Delayed Stabilization of Dendritic Spines in Fragile X Mice
- 9 June 2010
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (23), 7793-7803
- https://doi.org/10.1523/jneurosci.0577-10.2010
Abstract
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.This publication has 77 references indexed in Scilit:
- Rapid Functional Maturation of Nascent Dendritic SpinesNeuron, 2009
- Fragile X Syndrome: Loss of Local mRNA Regulation Alters Synaptic Development and FunctionNeuron, 2008
- Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO miceNeurobiology of Disease, 2008
- EphB Receptors Couple Dendritic Filopodia Motility to Synapse FormationNeuron, 2008
- Correction of Fragile X Syndrome in MiceNeuron, 2007
- Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapsesMolecular and Cellular Neuroscience, 2006
- Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEPNeuropharmacology, 2005
- The mGluR theory of fragile X mental retardationTrends in Neurosciences, 2004
- Genesis of dendritic spines: insights from ultrastructural and imaging studiesNature Reviews Neuroscience, 2004
- Reduced Cortical Synaptic Plasticity and GluR1 Expression Associated with Fragile X Mental Retardation Protein DeficiencyMolecular and Cellular Neuroscience, 2002