Morphological variability is greater at developing than mature mouse neuromuscular junctions.
NMJ-morph
epitrochleoanconeus
fast twitch
flexor digitorum brevis
lumbricals
morphology
motor neuron
muscle fibre type
neuromuscular junction
slow twitch
synapse
transversus abdominis
Journal
Journal of anatomy
ISSN: 1469-7580
Titre abrégé: J Anat
Pays: England
ID NLM: 0137162
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
08
04
2020
revised:
04
05
2020
accepted:
07
05
2020
pubmed:
14
6
2020
medline:
13
7
2021
entrez:
14
6
2020
Statut:
ppublish
Résumé
The neuromuscular junction (NMJ) is the highly specialised peripheral synapse formed between lower motor neuron terminals and muscle fibres. Post-synaptic acetylcholine receptors (AChRs), which are found in high density in the muscle membrane, bind to acetylcholine released into the synaptic cleft of the NMJ, thereby enabling the conversion of motor action potentials to muscle contractions. NMJs have been studied for many years as a general model for synapse formation, development and function, and are known to be early sites of pathological changes in many neuromuscular diseases. However, information is limited on the diversity of NMJs in different muscles, how synaptic morphology changes during development, and the relevance of these parameters to neuropathology. Here, this crucial gap was addressed using a robust and standardised semi-automated workflow called NMJ-morph to quantify features of pre- and post-synaptic NMJ architecture in an unbiased manner. Five wholemount muscles from wild-type mice were dissected and compared at immature (post-natal day, P7) and early adult (P31-32) timepoints. The inter-muscular variability was greater in mature post-synaptic AChR morphology than that of the pre-synaptic motor neuron terminal. Moreover, the developing NMJ showed greater differences across muscles than the mature synapse, perhaps due to the observed distinctions in synaptic growth between muscles. Nevertheless, the amount of nerve to muscle contact was consistent, suggesting that pathological denervation can be reliably compared across different muscles in mouse models of neurodegeneration. Additionally, mature post-synaptic endplate diameters correlated with fibre type, independently of muscle fibre diameter. Altogether, this work provides detailed information on healthy pre- and post-synaptic NMJ morphology from five anatomically and functionally distinct mouse muscles, delivering useful reference data for future comparison with neuromuscular disease models.
Identifiants
pubmed: 32533580
doi: 10.1111/joa.13228
pmc: PMC7495279
doi:
Substances chimiques
Receptors, Cholinergic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
603-617Subventions
Organisme : Medical Research Council
ID : MR/S006990/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107116/Z/15/Z
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.
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