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J Neurosci. 2014 Apr 30;34(18):6405-12. doi: 10.1523/JNEUROSCI.5302-13.2014.

Stimulated emission depletion (STED) microscopy reveals nanoscale defects in the developmental trajectory of dendritic spine morphogenesis in a mouse model of fragile X syndrome.

Author information

1
Patrick Wild Centre, University of Edinburgh, Edinburgh EH8 9XD, United Kingdom, Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux 33077, France, Interdisciplinary Institute for Neuroscience, Centre National de la Recherche Scientifique UMR 5297, Bordeaux 33077, France, Institut National de la Santé et de la Recherche Médicale, Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, Bordeaux 33077, France, and Centre for Brain Development and Repair, inStem, Bangalore, India.

Erratum in

  • J Neurosci. 2014 Aug 13;34(33):11173.

Abstract

Dendritic spines are basic units of neuronal information processing and their structure is closely reflected in their function. Defects in synaptic development are common in neurodevelopmental disorders, making detailed knowledge of age-dependent changes in spine morphology essential for understanding disease mechanisms. However, little is known about the functionally important fine-morphological structures, such as spine necks, due to the limited spatial resolution of conventional light microscopy. Using stimulated emission depletion microscopy (STED), we examined spine morphology at the nanoscale during normal development in mice, and tested the hypothesis that it is impaired in a mouse model of fragile X syndrome (FXS). In contrast to common belief, we find that, in normal development, spine heads become smaller, while their necks become wider and shorter, indicating that synapse compartmentalization decreases substantially with age. In the mouse model of FXS, this developmental trajectory is largely intact, with only subtle differences that are dependent on age and brain region. Together, our findings challenge current dogmas of both normal spine development as well as spine dysgenesis in FXS, highlighting the importance of super-resolution imaging approaches for elucidating structure-function relationships of dendritic spines.

KEYWORDS:

STED; dendritic spines; development; fragile X syndrome; spine dysgenesis; super-resolution microscopy

PMID:
24790210
PMCID:
PMC4004821
DOI:
10.1523/JNEUROSCI.5302-13.2014
[Indexed for MEDLINE]
Free PMC Article
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