Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1 knockout mice

Aaron W. Grossman, Georgina M. Aldridge, Kea Joo Lee, Michelle K. Zeman, Christine S. Jun, Humza S. Azam, Tatsuo Arii, Keiji Imoto, William T. Greenough, Im Joo Rhyu

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


Fragile X Syndrome (FXS) is the most common form of inherited mental retardation. The neuroanatomical phenotype of adult FXS patients, as well as adult Fmr1 knockout (KO) mice, includes elevated dendritic spine density and a spine morphology profile in neocortex that resembles younger individuals. Developmental studies in mouse neocortex have revealed a dynamic phenotype that varies with age, especially during the period of synaptic pruning. Here we investigated the hippocampal dentate gyrus to determine if the FXS spine phenotype is similarly tied to periods of maturation and pruning in this brain region. We used high-voltage electron microscopy to characterize Golgi-stained spines along granule cell dendrites in Fmr1 KO and wildtype (WT) mouse dentate gyrus at postnatal days 15, 21, 30, and 60. In contrast to neocortex, dendritic spine density was higher in Fmr1 KO mice across development. Interestingly, neither genotype showed specific phases of synaptogenesis or pruning, potentially explaining the phenotypic differences from neocortex. Similarly, although the KO mice showed a more immature morphological phenotype overall than WT (higher proportion of thin headed spines, lower proportion of mushroom and stubby spines), both genotypes showed gradual development, rather than impairments during specific phases of maturation. Finally, spine length showed a complex developmental pattern that differs from other brain regions examined, suggesting dynamic regulation by FMRP and other brain region-specific proteins. These findings shed new light on FMRP's role in development and highlight the need for new techniques to further understand the mechanisms by which FMRP affects synaptic maturation.

Original languageEnglish
Pages (from-to)221-227
Number of pages7
JournalBrain Research
Publication statusPublished - 2010 Oct 8

Bibliographical note

Funding Information:
This work was supported by FRAXA , NIH Grants MH35321 , HD007333 , and the Spastic Paralysis and Allied Diseases of the Central Nervous System Research Foundation . We thank David Barnard at the Resource for the Visualization of Biological Complexity at the Wadsworth Center, Albany, NY. The authors would also like to thank Kathy Bates, Julie Markham, Lisa Foster and Dack Shearer for their valuable contributions to this research.


  • Activity dependent
  • Development
  • Golgi impregnation
  • High-voltage electron microscopy
  • Hippocampus
  • Plasticity
  • Spine shape
  • Stereoscopic image

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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