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We hypothesized that activation of excitatory (Gq) <jats:styled-content style=\"fixed-case\">DREADD<\/jats:styled-content> by its designer ligand, clozapine\u2010N\u2010oxide (<jats:styled-content style=\"fixed-case\">CNO<\/jats:styled-content>), would increase the excitability of neurons whose axons have been transected following peripheral nerve injury, and that this increase will lead to an enhanced functional recovery. The lateral gastrocnemius (<jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content>) muscle of adult female Lewis rats was injected unilaterally with <jats:styled-content style=\"fixed-case\">AAV<\/jats:styled-content>9\u2010 hsyn\u2010 <jats:styled-content style=\"fixed-case\">hM<\/jats:styled-content>3Dq\u2010<jats:styled-content style=\"fixed-case\">mC<\/jats:styled-content>herry (7.6\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup> viral genomes\/\u03bcL) to transduce Gq\u2010<jats:styled-content style=\"fixed-case\">DREADD<\/jats:styled-content> expression in <jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> neurons. The contralateral <jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> muscle served as an uninjected control. No significant changes in either spontaneous <jats:styled-content style=\"fixed-case\">EMG<\/jats:styled-content> activity or electrically evoked direct muscle (M) responses were found in either muscle after injection of <jats:styled-content style=\"fixed-case\">CNO<\/jats:styled-content> (1\u00a0mg\/kg, i.p.). The amplitude of monosynaptic H\u2010reflexes in <jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> was increased after <jats:styled-content style=\"fixed-case\">CNO<\/jats:styled-content> treatment exclusively in muscles previously injected with virus, suggesting that Gq\u2010<jats:styled-content style=\"fixed-case\">DREADD<\/jats:styled-content> activation increased neuronal excitability. After bilateral sciatic nerve transection and repair, additional rats were treated similarly with <jats:styled-content style=\"fixed-case\">CNO<\/jats:styled-content> for up to three days after injury. Electrophysiological data were collected at 2, 4 and 6\u00a0weeks after injury. Evoked <jats:styled-content style=\"fixed-case\">EMG<\/jats:styled-content> responses were observed as early as 2\u00a0weeks after injury only in Gq\u2010<jats:styled-content style=\"fixed-case\">DREADD<\/jats:styled-content> expressing virus injected <jats:styled-content style=\"fixed-case\">LG<\/jats:styled-content> muscle. By 4\u00a0weeks after injury, both M\u2010response and H\u2010reflex amplitudes were significantly greater in muscles previously injected with viral vector than contralateral, uninjected muscles. Increases in the excitability of injured neurons produced by this novel use of Gq\u2010<jats:styled-content style=\"fixed-case\">DREADD<\/jats:styled-content> were sufficient to promote an enhancement in functional recovery after a sciatic nerve injury.<\/jats:p>","DOI":"10.1111\/ejn.13550","type":"journal-article","created":{"date-parts":[[2017,2,28]],"date-time":"2017-02-28T09:37:22Z","timestamp":1488274642000},"page":"1252-1257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Chemogenetic enhancement of functional recovery after a sciatic nerve injury"],"prefix":"10.1111","volume":"45","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 Emory University 615 Michael St Atlanta GA 30322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur W.","family":"English","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Emory University 615 Michael St Atlanta GA 30322 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.06.014"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02602.2000"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700293104"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-196345060-00006"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00946.2012"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00129.2016"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2013.189"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20678"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20339"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2011.02.013"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5167-13.2014"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-015-0415-1"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13005"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1179\/174313208X362488"},{"key":"e_1_2_11_16_1","unstructured":"Jaiswal P.B.&English A.W.(2015)Pharmacogenetic enhancement of functional recovery from sciatic nerve transection. 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