Altered dendritic spine function and integration in a mouse model of fragile X syndrome

Sam A. Booker, Aleksander P. F. Domanski, Owen R. Dando, Adam D. Jackson, John T. R. Isaac, Giles E. Hardingham, David J. A. Wyllie () and Peter C. Kind ()
Additional contact information
Sam A. Booker: University of Edinburgh, Hugh Robson Building, George Square
Aleksander P. F. Domanski: University of Edinburgh, Hugh Robson Building, George Square
Owen R. Dando: University of Edinburgh, Hugh Robson Building, George Square
Adam D. Jackson: University of Edinburgh, Hugh Robson Building, George Square
John T. R. Isaac: NINDS, NIH
Giles E. Hardingham: University of Edinburgh, Hugh Robson Building, George Square
David J. A. Wyllie: University of Edinburgh, Hugh Robson Building, George Square
Peter C. Kind: University of Edinburgh, Hugh Robson Building, George Square

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-11891-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11891-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-11891-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().