RT Journal Article SR Electronic T1 Stimulated Emission Depletion (STED) Microscopy Reveals Nanoscale Defects in the Developmental Trajectory of Dendritic Spine Morphogenesis in a Mouse Model of Fragile X Syndrome JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6405 OP 6412 DO 10.1523/JNEUROSCI.5302-13.2014 VO 34 IS 18 A1 Lasani S. Wijetunge A1 Julie Angibaud A1 Andreas Frick A1 Peter C. Kind A1 U. Valentin Nägerl YR 2014 UL http://www.jneurosci.org/content/34/18/6405.abstract AB 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.