Defects in the developing cortical circuits of fmr1 mutant mice

Bureau, I., Shepherd, G., Svoboda, K. (December 2006) Defects in the developing cortical circuits of fmr1 mutant mice. International Journal of Developmental Neuroscience, 24 (8). p. 480. ISSN 0736-5748

URL: https://www.sciencedirect.com/science/article/pii/...
DOI: 10.1016/j.ijdevneu.2006.09.025

Abstract

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-KO mice. To measure 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 forward projections 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.

Item Type: Paper
Additional Information: Meeting Abstract
Subjects: Investigative techniques and equipment > optical devices > lasers > quantitative laser scanning photostimulation
organs, tissues, organelles, cell types and functions > tissues types and functions > barrel cortex
diseases & disorders > congenital hereditary genetic diseases > fragile X syndrome
Publication Type > Meeting Abstract
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > neural plasticity
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Depositing User: CSHL Librarian
Date: December 2006
Date Deposited: 21 Dec 2011 15:30
Last Modified: 11 Sep 2018 20:33
URI: http://repository.cshl.edu/id/eprint/22763

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