Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice.
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.
Department of Physiology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.
Emily G
EG
Harlow
Sally M
SM
Till
Theron A
TA
Russell
Lasani S
LS
Wijetunge
Peter
P
Kind
Anis
A
Contractor
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D051528:Guanylate Kinases; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D009434:Neural Pathways / Q000254:growth & development; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017470:Receptors, Glutamate / Q000502:physiology; D013003:Somatosensory Cortex / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D013788:Thalamus / Q000254:growth & development; D013997:Time Factors; D014738:Vibrissae / Q000293:injuries / Q000294:innervation
D015763:2-Amino-5-phosphonovalerate; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists; D051860:Fragile X Messenger Ribonucleoprotein 1; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017470:Receptors, Glutamate; C501447:Dlg4 protein, mouse; C497684:Fmr1 protein, mouse