title: Experience-dependent retinogeniculate synapse remodeling is abnormal in MeCP2-deficient mice.
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.
authors.affiliation: Department of Neurology, F.M. Kirby Neurobiology Center, Children's Hospital, Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Joao
authors.initials: J
authors.lastname: Noutel
authors.forename: Y Kate
authors.initials: YK
authors.lastname: Hong
authors.forename: Byunghee
authors.initials: B
authors.lastname: Leu
authors.forename: Erin
authors.initials: E
authors.lastname: Kang
authors.forename: Chinfei
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D003624:Darkness / Q000009:adverse effects; D005260:Female; D005829:Geniculate Bodies / Q000378:metabolism / Q000473:pathology*; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012683:Sensory Deprivation / Q000502:physiology; D013569:Synapses / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009435:Synaptic Transmission / Q000235:genetics; D014796:Visual Perception / Q000235:genetics
chemical_list: D051783:Methyl-CpG-Binding Protein 2