title: NMJ-morph reveals principal components of synaptic morphology influencing structure-function relationships at the neuromuscular junction.
abstract: The ability to form synapses is one of the fundamental properties required by the mammalian nervous system to generate network connectivity. Structural and functional diversity among synaptic populations is a key hallmark of network diversity, and yet we know comparatively little about the morphological principles that govern variability in the size, shape and strength of synapses. Using the mouse neuromuscular junction (NMJ) as an experimentally accessible model synapse, we report on the development of a robust, standardized methodology to facilitate comparative morphometric analysis of synapses ('NMJ-morph'). We used NMJ-morph to generate baseline morphological reference data for 21 separate pre- and post-synaptic variables from 2160 individual NMJs belonging to nine anatomically distinct populations of synapses, revealing systematic differences in NMJ morphology between defined synaptic populations. Principal components analysis revealed that overall NMJ size and the degree of synaptic fragmentation, alongside pre-synaptic axon diameter, were the most critical parameters in defining synaptic morphology. 'Average' synaptic morphology was remarkably conserved between comparable synapses from the left and right sides of the body. Systematic differences in synaptic morphology predicted corresponding differences in synaptic function that were supported by physiological recordings, confirming the robust relationship between synaptic size and strength.
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Anatomy, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Ross A
authors.initials: RA
authors.lastname: Jones
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Anatomy, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Caitlan D
authors.initials: CD
authors.lastname: Reich
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Kosala N
authors.initials: KN
authors.lastname: Dissanayake
authors.affiliation: Anatomy, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Fanney
authors.initials: F
authors.lastname: Kristmundsdottir
authors.affiliation: Anatomy, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Findlater
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Ribchester
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Simmen
authors.affiliation: Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK t.gillingwater@ed.ac.uk.|Centre for Integrative Physiology, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.|Anatomy, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Old Medical School, Teviot Place, Edinburgh EH8 9XD, UK.
authors.forename: Thomas H
authors.identifier: 0000-0002-0306-5577
authors.initials: TH
authors.lastname: Gillingwater
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000502:physiology*; D025341:Principal Component Analysis; D013569:Synapses / Q000502:physiology*
keywords: NMJ-morph; morphology; neuromuscular junction; statistical modelling; synapse