Presynaptic FMR1 genotype influences the degree of synaptic connectivity in a mosaic mouse model of fragile X syndrome

J Neurosci. 2007 Apr 11;27(15):4014-8. doi: 10.1523/JNEUROSCI.4717-06.2007.

Abstract

Almost all female and some male fragile X syndrome (FXS) patients are mosaic for expression of the FMR1 gene, yet all research in models of FXS has been in animals uniformly lacking Fmr1 expression. Therefore, we developed a system allowing neuronal genotype to be visualized in vitro in mouse brain slices mosaic for Fmr1 expression. Whole-cell recordings from individual pairs of presynaptic and postsynaptic neurons in organotypic hippocampal slices were used to probe the cell-autonomous effects of Fmr1 genotype in mosaic networks. These recordings revealed that wild-type presynaptic neurons formed synaptic connections at a greater rate than presynaptic neurons lacking normal Fmr1 function in mosaic networks. At the same time, the postsynaptic Fmr1 genotype did not influence the probability that a neuron received synaptic connections. Asymmetric presynaptic function during development of the brain could result in a decreased participation in network function by the portion of neurons lacking FMR1 expression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Fragile X Mental Retardation Protein / physiology*
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / physiopathology*
  • Genotype
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Mice, Transgenic
  • Presynaptic Terminals / physiology*
  • Synapses / physiology

Substances

  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein