Segmentation of the mouse fourth deep lumbrical muscle connectome reveals concentric organization of motor units

Theodore C Hirst, Richard R Ribchester

Research output: Contribution to journalArticlepeer-review


Connectomic analysis of the nervous system aims to discover and establish principles that underpin normal and abnormal neural connectivity and function. Here we performed image analysis of motor unit connectivity in the fourth deep lumbrical muscle (4DL) of mice, using transgenic expression of fluorescent protein in motor neurones as a morphological reporter. We developed a method that accelerated segmentation of confocal image projections of 4DL motor units, by applying high resolution (63x 1.4NA objective) imaging or deconvolution only where either proved necessary, in order to resolve axon crossings that produced ambiguities in the correct assignment of axon terminals to identified motor units imaged at lower optical resolution (40x, 1.3NA). The 4DL muscles contained between 4 and 9 motor units and motor unit sizes ranged in distribution from 3 to 111 motor nerve terminals per unit. Several structural properties of the motor units were consistent with those reported in other muscles, including suboptimal wiring length and distribution of motor unit size. Surprisingly, however, small motor units were confined to a region of the muscle near the nerve entry point, whereas their larger counterparts were progressively more widely dispersed, suggesting a previously unrecognised form of segregated motor innervation in this muscle. We also found small but significant differences in variance of motor endplate length in motor units, which correlated weakly with their motor unit size. Thus, our connectomic analysis has revealed a pattern of concentric innervation that may perhaps also exist in other, cylindrical muscles that have not previously thought to show segregated motor unit organisation. This organisation may be the outcome of competition during postnatal development based on intrinsic neuronal differences in synaptic size or synaptic strength that generates a territorial hierarchy in motor unit size and disposition.
Original languageEnglish
Pages (from-to)4859-4875
Number of pages17
JournalJournal of Physiology
Issue number19
Early online date12 Aug 2013
Publication statusPublished - 1 Oct 2013

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