Neurobiology of Disease 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 (L43L3), 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 L43L3 projection did not show experience-dependent plasticity. By 3weeks, the strength of the L43L3 projectionwas similar to that of wild type. Our data indicate that Fmr1 shapes sensory cortical circuits during a developmental critical period. Key words: barrel; cortex; development; network; neuron; plasticit