Microcircuit formation following transplantation of mouse embryonic stem cell-derived neurons in peripheral nerve

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 rhyth...

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Bibliographic Details
Published in:Journal of neurophysiology 2017-04, Vol.117 (4), p.1683-1689
Main Authors: Magown, Philippe, Rafuse, Victor F, Brownstone, Robert M
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Animals
Electric Stimulation - methods
Embryo, Mammalian
Mice
Mice, Inbred C57BL
Motor Neurons - physiology
Mouse Embryonic Stem Cells - physiology
Mouse Embryonic Stem Cells - transplantation
Muscle, Skeletal - innervation
Nerve Net - physiology
Nerve Regeneration - physiology
Neurotransmitter Agents - pharmacology
Peripheral Nerve Injuries - surgery
Rapid Report
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Summary: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. 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.
ISSN:0022-3077
1522-1598
DOI:10.1152/jn.00943.2016