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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Disease Models, Animal
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Excitatory Postsynaptic Potentials / genetics
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Fragile X Mental Retardation Protein / genetics*
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Fragile X Syndrome / genetics
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Fragile X Syndrome / metabolism
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Fragile X Syndrome / physiopathology
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Gene Expression Regulation, Developmental / genetics
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Genetic Predisposition to Disease / genetics*
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Growth Cones / metabolism
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Growth Cones / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nervous System Malformations / genetics
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Nervous System Malformations / metabolism
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Nervous System Malformations / physiopathology*
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Neural Pathways / abnormalities
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Neural Pathways / metabolism
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Neural Pathways / physiopathology
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Neuronal Plasticity / genetics*
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Organ Culture Techniques
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Sensation / genetics
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Somatosensory Cortex / abnormalities*
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Somatosensory Cortex / metabolism
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Somatosensory Cortex / physiopathology*
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Synaptic Transmission / genetics
Substances
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Fmr1 protein, mouse
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Fragile X Mental Retardation Protein