Experience-dependent Retinogeniculate Synapse Remodeling is Abnormal in MeCP2-deficient Mice

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2011 Apr 13

PMID 21482354

Citations 73

Authors

Joao Noutel

Y Kate Hong

Byunghee Leu

Erin Kang

Chinfei Chen

Affiliations

Soon will be listed here.

Abstract

Mutations in MECP2 underlie the neurodevelopmental disorder Rett syndrome (RTT). One hallmark of RTT is relatively normal development followed by a later onset of symptoms. Growing evidence suggests an etiology of disrupted synaptic function, yet it is unclear how these abnormalities explain the clinical presentation of RTT. Here we investigate synapse maturation in Mecp2-deficient mice at a circuit with distinct developmental phases: the retinogeniculate synapse. We find that synapse development in mutants is comparable to that of wild-type littermates between postnatal days 9 and 21, indicating that initial phases of synapse formation, elimination, and strengthening are not significantly affected by MeCP2 absence. However, during the subsequent experience-dependent phase of synapse remodeling, the circuit becomes abnormal in mutants as retinal innervation of relay neurons increases and retinal inputs fail to strengthen further. Moreover, synaptic plasticity in response to visual deprivation is disrupted in mutants. These results suggest a crucial role for Mecp2 in experience-dependent refinement of synaptic circuits.

Citing Articles

A novel developmental critical period of orexinergic signaling in the primary visual thalamus.

Sanetra A, Jeczmien-Lazur J, Pradel K, Klich J, Palus-Chramiec K, Janik M iScience. 2024; 27(7):110352.

PMID: 39055917 PMC: 11269934. DOI: 10.1016/j.isci.2024.110352.

Activity-induced MeCP2 phosphorylation regulates retinogeniculate synapse refinement.

Tzeng C, Whitwam T, Boxer L, Li E, Silberfeld A, Trowbridge S Proc Natl Acad Sci U S A. 2023; 120(44):e2310344120.

PMID: 37871205 PMC: 10623012. DOI: 10.1073/pnas.2310344120.

Selective Deletion of Methyl CpG Binding Protein 2 from Parvalbumin Interneurons in the Auditory Cortex Delays the Onset of Maternal Retrieval in Mice.

Rupert D, Pagliaro A, Choe J, Shea S J Neurosci. 2023; 43(40):6745-6759.

PMID: 37625856 PMC: 10552946. DOI: 10.1523/JNEUROSCI.0838-23.2023.

Activity-Dependent Synapse Refinement: From Mechanisms to Molecules.

Nagappan-Chettiar S, Burbridge T, Umemori H Neuroscientist. 2023; 30(6):673-689.

PMID: 37140155 PMC: 11584027. DOI: 10.1177/10738584231170167.

Wild-type MECP2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome.

Mykins M, Layo-Carris D, Dunn L, Skinner D, McBryar A, Perez S J Neurosci Res. 2023; 101(8):1236-1258.

PMID: 37026482 PMC: 10332853. DOI: 10.1002/jnr.25190.

References

Jaubert-Miazza L, Green E, Lo F, Bui K, Mills J, Guido W . Structural and functional composition of the developing retinogeniculate pathway in the mouse. Vis Neurosci. 2005; 22(5):661-76. DOI: 10.1017/S0952523805225154. View

Monteggia L, Kavalali E . Rett syndrome and the impact of MeCP2 associated transcriptional mechanisms on neurotransmission. Biol Psychiatry. 2008; 65(3):204-10. PMC: 3001289. DOI: 10.1016/j.biopsych.2008.10.036. View

Skene P, Illingworth R, Webb S, Kerr A, James K, Turner D . Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell. 2010; 37(4):457-68. PMC: 4338610. DOI: 10.1016/j.molcel.2010.01.030. View

von Tetzchner S, Jacobsen K, Smith L, Skjeldal O, Heiberg A, Fagan J . Vision, cognition and developmental characteristics of girls and women with Rett syndrome. Dev Med Child Neurol. 1996; 38(3):212-25. DOI: 10.1111/j.1469-8749.1996.tb15083.x. View

Bader G, Hagberg B . Neurophysiological findings in the Rett syndrome, II: Visual and auditory brainstem, middle and late evoked responses. Brain Dev. 1989; 11(2):110-4. DOI: 10.1016/s0387-7604(89)80078-6. View

Armstrong D, Deguchi K, Antallfy B . Survey of MeCP2 in the Rett syndrome and the non-Rett syndrome brain. J Child Neurol. 2003; 18(10):683-7. DOI: 10.1177/08830738030180100601. View

Shahbazian M, Antalffy B, Armstrong D, Zoghbi H . Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation. Hum Mol Genet. 2002; 11(2):115-24. DOI: 10.1093/hmg/11.2.115. View

Zhang Z, Zak J, Liu H . MeCP2 is required for normal development of GABAergic circuits in the thalamus. J Neurophysiol. 2010; 103(5):2470-81. PMC: 2867574. DOI: 10.1152/jn.00601.2009. View

Asaka Y, Jugloff D, Zhang L, Eubanks J, Fitzsimonds R . Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2005; 21(1):217-27. DOI: 10.1016/j.nbd.2005.07.005. View

10.

Bureau I, Shepherd G, Svoboda K . Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice. J Neurosci. 2008; 28(20):5178-88. PMC: 2696604. DOI: 10.1523/JNEUROSCI.1076-08.2008. View

11.

Chao H, Chen H, Samaco R, Xue M, Chahrour M, Yoo J . Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes. Nature. 2010; 468(7321):263-9. PMC: 3057962. DOI: 10.1038/nature09582. View

12.

Lewis J, Meehan R, Henzel W, Jeppesen P, Klein F, Bird A . Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell. 1992; 69(6):905-14. DOI: 10.1016/0092-8674(92)90610-o. View

13.

Demas J, Sagdullaev B, Green E, Jaubert-Miazza L, McCall M, Gregg R . Failure to maintain eye-specific segregation in nob, a mutant with abnormally patterned retinal activity. Neuron. 2006; 50(2):247-59. DOI: 10.1016/j.neuron.2006.03.033. View

14.

Hooks B, Chen C . Vision triggers an experience-dependent sensitive period at the retinogeniculate synapse. J Neurosci. 2008; 28(18):4807-17. PMC: 2793334. DOI: 10.1523/JNEUROSCI.4667-07.2008. View

15.

Stauder J, Smeets E, van Mil S, Curfs L . The development of visual- and auditory processing in Rett syndrome: an ERP study. Brain Dev. 2006; 28(8):487-94. DOI: 10.1016/j.braindev.2006.02.011. View

16.

Chahrour M, Jung S, Shaw C, Zhou X, Wong S, Qin J . MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008; 320(5880):1224-9. PMC: 2443785. DOI: 10.1126/science.1153252. View

17.

Ziburkus J, Dilger E, Lo F, Guido W . LTD and LTP at the developing retinogeniculate synapse. J Neurophysiol. 2009; 102(6):3082-90. PMC: 2804430. DOI: 10.1152/jn.90618.2008. View

18.

Tao J, Hu K, Chang Q, Wu H, Sherman N, Martinowich K . Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function. Proc Natl Acad Sci U S A. 2009; 106(12):4882-7. PMC: 2660725. DOI: 10.1073/pnas.0811648106. View

19.

Wood L, Gray N, Zhou Z, Greenberg M, Shepherd G . Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in an RNA interference model of methyl-CpG-binding protein 2 deficiency. J Neurosci. 2009; 29(40):12440-8. PMC: 2782478. DOI: 10.1523/JNEUROSCI.3321-09.2009. View

20.

Guy J, Hendrich B, Holmes M, Martin J, Bird A . A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet. 2001; 27(3):322-6. DOI: 10.1038/85899. View