Nanoscale synapse organization and dysfunction in neurodevelopmental disorders

Hanna L Zieger, Daniel Choquet
Neurobiology of Disease. 2021-10-01; 158: 105453
DOI: 10.1016/j.nbd.2021.105453

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Zieger HL(1), Choquet D(2).

Author information:
(1)Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR
5297, F-33000 Bordeaux, France.
(2)Univ. Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR
5297, F-33000 Bordeaux, France; Univ. Bordeaux, CNRS, INSERM, Bordeaux Imaging
Center, BIC, UMS 3420, US 4, F-33000 Bordeaux, France. Electronic address:

Neurodevelopmental disorders such as those linked to intellectual disabilities or
autism spectrum disorder are thought to originate in part from genetic defects in
synaptic proteins. Single gene mutations linked to synapse dysfunction can
broadly be separated in three categories: disorders of transcriptional
regulation, disorders of synaptic signaling and disorders of synaptic scaffolding
and structures. The recent developments in super-resolution imaging technologies
and their application to synapses have unraveled a complex nanoscale organization
of synaptic components. On the one hand, part of receptors, adhesion proteins,
ion channels, scaffold elements and the pre-synaptic release machinery are
partitioned in subsynaptic nanodomains, and the respective organization of these
nanodomains has tremendous impact on synaptic function. For example, pre-synaptic
neurotransmitter release sites are partly aligned with nanometer precision to
postsynaptic receptor clusters. On the other hand, a large fraction of synaptic
components is extremely dynamic and constantly exchanges between synaptic domains
and extrasynaptic or intracellular compartments. It is largely the combination of
the exquisitely precise nanoscale synaptic organization of synaptic components
and their high dynamic that allows the rapid and profound regulation of synaptic
function during synaptic plasticity processes that underlie adaptability of brain
function, learning and memory. It is very tempting to speculate that genetic
defects that lead to neurodevelopmental disorders and target synaptic scaffolds
and structures mediate their deleterious impact on brain function through
perturbing synapse nanoscale dynamic organization. We discuss here how applying
super-resolution imaging methods in models of neurodevelopmental disorders could
help in addressing this question.

Copyright © 2021. Published by Elsevier Inc.

DOI: 10.1016/j.nbd.2021.105453
PMID: 34314857

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