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[S21]: Presynaptic and axonal expression of the Fragile X mental retardation protein in the developing and regenerating CNS
Author(s) -
Christie S.B.,
Schwob J.,
Fallon J.R.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.026
Subject(s) - fragile x , citation , library science , neuroscience , psychology , biology , computer science , genetics , gene
In patients with Fragile X syndrome the fmr1 gene is silenced, leading to a lack of expression of the protein FMRP. The fmr1 knock-out ( fmr1-KO) is an excellent model for this developmental disorder. Previous studies, have suggested that the mechanisms of synaptic plasticity are altered in these mice: LTD is enhanced in the hippocampus and cerebellum, while LTP is reduced in the neocortex. However, how these changes relate to changes in neuronal circuits is unknown. Defects in developmental synaptic plasticity could change the synaptic strength of specific projections and could also perturb synaptic stabilization/elimination. We analyzed the circuit development and developmental circuit plasticity of intracortical projections in the barrel cortex of fmr1-KOmice. Tomeasure the structure of functional circuits we used laser scanning photo-stimulation. This technique measures the spatial distribution of presynaptic excitatory neurons of individual postsynaptic cells and hence, the structure of excitatory circuits.At postnatal days (PND)13–15, the excitatory projections from layer (L) 4 stellate cells to L3 pyramidal cells located above barrels in L3 were weaker in fmr1-KO mice compare to their wt littermates. This circuit defect was accompanied by an abnormal morphology of L4 stellate cell axons,which formed spatially less focused forwardprojections in the fmr1-KO mice. Both, the circuit and structural phenotypes were developmentally transient and were highly attenuated by PND 19–22. We also studied experience-dependent plasticity induced by whisker trimming. In wild-type mice, early sensory deprivation induced a weakening of the L4! L3 projections and, simultaneously, a strengthening of the L5A! L3 projections. In fmr1-KO mice, the weakening of L4! L3 projections was abolished while the strengthening of L5A! L3 projections was maintained. These results demonstrate the importance of FMRP for the normal development and plasticity of specific synaptic projections, and suggest that altered neocortical circuits underlie the Fragile X syndrome.