Abstract
Dendritic spines and synapses are critical for neuronal communication, and they are perturbed in many neurological disorders; however, the study of these structures in living cells has been hindered by their small size. Super resolution microscopy, unlike conventional light microscopy, is diffraction unlimited and thus is well suited for imaging small structures, such as dendritic spines and synapses. Super resolution microscopy has already revealed important new information about spine and synapse morphology, actin remodeling, and nanodomain composition in both healthy cells and diseased states. In this review, we highlight the advancements in probes that make super resolution more amenable to live-cell imaging of spines and synapses. We also discuss recent data obtained by super resolution microscopy that has advanced our knowledge of dendritic spine and synapse structure, organization, and dynamics in both healthy and diseased contexts. Finally, we propose a series of critical questions for understanding spine and synapse formation and maturation that super resolution microscopy is poised to answer.
Highlights
Dendritic spines are actin-rich protrusions on neurons that are critical for neurotransmission, as they are sites for the majority of excitatory postsynapses[1,2,3]
Barnes et al showed that animals from another mouse model for intellectual disability (SynGAP+/-) display no significant change in spine density but instead show increased spine neck length and decreased neck width, leading to increased compartmentalization, compared to WT mice[54]. They demonstrated that common physiological pathways are disrupted in the SynGAP heterozygous model and the Fragile X syndrome (FXS) model, leading to similar morphological changes in dendritic spines in both. These findings suggest that abnormalities observed in dendritic spine morphology and density in diseased states are both developmental stage and brain region specific and that these changes are the result of disruptions in pathways shared by multiple diseases
Conclusions and future directions the proper development of dendritic spines and synapses is critical for normal cognitive function, their small size has limited the acquisition of detailed images of their nanoscopic substructures via conventional light microscopy
Summary
F1000 Faculty Reviews are written by members of the prestigious F1000 Faculty. They are commissioned and are peer reviewed before publication to ensure that the final, published version is comprehensive and accessible. The reviewers who approved the final version are listed with their names and affiliations. Any comments on the article can be found at the end of the article
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