Stimulated emission depletion (STED) microscopy reveals nanoscale defects in the developmental trajectory of dendritic spine morphogenesis in a mouse model of fragile X syndrome.
Journal of Neuroscience. 2014-04-30; 34(18): 6405-6412
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1. 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.
Wijetunge LS(1), Angibaud J, Frick A, Kind PC, Nägerl UV.
(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,
J Neurosci. 2014 Aug 13;34(33):11173.
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.
PMID: 24790210 [Indexed for MEDLINE]