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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 107; no. 41; pp. 17768 - 17773
• Main Authors: Pan, Feng, Aldridge, Georgina M., Greenough, William T., Gan, Wen-Biao
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 12.10.2010; National Acad Sciences
• Subjects: Animals; Biological Sciences; Chessboards; Dendrites; Dendritic spines; Dendritic Spines - metabolism; Dendritic Spines - physiology; Diagnostic Imaging - methods; Fragile X Mental Retardation Protein - genetics; Fragile X syndrome; Fragile X Syndrome - metabolism; Fragile X Syndrome - physiopathology; Genes; Imaging; Intellectual disability; Male; Mental retardation; Mice; Mice, Inbred C57BL; Mice, Knockout; Neck; Neurons; Rodents; Sense impressions; Somatosensory cortex; Spine; Synapses - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1012496107

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.