title: Presynaptic FMR1 genotype influences the degree of synaptic connectivity in a mosaic mouse model of fragile X syndrome.
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.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Jesse E
authors.initials: JE
authors.lastname: Hanson
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Madison
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000502:physiology*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000503:physiopathology*; D005838:Genotype; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017729:Presynaptic Terminals / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse