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Circuit and Plasticity Defects in the Developing Somatosensory Cortex of Fmr1 Knock-Out Mice
Open accessAbstract
Silencing of the Fmr1 gene causes fragile X syndrome. Although defects in synaptic plasticity in the cerebral cortex have been linked to cognitive impairments in Fmr1 knock-out(ko) mice, the specific cortical circuits affected in the syndrome are unknown. Here, we investigated the development of excitatory projections in the barrel cortex of Fmr1 ko mice. In 2-week-old Fmr1 ko mice, a major ascending projection connecting layer 4 (L4) to L3 (L4→L3), was defective in multiple and independent ways: its strength was reduced, caused by a lower connection probability; the axonal arbors of L4 cells were spatially diffuse in L2/3; the L4→L3 projection did not show experience-dependent plasticity. By 3 weeks, the strength of the L4→L3 projection was similar to that of wild type. Our data indicate that Fmr1 shapes sensory cortical circuits during a developmental critical period.
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“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 [94]
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Metadata
- Authors
- Bureau, I., Shepherd, G. M. G., & Svoboda, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bureau, Ingrid
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-05-14
- Volume
- 28
- Issue
- 20
- Pages
- 5178-5188
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2696604
- OpenAlex
- W1966371094
- Cited by
- 201
- References
- 82
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 14 · 2019: 8 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 13 · 2014: 14 · 2013: 12 · 2012: 17
- FWCI
- 9.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- FRAXA Research Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS038259)
- 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
- FMR1 gene, fragile X syndrome, Fmr1 knockout mice, barrel cortex, somatosensory cortex, cortical circuit development, synaptic plasticity, axonal arbors, experience-dependent plasticity, critical period, connection probability
- MeSH terms
- Animals, Disease Models, Animal, Fragile X Syndrome, Male, Mice, Inbred C57BL, Nervous System Malformations, Neural Pathways, Synaptic Transmission, Neuronal Plasticity, Organ Culture Techniques, Sensation, Somatosensory Cortex, Mice, Knockout, Gene Expression Regulation, Developmental, Excitatory Postsynaptic Potentials, Genetic Predisposition to Disease, Growth Cones, Mice, Fragile X Messenger Ribonucleoprotein 1
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