Altered structural and functional synaptic plasticity with motor skill learning in a mouse model of fragile X syndrome

Ragunathan Padmashri, Benjamin C. Reiner, Anand Suresh, Elizabeth Spartz, Anna Dunaevsky-Hutt

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS results from a mutation that causes silencing of the FMR1 gene, which encodes the fragile X mental retardation protein. Patients with FXS exhibit a range of neurological deficits, including motor skill deficits. Here, we have investigated motor skill learning and its synaptic correlates in the fmr1 knock-out (KO) mouse.Wefind that fmr1 KO mice have impaired motor skill learning of a forelimb-reaching task, compared with their wild-type (WT) littermate controls. Electrophysiological recordings from the forelimb region of the primary motor cortex demonstrated reduced, training-induced synaptic strengthening in the trained hemisphere. Moreover, long-term potentiation (LTP) is impaired in the fmr1KOmouse, and motor skill training does not occlude LTP as it does in the WT mice. Whereas motor skill training induces an increase of synaptic AMPA-type glutamate receptor subunit 1 (GluA1), there is a delay in GluA1 increase in the trained hemisphere of the fmr1KOmice. Using transcranial in vivo multiphoton microscopy, we find that fmr1 KO mice have similar spine density but increased dendritic spine turnover compared with WT mice. Finally, we report that motor skill training-induced formation of dendritic spines is impaired in fmr1 KO mice. We conclude that FMRP plays a role in motor skill learning and that reduced functional and structural synaptic plasticity might underlie the behavioral deficit in the fmr1 KO mouse.

Original languageEnglish (US)
Pages (from-to)19715-19723
Number of pages9
JournalJournal of Neuroscience
Volume33
Issue number50
DOIs
StatePublished - Dec 13 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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