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PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits.

Published version
Peer-reviewed

Repository DOI


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Authors

Broadhead, Matthew J 
Horrocks, Mathew H 
Zhu, Fei 
Benavides-Piccione, Ruth 

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.

Description

Keywords

Animals, Disks Large Homolog 4 Protein, Electrical Synapses, Hippocampus, Mice, Mice, Knockout, Mice, Transgenic, Microscopy, Nanostructures, Protein Multimerization, Pyramidal Cells, Synaptic Transmission

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

6

Publisher

Springer Science and Business Media LLC
Sponsorship
The Royal Society (uf120277)
Medical Research Council (MR/K015850/1)
European Commission (604102)
Support from the Wellcome Trust, Medical Research Council, European Commission.