Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice

Neuron. 2010 Feb 11;65(3):385-98. doi: 10.1016/j.neuron.2010.01.024.


Alterations in sensory processing constitute prominent symptoms of fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory cortex during the perinatal critical period in Fmr1 knockout mice. FMRP ablation resulted in dysregulation of glutamatergic signaling maturation. The fraction of silent synapses persisting to later developmental times was increased; there was a temporal delay in the window for synaptic plasticity, while other forms of developmental plasticity were not altered in Fmr1 knockout mice. Our results indicate that FMRP is required for the normal developmental progression of synaptic maturation, and loss of this important RNA binding protein impacts the timing of the critical period for layer IV synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Age Factors
  • Animals
  • Animals, Newborn
  • Disks Large Homolog 4 Protein
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Fragile X Mental Retardation Protein / genetics*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Guanylate Kinases
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Immunoelectron / methods
  • Neural Pathways / growth & development
  • Neuronal Plasticity / physiology*
  • Patch-Clamp Techniques / methods
  • Receptors, Glutamate / physiology
  • Somatosensory Cortex / cytology*
  • Somatosensory Cortex / growth & development
  • Somatosensory Cortex / metabolism*
  • Somatosensory Cortex / ultrastructure
  • Thalamus / growth & development
  • Time Factors
  • Vibrissae / injuries
  • Vibrissae / innervation


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Excitatory Amino Acid Antagonists
  • Fmr1 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Receptors, Glutamate
  • Fragile X Mental Retardation Protein
  • 2-Amino-5-phosphonovalerate
  • Guanylate Kinases