Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome

Neurobiol Dis. 2006 Jan;21(1):217-27. doi: 10.1016/j.nbd.2005.07.005. Epub 2005 Aug 8.


Rett syndrome is an X-linked neurodevelopmental disorder caused by mutations in the gene encoding the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Here we demonstrate that the Mecp2-null mouse model of Rett syndrome shows an age-dependent impairment in hippocampal CA1 long-term potentiation induced by tetanic or theta-burst stimulation. Long-term depression induced by repetitive low-frequency stimulation is also absent in behaviorally symptomatic Mecp2-null mice. Immunoblot analyses from behaviorally symptomatic Mecp2-null mice reveal altered expression of N-methyl-d-aspartate receptor subunits NR2A and NR2B. Presynaptic function is also affected, as demonstrated by a significant reduction in paired-pulse facilitation. Interestingly, the properties of basal neurotransmission are normal in the Mecp2-null mice, consistent with our observations that the levels of expression of synaptic and cytoskeletal proteins, including glutamate receptor subunits GluR1 and GluR2, PSD95, synaptophysin-1, synaptobrevin-2, synaptotagmin-1, MAP2, betaIII-tubulin and NF200, are not significantly altered. Together, these data provide the first evidence that the loss of Mecp2 expression is accompanied by age-dependent alterations in excitatory synaptic plasticity that are likely to contribute to the cognitive and functional deficits underlying Rett syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytoskeletal Proteins / metabolism
  • Disease Models, Animal
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / physiology*
  • Long-Term Potentiation / physiology
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Methyl-CpG-Binding Protein 2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neuronal Plasticity / physiology*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Rett Syndrome / metabolism
  • Rett Syndrome / physiopathology*
  • Synaptic Transmission / physiology
  • Theta Rhythm


  • Cytoskeletal Proteins
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2
  • Receptors, N-Methyl-D-Aspartate