Subsynaptic Domains in Super-Resolution Microscopy: The Treachery of Images.

Abstract:

:The application of super-resolution optical microscopy to investigating synaptic structures has revealed a highly heterogeneous and variable intra-synaptic organization. Dense subsynaptic protein assemblies named subsynaptic domains or SSDs have been proposed as structural units that regulate the efficacy of neuronal transmission. However, an in-depth characterization of SSDs has been hampered by technical limitations of super-resolution microscopy of synapses, namely the stochasticity of the signals during the imaging procedures and the variability of the synaptic structures. Here, we synthetize the available evidence for the existence of SSDs at central synapses, as well as the possible functional relevance of SSDs. In particular, we discuss the possible regulation of co-transmission at mixed inhibitory synapses as a consequence of the subsynaptic distribution of glycine receptors (GlyRs) and GABAA receptors (GABAARs). LAY ABSTRACT Super-resolution imaging strategies bypass the resolution limit of conventional optical microscopy and have given new insights into the distribution of proteins at synapses in the central nervous system. Neurotransmitter receptors and scaffold proteins appear to occupy specialized locations within synapses that we refer to as subsynaptic domains or SSDs. Interestingly, these SSDs are highly dynamic and their formation seems to be related to the remodeling of synapses during synaptic plasticity. It was also shown that SSDs of pre-and post-synaptic proteins are aligned in so-called nanocolumns, highlighting the role of SSDs in the regulation of synaptic transmission. Despite recent advances, however, the detection of SSDs with super-resolution microscopy remains difficult due to the inherent technical limitations of these approaches that are discussed in this review article.

journal_name

Front Mol Neurosci

authors

Yang X,Specht CG

doi

10.3389/fnmol.2019.00161

subject

Has Abstract

pub_date

2019-07-02 00:00:00

pages

161

issn

1662-5099

journal_volume

12

pub_type

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