Stimulated emission depletion (STED) microscopy reveals nanoscale defects in the developmental trajectory of dendritic spine morphogenesis in a mouse model of fragile X syndrome
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 understandi...
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Published in | The Journal of neuroscience Vol. 34; no. 18; pp. 6405 - 6412 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Society for Neuroscience
30.04.2014
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: L.S.W., P.C.K., and U.V.N. designed research; L.S.W. and J.A. performed research; A.F. contributed unpublished reagents/analytic tools; L.S.W. analyzed data; L.S.W., J.A., A.F., P.C.K., and U.V.N. wrote the paper. P.C.K and U.V.N. contributed equally to this work. |
ISSN: | 0270-6474 1529-2401 |
DOI: | 10.1523/jneurosci.5302-13.2014 |