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A.,et al. (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257-269. doi: 10.1016/S0092-8674(03)00035-7
35. Fiala, J. C., Feinberg, M., Popov, V., and Harris, K. M. (1998). Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J. Neurosci. 18, 8900-8911.
36. Fiala, J. C., Spacek, J., and Harris, K. M. (2002). Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res. Brain Res. Rev. 39, 29-54. doi: 10.1016/S0165-0173(02)00158-3
37. Figurov, A., Pozzo-Miller, L. D., Olafsson, P., Wang, T., and Lu, B. (1996). Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381, 706-709. doi: 10.1038/381706a0
38. Fukuda, T., Itoh, M., Ichikawa, T., Washiyama, K., and Goto, Y. (2005). Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J. Neuropathol. Exp. Neurol. 64, 537-544.
39. Garey, L. (2010). When cortical development goes wrong: schizophrenia as a neurodevelopmental disease of microcircuits. J. Anat. 217, 324-333. doi: 10.1111/j.1469-7580.2010.01231.x
40. Grutzendler, J., Kasthuri, N., and Gan, W. B. (2002). Long-term dendritic spine stability in the adult cortex. Nature420, 812-816. doi: 10.1038/nature01276
41. Guy, J., Hendrich, B., Holmes, M., Martin, J. E., and Bird, A. (2001). A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat. Genet. 27, 322-326. doi: 10.1038/85899
42. Harris, K. M., and Stevens, J. K. (1989). Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics. J. Neurosci. 9, 2982-2997.
43. Holtmaat, A. J., Trachtenberg, J. T., Wilbrecht, L., Shepherd, G. M., Zhang, X., Knott, G. W.,et al. (2005). Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45, 279-291. doi: 10.1016/j.neuron.2005.01.003
44. Hoogenraad, C. C., and Akhmanova, A. (2010). Dendritic spine plasticity: new regulatory roles of dynamic microtubules. Neuroscientist 16, 650-661. doi: 10.1177/1073858410386357
45. Huang, E. J., and Reichardt, L. F. (2003). Trk receptors: roles in neuronal signal transduction. Annu. Rev. Biochem.72, 609-642. doi: 10.1146/annurev.biochem.72.121801.161629
46. Huttenlocher, P. R. (1970). Dendritic development and mental defect. Neurology 20, 381.
47. Ji, Y., Pang, P. T., Feng, L., and Lu, B. (2005). Cyclic AMP controls BDNF-induced TrkB phosphorylation and dendritic spine formation in mature hippocampal neurons. Nat. Neurosci. 8, 164-172. doi: 10.1038/nn1381
48. Jiang, M., Ash, R. T., Baker, S. A., Suter, B., Ferguson, A., Park, J.,et al. (2013). Dendritic arborization and spine dynamics are abnormal in the mouse model of MECP2 duplication syndrome. J. Neurosci. 33, 19518-19533. doi: 10.1523/JNEUROSCI.1745-13.2013
49. Jugloff, D. G., Jung, B. P., Purushotham, D., Logan, R., and Eubanks, J. H. (2005). Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2.Neurobiol. Dis. 19, 18-27. doi: 10.1016/j.nbd.2004.11.002
50. Kajiya, M., Takeshita, K., Kittaka, M., Matsuda, S., Ouhara, K., Takeda, K.,et al. (2014). BDNF mimetic compound LM22A-4 regulates cementoblast differentiation via the TrkB-ERK/Akt signaling cascade. Int. Immunopharmacol.19, 245-252. doi: 10.1016/j.intimp.2014.01.028
51. Kasai, H., Fukuda, M., Watanabe, S., Hayashi-Takagi, A., and Noguchi, J. (2010). Structural dynamics of dendritic spines in memory and cognition. Trends Neurosci. 33, 121-129. doi: 10.1016/j.tins.2010.01.001
52. Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N., and Nakahara, H. (2003). Structure-stability-function relationships of dendritic spines. Trends Neurosci. 26, 360-368. doi: 10.1016/S0166-2236(03)00162-0
53. Khwaja, O. S., Ho, E., Barnes, K. V., O’Leary, H. M., Pereira, L. M., Finkelstein, Y.,et al. (2014). Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc. Natl. Acad. Sci. U.S.A. 111, 4596-4601. doi: 10.1073/pnas.1311141111
54. Kumar, V., Zhang, M. X., Swank, M. W., Kunz, J., and Wu, G. Y. (2005). Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways. J. Neurosci. 25, 11288-11299. doi: 10.1523/JNEUROSCI.2284-05.2005
55. Landi, S., Putignano, E., Boggio, E. M., Giustetto, M., Pizzorusso, T., and Ratto, G. M. (2011). The short-time structural plasticity of dendritic spines is altered in a model of Rett syndrome. Sci. Rep. 1, 45. doi: 10.1038/srep00045
56. Larimore, J. L., Chapleau, C. A., Kudo, S., Theibert, A., Percy, A. K., and Pozzo-Miller, L. (2009). Bdnf overexpression in hippocampal neurons prevents dendritic atrophy caused by Rett-associated MECP2 mutations.Neurobiol. Dis. 34, 199-211. doi: 10.1016/J.Nbd.2008.12.011
57. Levenga, J., and Willemsen, R. (2012). Perturbation of dendritic protrusions in intellectual disability. Prog. Brain Res. 197, 153-168. doi: 10.1016/B978-0-444-54299-1.00008-X
58. Li, W., Calfa, G., Larimore, J., and Pozzo-Miller, L. (2012). Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice. Proc. Natl. Acad. Sci. U.S.A. 109, 17087-17092. doi: 10.1073/pnas.1205271109
59. Luebke, J. I., Weaver, C. M., Rocher, A. B., Rodriguez, A., Crimins, J. L., Dickstein, D. L.,et al. (2010). Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models. Brain Struct. Funct. 214, 181-199. doi: 10.1007/s00429-010-0244-242
60. Luine, V., and Frankfurt, M. (2013). Interactions between estradiol, BDNF and dendritic spines in promoting memory. Neuroscience 239, 34-45. doi: 10.1016/j.neuroscience.2012.10.019
61. Marchetto, M. C., Carromeu, C., Acab, A., Yu, D., Yeo, G. W., Mu, Y.,et al. (2010). A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143, 527-539. doi: 10.1016/j.cell.2010.10.016
62. Marin-Padilla, M. (1972). Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. Brain Res. 44, 625-629. doi: 10.1016/0006-8993(72)90324-1
63. Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y.,et al. (2003). DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science 302, 890-893. doi: 10.1126/science.1090842
64. Massa, S. M., Yang, T., Xie, Y., Shi, J., Bilgen, M., Joyce, J. N.,et al. (2010). Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J. Clin. Invest. 120, 1774-1785. doi: 10.1172/JCI41356
65. Matsuzaki, M., Ellis-Davies, G. C., Nemoto, T., Miyashita, Y., Iino, M., and Kasai, H. (2001). Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat. Neurosci. 4, 1086-1092. doi: 10.1038/nn736
66. Matsuzaki, M., Honkura, N., Ellis-Davies, G. C., and Kasai, H. (2004). Structural basis of long-term potentiation in single dendritic spines. Nature 429, 761-766. doi: 10.1038/nature02617
67. McGraw, C. M., Samaco, R. C., and Zoghbi, H. Y. (2011). Adult neural function requires MeCP2. Science 333, 186. doi: 10.1126/science.1206593
68. Mizrahi, A., Crowley, J. C., Shtoyerman, E., and Katz, L. C. (2004). High-resolution in vivo imaging of hippocampal dendrites and spines. J. Neurosci. 24, 3147-3151. doi: 10.1523/JNEUROSCI.5218-03.2004
69. Moretti, P., Levenson, J. M., Battaglia, F., Atkinson, R., Teague, R., Antalffy, B.,et al. (2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J. Neurosci. 26, 319-327. doi: 10.1523/JNEUROSCI.2623-05.2006
70. Murphy, D. D., and Segal, M. (1996). Regulation of dendritic spine density in cultured rat hippocampal neurons by steroid hormones. J. Neurosci. 16, 4059-4068.
71. Nagerl, U. V., Eberhorn, N., Cambridge, S. B., and Bonhoeffer, T. (2004). Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44, 759-767. doi: 10.1016/j.neuron.2004.11.016
72. Neul, J. L., and Zoghbi, H. Y. (2004). Rett syndrome: a prototypical neurodevelopmental disorder. Neuroscientist10, 118-128. doi: 10.1177/1073858403260995
73. Nguyen, M. V., Du, F., Felice, C. A., Shan, X., Nigam, A., Mandel, G.,et al. (2012). 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. 32, 10021-10034. doi: 10.1523/JNEUROSCI.1316-12.2012
74. Nimchinsky, E. A., Sabatini, B. L., and Svoboda, K. (2002). Structure and function of dendritic spines. Annu. Rev. Physiol. 64, 313-353. doi: 10.1146/annurev.physiol.64.081501.160008
75. Nusser, Z., Lujan, R., Laube, G., Roberts, J. D., Molnar, E., and Somogyi, P. (1998). Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21, 545-559. doi: 10.1016/S0896-6273(00)80565-6
76. Ogier, M., Wang, H., Hong, E., Wang, Q., Greenberg, M. E., and Katz, D. M. (2007). Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome.J. Neurosci. 27, 10912-10917. doi: 10.1523/JNEUROSCI.1869-07.2007
77. O’Kusky, J. R., Ye, P., and D’Ercole, A. J. (2000). Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J. Neurosci. 20, 8435-8442.
78. Park, M., Salgado, J. M., Ostroff, L., Helton, T. D., Robinson, C. G., Harris, K. M.,et al. (2006). Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron 52, 817-830. doi: 10.1016/j.neuron.2006.09.040
79. Penzes, P., Cahill, M. E., Jones, K. A., Vanleeuwen, J. E., and Woolfrey, K. M. (2011a). Dendritic spine pathology in neuropsychiatric disorders. Nat. Neurosci. 14, 285-293. doi: 10.1038/nn.2741
80. Penzes, P., Woolfrey, K. M., and Srivastava, D. P. (2011b). Epac2-mediated dendritic spine remodeling: implications for disease. Mol. Cell. Neurosci. 46, 368-380. doi: 10.1016/j.mcn.2010.11.008
81. Peters, A., and Kaiserman-Abramof, I. R. (1969). The small pyramidal neuron of the rat cerebral cortex. The synapses upon dendritic spines. Z. Zellforsch. Mikrosk. Anat. 100, 487-506. doi: 10.1007/BF00344370
82. Pitcher, M. R., Ward, C. S., Arvide, E. M., Chapleau, C. A., Pozzo-Miller, L., Hoeflich, A.,et al. (2013). Insulinotropic treatments exacerbate metabolic syndrome in mice lacking MeCP2 function. Hum. Mol. Genet. 22, 2626-2633. doi: 10.1093/hmg/ddt111
83. Poo, M. M. (2001). Neurotrophins as synaptic modulators. Nat. Rev. Neurosci. 2, 24-32. doi: 10.1038/35049004
84. Purpura, D. P. (1974). Dendritic spine "dysgenesis" and mental retardation. Science 186, 1126-1128. doi: 10.1126/science.186.4169.1126
85. Qiu, Z., Sylwestrak, E. L., Lieberman, D. N., Zhang, Y., Liu, X. Y., and Ghosh, A. (2012). The Rett syndrome protein MeCP2 regulates synaptic scaling. J. Neurosci. 32, 989-994. doi: 10.1523/JNEUROSCI.0175-11.2012
86. Ramón y Cajal, S. (1888). Estructura de los centros nerviosos de las aves. Rev. Trim. Histol. Norm. Pat. 1, 1-10.
87. Ramón y Cajal, S. (1891a). Significación fisiológica de las expansiones protoplásmicas y nerviosas de la sustancia gris. Rev. De Cienc. Med. De Barc. 22, 23.
88. Ramón y Cajal, S. (1891b). Sur la structure de l’ecorce cerebrale de quelques mamiferes. La Cellule 7, 124-176.
89. Ramón y Cajal, S. (1894). La fine structure des centres nerveaux. the Croonian Lecture. Proc. R. Soc. Lond. 55, 443-468. doi: 10.1098/rspl.1894.0063
90. Ramón y Cajal, S. (1896). Les espines collaterales des cellules du cerveau colorees au bleu de methylene. Rev. Trim. Microgr. 1, 5-19.
91. Ramón y Cajal, S. (1933). Neuronismo o Reticularismo? Las Pruebas Objetivas De La Unidad Anatómica De Las Celulas Nerviosas. Madrid: Instituto Cajal.
92. Rochefort, N. L., and Konnerth, A. (2012). Dendritic spines: from structure to in vivo function. EMBO Rep. 13, 699-708. doi: 10.1038/embor.2012.102
93. Sala, C., and Segal, M. (2014). Dendritic spines: the locus of structural and functional plasticity. Physiol. Rev. 94, 141-188. doi: 10.1152/physrev.00012.2013
94. Schikorski, T., and Stevens, C. F. (1999). Quantitative fine-structural analysis of olfactory cortical synapses. Proc. Natl. Acad. Sci. U.S.A. 96, 4107-4112. doi: 10.1073/pnas.96.7.4107
95. Schmid, D. A., Yang, T., Ogier, M., Adams, I., Mirakhur, Y., Wang, Q.,et al. (2012). A TrkB small molecule partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome. J. Neurosci. 32, 1803-1810. doi: 10.1523/JNEUROSCI.0865-11.2012
96. Segal, M. (2005). Dendritic spines and long-term plasticity. Nat. Rev. Neurosci. 6, 277-284. doi: 10.1038/nrn1649
97. Shahbazian, M., Young, J., Yuva-Paylor, L., Spencer, C., Antalffy, B., Noebels, J.,et al. (2002). Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 35, 243-254. doi: 10.1016/S0896-6273(02)00768-7
98. Shirao, T., and Gonzalez-Billault, C. (2013). Actin filaments and microtubules in dendritic spines. J. Neurochem.126, 155-164. doi: 10.1111/jnc.12313
99. Simmons, D. A., Belichenko, N. P., Yang, T., Condon, C., Monbureau, M., Shamloo, M.,et al. (2013). A small molecule TrkB ligand reduces motor impairment and neuropathology in R6/2 and BACHD mouse models of Huntington’s disease. J. Neurosci. 33, 18712-18727. doi: 10.1523/JNEUROSCI.1310-13.2013
100. Smrt, R. D., Eaves-Egenes, J., Barkho, B. Z., Santistevan, N. J., Zhao, C., Aimone, J. B.,et al. (2007). Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol. Dis. 27, 77-89. doi: 10.1016/j.nbd.2007.04.005
101. Srivastava, D. P., and Penzes, P. (2011). Rapid estradiol modulation of neuronal connectivity and its implications for disease. Front. Endocrinol. (Lausanne) 2:77. doi: 10.3389/fendo.2011.00077
102. Stuss, D. P., Boyd, J. D., Levin, D. B., and Delaney, K. R. (2012). MeCP2 mutation results in compartment-specific reductions in dendritic branching and spine density in layer 5 motor cortical neurons of YFP-H mice. PLoS ONE7:e31896. doi: 10.1371/journal.pone.0031896
103. Tanaka, J., Horiike, Y., Matsuzaki, M., Miyazaki, T., Ellis-Davies, G. C., and Kasai, H. (2008). Protein synthesis and neurotrophin-dependent structural plasticity of single dendritic spines. Science 319, 1683-1687. doi: 10.1126/science.1152864
104. Trachtenberg, J. T., Chen, B. E., Knott, G. W., Feng, G., Sanes, J. R., Welker, E.,et al. (2002). Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788-794. doi: 10.1038/nature01273
105. Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., Mccurry, C., Fu, D. D.,et al. (2009). Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. Proc. Natl. Acad. Sci. U.S.A. 106, 2029-2034. doi: 10.1073/pnas.0812394106
106. Tyler, W. J., Alonso, M., Bramham, C. R., and Pozzo-Miller, L. D. (2002a). From acquisition to consolidation: on the role of brain-derived neurotrophic factor signalining in hippocampal-dependent learning. Learn. Mem. 9, 224-237. doi: 10.1101/lm.51202
107. Tyler, W. J., Perrett, S. P., and Pozzo-Miller, L. D. (2002b). The role of neurotrophins in neurotransmitter release.Neuroscientist 8, 524-531. doi: 10.1177/1073858402238511
108. Tyler, W. J., and Pozzo-Miller, L. D. (2001). BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. J. Neurosci. 21, 4249-4258.
109. Tyler, W. J., and Pozzo-Miller, L. (2003). Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones. J. Physiol. 553, 497-509. doi: 10.1113/jphysiol.2003.052639
110. Vigers, A. J., Amin, D. S., Talley-Farnham, T., Gorski, J. A., Xu, B., and Jones, K. R. (2012). Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior.Neuroscience 212, 1-18. doi: 10.1016/j.neuroscience.2012.03.031
111. Wang, H., Chan, S. A., Ogier, M., Hellard, D., Wang, Q., Smith, C.,et al. (2006). Dysregulation of brain-derived neurotrophic factor expression and neurosecretory function in Mecp2 null mice. J. Neurosci. 26, 10911-10915. doi: 10.1523/JNEUROSCI.1810-06.2006
112. Xu, X., Kozikowski, A. P., and Pozzo-Miller, L. (2014). A selective histone deacetylase-6 inhibitor improves BDNF trafficking in hippocampal neurons from Mecp2 knockout mice: implications for Rett syndrome. Front. Cell. Neurosci. 8:68. doi: 10.3389/fncel.2014.00068
113. Yuste, R. (2010). Dendritic Spines. Cambridge, MA: The MIT Press. doi: 10.7551/mitpress/9780262013505.001.0001
114. Yuste, R., and Bonhoeffer, T. (2001). Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071-1089. doi: 10.1146/annurev.neuro.24.1.1071
115. Yuste, R., Majewska, A., and Holthoff, K. (2000). From form to function: calcium compartmentalization in dendritic spines. Nat. Neurosci. 3, 653-659. doi: 10.1038/76609
116. Zeev, B. B., Bebbington, A., Ho, G., Leonard, H., De Klerk, N., Gak, E.,et al. (2009). The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome. Neurology 72, 1242-1247. doi: 10.1212/01.wnl.0000345664.72220.6a
117. Zhao, X., Pak, C., Smrt, R. D., and Jin, P. (2007). Epigenetics and Neural developmental disorders: Washington DC, September 18 and 19, 2006. Epigenetics 2, 126-134. doi: 10.4161/epi.2.2.4236
118. Zheng, W. H., and Quirion, R. (2004). Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival. J. Neurochem. 89, 844-852. doi: 10.1111/j.1471-4159.2004.02350.x
119. Zhou, Q., Homma, K. J., and Poo, M. M. (2004). Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron 44, 749-757. doi: 10.1016/j.neuron.2004.11.011
120. Zhou, Z., Hong, E. J., Cohen, S., Zhao, W. N., Ho, H. Y., Schmidt, L.,et al. (2006). Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 52, 255-269. doi: 10.1016/j.neuron.2006.09.037