Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice.
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.
Bureau
Ingrid
I
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ingrid.bureau@inmed.univ-mrs.fr
Shepherd
Gordon M G
GM
Svoboda
Karel
K
D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D020439:Growth Cones / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009421:Nervous System Malformations / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009434:Neural Pathways / Q000002:abnormalities / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D012677:Sensation / Q000235:genetics; D013003:Somatosensory Cortex / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse