Abstract
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 language | English |
|---|---|
| Pages (from-to) | 221-227 |
| Number of pages | 7 |
| Journal | Brain Research |
| Volume | 1355 |
| DOIs | |
| Publication status | Published - 2010 Oct 8 |
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Keywords
- Activity dependent
- Development
- Golgi impregnation
- High-voltage electron microscopy
- Hippocampus
- Plasticity
- Spine shape
- Stereoscopic image
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1 knockout mice. / Grossman, Aaron W.; Aldridge, Georgina M.; Lee, Kea Joo; Zeman, Michelle K.; Jun, Christine S.; Azam, Humza S.; Arii, Tatsuo; Imoto, Keiji; Greenough, William T.; Rhyu, Im Joo.
In: Brain Research, Vol. 1355, 08.10.2010, p. 221-227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Developmental characteristics of dendritic spines in the dentate gyrus of Fmr1 knockout mice
AU - Grossman, Aaron W.
AU - Aldridge, Georgina M.
AU - Lee, Kea Joo
AU - Zeman, Michelle K.
AU - Jun, Christine S.
AU - Azam, Humza S.
AU - Arii, Tatsuo
AU - Imoto, Keiji
AU - Greenough, William T.
AU - Rhyu, Im Joo
PY - 2010/10/8
Y1 - 2010/10/8
N2 - 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.
AB - 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.
KW - Activity dependent
KW - Development
KW - Golgi impregnation
KW - High-voltage electron microscopy
KW - Hippocampus
KW - Plasticity
KW - Spine shape
KW - Stereoscopic image
UR - http://www.scopus.com/inward/record.url?scp=77956619092&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956619092&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2010.07.090
DO - 10.1016/j.brainres.2010.07.090
M3 - Article
VL - 1355
SP - 221
EP - 227
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -