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Delayed Stabilization of Dendritic Spines in Fragile X Mice
Open accessAbstract
Fragile X syndrome (FXS) causes mental impairment and autism through transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein fragile X mental retardation protein (FMRP). Cortical pyramidal neurons in affected individuals and Fmr1 knock-out (KO) mice have an increased density of dendritic spines. The mutant mice also show defects in synaptic and experience-dependent circuit plasticity, which are known to be mediated in part by dendritic spine dynamics. We used in vivo time-lapse imaging with two-photon microscopy through cranial windows in male and female neonatal mice to test the hypothesis that dynamics of dendritic protrusions are altered in KO mice during early postnatal development. We find that layer 2/3 neurons from wild-type mice exhibit a rapid decrease in dendritic spine dynamics during the first 2 postnatal weeks, as immature filopodia are replaced by mushroom spines. In contrast, KO mice show a developmental delay in the downregulation of spine turnover and in the transition from immature to mature spine subtypes. Blockade of metabotropic glutamate receptor (mGluR) signaling, which reverses some adult phenotypes of KO mice, accentuated this immature protrusion phenotype in KO mice. Thus, absence of FMRP delays spine stabilization and dysregulated mGluR signaling in FXS may partially normalize this early synaptic defect.
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“These experiments revealed that in our xenotransplantation assay, human cortical neurons show increasingly stable dendritic spine dynamics, comparable to juvenile mouse cortical neurons”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Cruz-Martín et al., 2010
In the citing paper
“Fmr1 mutant mice have a significant delay in the stabilization of dendritic spines and in the maturation of thalamocortical and corticocortical synapses 94-98 , defects associated with a temporal shift in the critical period for sensory-induced plasticity across different cortical areas 94,97,99-101 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [95]
In the citing paper
“They also show a delayed maturation of spines [75]”
From Experience-dependent structural plasticity in the cortex (2011) · cites this paper as [75]
In the citing paper
“Both studies reveal a significant increase in spine turnover in the barrel cortex of Fmr1 KO mice.”
From Experience-dependent structural plasticity in the cortex (2011) · cites this paper as [75]
In the citing paper
“For example, spines on the apical dendrites of layer 2/3 pyramidal neurons in rodent barrel cortex exhibit gradually decreasing motility (elongation and shortening of spines) and turnover rate (defined as the total amount of gains and losses of spines) between postnatal day 7 and 24 (P7-24; Lendvai et al., 2000; Cruz-Martin et al., 2010).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Cruz-Martin et al., 2010
In the citing paper
“Nevertheless, spine density continuously increases over this period of time (Cruz-Martin et al., 2010).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Cruz-Martin et al., 2010
In the citing paper
“In vivo studies further showed that in such animals spine turnover increased in various cortical areas (Cruz-Martin et al., 2010; Pan et al., 2010; Padmashri et al., 2013), and neither whisker trimming nor motor learning could further alter spine dynamics (Pan et al., 2010; Padmashri et al., 2013).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Cruz-Martin et al., 2010
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Faculty Opinions recommendation of Altered synaptic dynamics during normal brain aging.
Ziv, N. E. (2013) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.717996841.793474120
Neurodevelopmental Mechanisms of Pediatric Psychiatric Disorders
Rubeis, S. D., Roeder, K., & Devlin, B. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780190681425.003.0062
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Leigh, M. J., & Hagerman, R. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813955-4.00022-2
Schaefer, T. L., Nelson, D. L., & Erickson, C. A. (2017) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780199398911.003.0056
Effects of chronic stress on nectin1 levels in the mouse primary somatosensory cortex
Xu, X., & Wang, X. (2022) · Stress and Brain · doi:10.26599/sab.2022.9060013
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Metadata
- Authors
- Cruz-Martin, A., Crespo, M., & Portera-Cailliau, C.
- Affiliations
- Pediatrics and Genetics (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-06-09
- Volume
- 30
- Issue
- 23
- Pages
- 7793-7803
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2903441
- OpenAlex
- W2012010559
- Cited by
- 321
- References
- 80
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 14 · 2023: 15 · 2022: 18 · 2021: 24 · 2020: 25 · 2019: 19 · 2018: 18 · 2017: 24 · 2016: 27 · 2015: 23 · 2014: 34 · 2013: 28 · 2012: 16
- FWCI
- 12.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FRAXA Research Foundation
- National Institutes of Health
- National Institute of General Medical Sciences
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD054453)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- fragile X syndrome, FMRP, Fmr1 knockout mice, spine dynamics, filopodia, mushroom spines, layer 2/3 pyramidal neurons, synaptic plasticity
- MeSH terms
- Animals, Animals, Newborn, Disease Models, Animal, Fragile X Syndrome, Male, Mice, Inbred C57BL, Pseudopodia, Pyridines, Receptors, Metabotropic Glutamate, Mice, Knockout, Excitatory Amino Acid Antagonists, Dendritic Spines, Mice, Fragile X Messenger Ribonucleoprotein 1, Fragile X Mental Retardation Protein
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