Abnormal development of dendritic spines in FMR1 knock-out mice

Nimchinsky, E. A., Oberlander, A. M., Svoboda, K. (July 2001) Abnormal development of dendritic spines in FMR1 knock-out mice. Journal of Neuroscience, 21 (14). pp. 5139-5146. ISSN 0270-6474

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URL: http://www.ncbi.nlm.nih.gov/pubmed/11438589

Abstract

Fragile X syndrome is caused by a mutation in the FMR1 gene leading to absence of the fragile X mental retardation protein (FMRP). Reports that patients and adult FMR1 knock-out mice have abnormally long dendritic spines of increased density suggested that the disorder might involve abnormal spine development. Because spine length, density, and motility change dramatically in the first postnatal weeks, we analyzed these properties in mutant mice and littermate controls at 1, 2, and 4 weeks of age. To label neurons, a viral vector carrying the enhanced green fluorescent protein gene was injected into the barrel cortex. Layer V neurons were imaged on a two-photon laser scanning microscope in fixed tissue sections. Analysis of >16,000 spines showed clear developmental patterns. Between 1 and 4 weeks of age, spine density increased 2.5-fold, and mean spine length decreased by 17% in normal animals. Early during cortical synaptogenesis, pyramidal cells in mutant mice had longer spines than controls. At 1 week, spine length was 28% greater in mutants than in controls. At 2 weeks, this difference was 10%, and at 4 weeks only 3%. Similarly, spine density was 33% greater in mutants than in controls at 1 week of age. At 2 or 4 weeks of age, differences were not detectable. The spine abnormality was not detected in neocortical organotypic cultures. The transient nature of the spine abnormality in the intact animal suggests that FMRP might play a role in the normal process of dendritic spine growth in coordination with the experience-dependent development of cortical circuits.

Item Type: Paper
Uncontrolled Keywords: fragile X FMRP dendritic spine critical period somatosensory cortex development mental retardation two-photon FRAGILE-X-SYNDROME MENTAL-RETARDATION PROTEIN RAT VISUAL-CORTEX CEREBRAL-CORTEX ORGANOTYPIC CULTURES PYRAMIDAL NEURONS SLICE CULTURES IN-VIVO MATURATION GOLGI
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines

diseases & disorders > congenital hereditary genetic diseases > mental retardation
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Depositing User: Matt Covey
Date: July 2001
Date Deposited: 17 Jan 2014 20:35
Last Modified: 17 Jan 2014 20:35
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29277

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