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Circuit and Plasticity Defects in the Developing Somatosensory Cortex of Fmr1 Knock-Out Mice

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Bureau, Ingrid, Shepherd, Gordon M. G., Svoboda, Karel·2008·The Journal of Neuroscience

DOI 10.1523/jneurosci.1076-08.2008PMC PMC2696604

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Abstract

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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Authors: Bureau, I., Shepherd, G. M. G., & Svoboda, K.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Bureau, Ingrid
ORCID: Bureau, Ingrid
Shepherd, Gordon M. G.
Svoboda, Karel
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
DOI: 10.1523/jneurosci.1076-08.2008
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: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
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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Circuit and Plasticity Defects in the Developing Somatosensory Cortex of Fmr1 Knock-Out Mice

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