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PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits

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Broadhead_2020_SR_PSD95_CC.pdf (4.983Mb)
Date
25/04/2016
Author
Broadhead, Matthew James
Horrocks, Mathew
Zhu, Fei
Muresan, Leila
Benavides-Piccione, Ruth
DeFelipe, Javier
Fricker, David
Kopanitsa, Maksym V.
Duncan, Rory R.
Klenerman, David
Komiyama, Noboru H.
Lee, Steven F.
Grant, Seth G. N.
Keywords
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
DAS
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Abstract
The molecular features of synapses in the hippocampus underpin current models of learning and cognition. Although synapse ultra-structural diversity has been described in the canonical hippocampal circuitry, our knowledge of sub-synaptic organisation of synaptic molecules remains largely unknown. To address this, mice were engineered to express Post Synaptic Density 95 protein (PSD95) fused to either eGFP or mEos2 and imaged with two orthogonal super-resolution methods: gated stimulated emission depletion (g-STED) microscopy and photoactivated localisation microscopy (PALM). Large-scale analysis of ~100,000 synapses in 7 hippocampal sub-regions revealed they comprised discrete PSD95 nanoclusters that were spatially organised into single and multi-nanocluster PSDs. Synapses in different sub-regions, cell-types and locations along the dendritic tree of CA1 pyramidal neurons, showed diversity characterised by the number of nanoclusters per synapse. Multi-nanocluster synapses were frequently found in the CA3 and dentate gyrus sub-regions, corresponding to large thorny excrescence synapses. Although the structure of individual nanoclusters remained relatively conserved across all sub-regions, PSD95 packing into nanoclusters also varied between sub-regions determined from nanocluster fluorescence intensity. These data identify PSD95 nanoclusters as a basic structural unit, or building block, of excitatory synapses and their number characterizes synapse size and structural diversity.
Citation
Broadhead , M J , Horrocks , M , Zhu , F , Muresan , L , Benavides-Piccione , R , DeFelipe , J , Fricker , D , Kopanitsa , M V , Duncan , R R , Klenerman , D , Komiyama , N H , Lee , S F & Grant , S G N 2016 , ' PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits ' , Scientific Reports , vol. 6 , 24626 . https://doi.org/10.1038/srep24626
Publication
Scientific Reports
Status
Peer reviewed
DOI
https://doi.org/10.1038/srep24626
ISSN
2045-2322
Type
Journal article
Rights
Copyright © 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Description
Support from the Wellcome Trust, Medical Research Council, European Union Seventh Framework Programme (FP7/2007-2013) under grant agreements no. 604102 (HBP), 241995 (GENCODYS), 242498 (EUROSPIN), 242167 (SYNSYS).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20150

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