Abstract
Motoneurons derived from embryonic stem cells can be transplanted in the tibial nerve, where they extend axons to functionally innervate target muscle. Here, we studied spontaneous muscle contractions in these grafts 3 mo following transplantation. One-half of the transplanted grafts generated rhythmic muscle contractions of variable patterns, either spontaneously or in response to brief electrical stimulation. Activity generated by transplanted embryonic stem cell-derived neurons was driven by glutamate and was modulated by muscarinic and GABAergic/glycinergic transmission. Furthermore, rhythmicity was promoted by the same transmitter combination that evokes rhythmic locomotor activity in spinal cord circuits. These results demonstrate that there is a degree of self-assembly of microcircuits in these peripheral grafts involving embryonic stem cell-derived motoneurons and interneurons. Such spontaneous activity is reminiscent of embryonic circuit development in which spontaneous activity is essential for proper connectivity and function and may be necessary for the grafts to form functional connections with muscle. NEW & NOTEWORTHY This manuscript demonstrates that, following peripheral transplantation of neurons derived from embryonic stem cells, the grafts are spontaneously active. The activity is produced and modulated by a number of transmitter systems, indicating that there is a degree of self-assembly of circuits in the grafts.
Original language | English |
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Pages (from-to) | 1683-1689 |
Number of pages | 7 |
Journal | Journal of Neurophysiology |
Volume | 117 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 4 2017 |
Bibliographical note
Funding Information:P. Magown was supported by a Canadian Institutes of Health Research (CIHR) doctoral fellowship award. This work was funded by the Natural Sciences and Engineering Research Council (V. F. Rafuse), CIHR Neuromuscular Research Partnership (V. F. Rafuse), and CIHR (FRN 74633; R. M. Brownstone). This research was also undertaken, in part, thanks to funding from the Canada Research Chairs program (R. M. Brownstone).
Publisher Copyright:
© 2017 the American Physiological Society.
ASJC Scopus Subject Areas
- General Neuroscience
- Physiology
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't