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The Journal of Neuroscience, April 11, 2007, 27(15):4014-4018; doi:10.1523/JNEUROSCI.4717-06.2007

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Brief Communications
Presynaptic Fmr1 Genotype Influences the Degree of Synaptic Connectivity in a Mosaic Mouse Model of Fragile X Syndrome

Jesse E. Hanson and Daniel V. Madison

Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305

Correspondence should be addressed to Daniel V. Madison, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 003 Beckman Center, Stanford School of Medicine, Stanford, CA 94305. Email: madison{at}stanford.edu

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.

Key words: Fmr1; FMRP; mosaic; whole cell; fragile X syndrome; autism; CA3; connectivity; hippocampus; presynaptic

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Received Oct. 30, 2006; revised Feb. 21, 2007; accepted March 6, 2007.

Correspondence should be addressed to Daniel V. Madison, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 003 Beckman Center, Stanford School of Medicine, Stanford, CA 94305. Email: madison{at}stanford.edu

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