Nanostructural Diversity of Synapses in the Mammalian Spinal Cord

Matthew J. Broadhead, Calum Bonthron, Lauren Arcinas, Sumi Bez, Fei Zhu, Frances Goff, Jonathan Nylk, Kishan Dholakia, Frank Gunn-Moore, Seth G.N. Grant, Gareth B. Miles

Research output: Contribution to journalArticlepeer-review

Abstract

Functionally distinct synapses exhibit diverse and complex organisation at molecular and nanoscale levels. Synaptic diversity may be dependent on developmental stage, anatomical locus and the neural circuit within which synapses reside. Furthermore, astrocytes, which align with pre and post-synaptic structures to form ‘tripartite synapses’, can modulate neural circuits and impact on synaptic organisation. In this study, we aimed to determine which factors impact the diversity of excitatory synapses throughout the lumbar spinal cord. We used PSD95-eGFP mice, to visualise excitatory postsynaptic densities (PSDs) using high-resolution and super-resolution microscopy. We reveal a detailed and quantitative map of the features of excitatory synapses in the lumbar spinal cord, detailing synaptic diversity that is dependent on developmental stage, anatomical region and whether associated with VGLUT1 or VGLUT2 terminals. We report that PSDs are nanostructurally distinct between spinal laminae and across age groups. PSDs receiving VGLUT1 inputs also show enhanced nanostructural complexity compared with those receiving VGLUT2 inputs, suggesting pathway-specific diversity. Finally, we show that PSDs exhibit greater nanostructural complexity when part of tripartite synapses, and we provide evidence that astrocytic activation enhances PSD95 expression. Taken together, these results provide novel insights into the regulation and diversification of synapses across functionally distinct spinal regions and advance our general understanding of the ‘rules’ governing synaptic nanostructural organisation.

Original languageEnglish
Article number8189
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - 2020 Dec 1

Bibliographical note

Funding Information:
This work for funded by the Biotechnology and Biological Sciences Research Council (BBSRC; BB/M021793/1), RS MacDonald Charitable Trust, Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), the Engineering and Physical Sciences Research Council (EPSRC; EP/P030017/1), Welcome Trust (202932/Z/16/Z), European Research Council (ERC; 695568) and the Simons Initiative for the Developing Brain. We would also like thank Dr Alison Dun of the Edinburgh Super-Resolution Imaging Consortium (ESRIC) for assistance and support with the g-STED imaging.

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • General

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