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The Journal of Neuroscience, May 14, 2008, 28(20):5178-5188; doi:10.1523/JNEUROSCI.1076-08.2008

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

Ingrid Bureau,¹ Gordon M. G. Shepherd,^1,2 and Karel Svoboda^1,3

¹Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, ²Department of Physiology, Northwestern University, Chicago, Illinois 60611, and ³Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147

Correspondence should be addressed to Ingrid Bureau at her present address: Institut de Neurobiologie de la Méditerranée, 163 route de Luminy, BP 13, 13273 Marseille, France. Email: ingrid.bureau{at}inmed.univ-mrs.fr

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 (L4L3), 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 L4L3 projection did not show experience-dependent plasticity. By 3 weeks, the strength of the L4L3 projection was 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; plasticity

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Received May 25, 2007; accepted March 17, 2008.

Correspondence should be addressed to Ingrid Bureau at her present address: Institut de Neurobiologie de la Méditerranée, 163 route de Luminy, BP 13, 13273 Marseille, France. Email: ingrid.bureau{at}inmed.univ-mrs.fr

This article has been cited by other articles:

				I. Bureau The development of cortical columns: role of Fragile X mental retardation protein J. Physiol., May 1, 2009; 587(9): 1897 - 1901. [Abstract] [Full Text] [PDF]

				Y. Pilpel, A. Kolleker, S. Berberich, M. Ginger, A. Frick, E. Mientjes, B. A. Oostra, and P. H. Seeburg Synaptic ionotropic glutamate receptors and plasticity are developmentally altered in the CA1 field of Fmr1 knockout mice J. Physiol., February 15, 2009; 587(4): 787 - 804. [Abstract] [Full Text] [PDF]

				J. R. Gibson, A. F. Bartley, S. A. Hays, and K. M. Huber Imbalance of Neocortical Excitation and Inhibition and Altered UP States Reflect Network Hyperexcitability in the Mouse Model of Fragile X Syndrome J Neurophysiol, November 1, 2008; 100(5): 2615 - 2626. [Abstract] [Full Text] [PDF]

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