Environmental Enrichment Reveals Effects of Genotype on Hippocampal Spine Morphologies in the Mouse Model of Fragile X Syndrome

Cereb Cortex. 2015 Feb;25(2):516-27. doi: 10.1093/cercor/bht249. Epub 2013 Sep 17.


Fragile X Syndrome (FXS) and the Fmr1 knockout (KO) mouse model of this disorder exhibit abnormal dendritic spines in neocortex, but the degree of spine disturbances in hippocampus is not clear. The present studies tested if the mutation influences dendritic branching and spine measures for CA1 pyramidal cells in Fmr1 KO and wild-type (WT) mice provided standard or enriched environment (EE) housing. Automated measures from 3D reconstructions of green fluorescent protein (GFP)-labeled cells showed that spine head volumes were ∼ 40% lower in KOs when compared with WTs in both housing conditions. With standard housing, average spine length was greater in KOs versus WTs but there was no genotype difference in dendritic branching, numbers of spines, or spine length distribution. However, with EE rearing, significant effects of genotype emerged including greater dendritic branching in WTs, greater spine density in KOs, and greater numbers of short thin spines in KOs when compared with WTs. Thus, EE rearing revealed greater effects of the Fmr1 mutation on hippocampal pyramidal cell morphology than was evident with standard housing, suggesting that environmental enrichment allows for fuller appreciation of the impact of the mutation and better representation of abnormalities likely to be present in human FXS.

Keywords: 3D reconstruction; dendritic spine; enriched environment; fragile x syndrome; hippocampus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dendritic Spines / pathology*
  • Disease Models, Animal
  • Environment*
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Mental Retardation Protein / metabolism
  • Fragile X Syndrome / pathology*
  • Fragile X Syndrome / therapy*
  • Genotype
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / pathology*
  • Housing, Animal
  • Imaging, Three-Dimensional
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Pyramidal Cells / pathology*


  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein
  • Green Fluorescent Proteins