Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome

Feng Pan; Georgina M Aldridge; William T Greenough; Wen-Biao Gan

doi:10.1073/pnas.1012496107

Back

Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome

Journal article

Open access

Peer reviewed

Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome

Feng Pan, Georgina M Aldridge, William T Greenough and Wen-Biao Gan

Proceedings of the National Academy of Sciences - PNAS, Vol.107(41), pp.17768-17773

10/12/2010

DOI: 10.1073/pnas.1012496107

PMCID: PMC2955121

PMID: 20861447

Files and links (1)

url

https://doi.org/10.1073/pnas.1012496107View

Published (Version of record) Open Access

Abstract

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by transcriptional inactivation of the X-linked fragile X mental retardation 1 ( FMR1 ) gene. FXS is associated with increased density and abnormal morphology of dendritic spines, the postsynaptic sites of the majority of excitatory synapses. To better understand how lack of the FMR1 gene function affects spine development and plasticity, we examined spine formation and elimination of layer 5 pyramidal neurons in the whisker barrel cortex of Fmr1 KO mice with a transcranial two-photon imaging technique. We found that the rates of spine formation and elimination over days to weeks were significantly higher in both young and adult KO mice compared with littermate controls. The heightened spine turnover in KO mice was due to the existence of a larger pool of “short-lived” new spines in KO mice than in controls. Furthermore, we found that the formation of new spines and the elimination of existing ones were less sensitive to modulation by sensory experience in KO mice. These results indicate that the loss of Fmr1 gene function leads to ongoing overproduction of transient spines in the primary somatosensory cortex. The insensitivity of spine formation and elimination to sensory alterations in Fmr1 KO mice suggest that the developing synaptic circuits may not be properly tuned by sensory stimuli in FXS.

Biological Sciences

mental retardation

two-photon microscopy

synaptic plasticity

imaging

autism

Details

Title: Subtitle: Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome
Creators: Feng Pan - Molecular Neurobiology Program, Skirball Institute, Department of Physiology and Neuroscience
Georgina M Aldridge - Department of Psychology and Psychiatry and Department of Cell and Developmental Biology, Beckman Institute and
William T Greenough - Department of Psychology and Psychiatry and Department of Cell and Developmental Biology, Beckman Institute and
Wen-Biao Gan - Molecular Neurobiology Program, Skirball Institute, Department of Physiology and Neuroscience
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(41), pp.17768-17773
DOI: 10.1073/pnas.1012496107
PMID: 20861447
PMCID: PMC2955121
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 10/12/2010
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020766802771

Metrics

27 Record Views

160 Times Cited - Web of Science