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When exposed to a <jats:italic>Renilla<\/jats:italic> luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence\u2010mediated activation of its amino\u2010terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill\u2010training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice. We hypothesized that iLMO2 mediated inhibition of motoneuron activity during IT would block this enhancement. Unilateral intramuscular injections of Cre\u2010dependent AAV2\/9\u2010EF1a\u2010DIO\u2010iLMO2 (\u223c8.5 x 10<jats:sup>13<\/jats:sup> vg\/ml) were made into the gastrocnemius and tibialis anterior muscles of young female ChAT\u2010IRES\u2010Cre mice, thereby limiting iLMO2 expression specifically to their motoneurons. Four to six weeks were allowed for retrograde viral transduction after which a unilateral sciatic nerve transection (Tx) and repair was performed. Animals were randomized into four groups: IT only, IT + CTZ, CTZ only, and untreated (UT). Three weeks post Tx\u2010repair, the maximal amplitude direct muscle responses (M\u2010max) in both muscles in the IT only group were significantly greater than in UT mice, consistent with the enhancing effects of this exercise regimen. Inhibiting motoneuron activity during exercise by a single injection of CTZ, administered 30 minutes prior to exercise, completely blocked the enhancing effect of exercise. Similar treatments with CTZ in mice without iLMO2 had no effect on regeneration. Neuronal activity is required for successful enhancement of motor axon regeneration by exercise.<\/jats:p>","DOI":"10.1002\/jnr.24109","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T20:10:25Z","timestamp":1501791025000},"page":"448-457","source":"Crossref","is-referenced-by-count":24,"title":["Motoneuron activity is required for enhancements in functional recovery after peripheral nerve injury in exercised female mice"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-234X","authenticated-orcid":false,"given":"Poonam B.","family":"Jaiswal","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Emory University Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack K.","family":"Tung","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Emory University Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert 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