
@article {67817,
	title = {Altered dendritic spine function and integration in a mouse model of fragile X syndrome.},
	journal = {Nat Commun},
	volume = {10},
	year = {2019},
	month = {2019 Oct 23},
	pages = {4813},
	abstract = {<p>Cellular and circuit hyperexcitability are core features of fragile X syndrome and related autism spectrum disorder models. However, the cellular and synaptic bases of this hyperexcitability have proved elusive. We report in a mouse model of fragile X syndrome, glutamate uncaging onto individual dendritic spines yields stronger single-spine excitation than wild-type, with more silent spines. Furthermore, fewer spines are required to trigger an action potential with near-simultaneous uncaging at multiple spines. This is, in part, from increased dendritic gain due to increased intrinsic excitability, resulting from reduced hyperpolarization-activated currents, and increased NMDA receptor signaling. Using super-resolution microscopy we detect no change in dendritic spine morphology, indicating no structure-function relationship at this age. However, ultrastructural analysis shows a 3-fold increase in multiply-innervated spines, accounting for the increased single-spine glutamate currents. Thus, loss of FMRP causes abnormal synaptogenesis, leading to large numbers of poly-synaptic spines despite normal spine morphology, thus explaining the synaptic perturbations underlying circuit hyperexcitability.</p>
},
	issn = {2041-1723},
	doi = {10.1038/s41467-019-11891-6},
	author = {Booker, Sam A and Domanski, Aleksander P F and Dando, Owen R and Jackson, Adam D and Isaac, John T R and Hardingham, Giles E and Wyllie, David J A and Kind, Peter C}
}
