{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:28:22Z","timestamp":1791487702033,"version":"4.3.4"},"reference-count":75,"publisher":"National Academy of Sciences","issue":"11","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS112255"],"award-info":[{"award-number":["R01NS112255"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS101105"],"award-info":[{"award-number":["R01NS101105"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS122961"],"award-info":[{"award-number":["R01NS122961"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"HHS | NIH | National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1TR001998"],"award-info":[{"award-number":["UL1TR001998"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["598928"],"award-info":[{"award-number":["598928"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["598741"],"award-info":[{"award-number":["598741"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TIRR Foundation","award":["0"],"award-info":[{"award-number":["0"]}]},{"name":"L.B. Research and Education Foundation","award":["0"],"award-info":[{"award-number":["0"]}]},{"DOI":"10.13039\/100010327","name":"Cincinnati Children's Research Foundation","doi-asserted-by":"publisher","award":["0"],"award-info":[{"award-number":["0"]}],"id":[{"id":"10.13039\/100010327","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,3,12]]},"abstract":"<jats:p>The specific roles that different types of neurons play in recovery from injury is poorly understood. Here, we show that increasing the excitability of ipsilaterally projecting, excitatory V2a neurons using designer receptors exclusively activated by designer drugs (DREADDs) restores rhythmic bursting activity to a previously paralyzed diaphragm within hours, days, or weeks following a C2 hemisection injury. Further, decreasing the excitability of V2a neurons impairs tonic diaphragm activity after injury as well as activation of inspiratory activity by chemosensory stimulation, but does not impact breathing at rest in healthy animals. By examining the patterns of muscle activity produced by modulating the excitability of V2a neurons, we provide evidence that V2a neurons supply tonic drive to phrenic circuits rather than increase rhythmic inspiratory drive at the level of the brainstem. Our results demonstrate that the V2a class of neurons contribute to recovery of respiratory function following injury. We propose that altering V2a excitability is a potential strategy to prevent respiratory motor failure and promote recovery of breathing following spinal cord injury.<\/jats:p>","DOI":"10.1073\/pnas.2313594121","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:46:23Z","timestamp":1709646383000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["V2a neurons restore diaphragm function in mice following spinal cord injury"],"prefix":"10.1073","volume":"121","author":[{"given":"Victoria N.","family":"Jensen","sequence":"first","affiliation":[{"name":"Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45219"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8766-2319","authenticated-orcid":false,"given":"Emily E.","family":"Huffman","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Kentucky College of Medicine, Lexington, KY 40536"},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3704-443X","authenticated-orcid":false,"given":"Frank L.","family":"Jalufka","sequence":"additional","affiliation":[{"name":"Department of Biology, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Walling","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45219"},{"name":"Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"C. Gibbs","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Texas A&amp;M University, College Station, TX 77843"},{"name":"Microscopy and Imaging Center, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan A.","family":"McCreedy","sequence":"additional","affiliation":[{"name":"Department of Biology, Texas A&amp;M University, College Station, TX 77843"},{"name":"Department of Biomedical Engineering, Texas A&amp;M University, College Station, TX 77843"},{"name":"Texas A&amp;M Institute for Neuroscience, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Alilain","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Kentucky College of Medicine, Lexington, KY 40536"},{"name":"Spinal Cord and Brain Injury Research Center, University of Kentucky College of Medicine, Lexington, KY 40536"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9644-2767","authenticated-orcid":false,"given":"Steven A.","family":"Crone","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"},{"name":"Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229"},{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2007.11753946"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.012616"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2017.1329076"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.05.025"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63488-7.00010-0"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.08.018"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2019.00084"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-819260-3.00014-7"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1195"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02243.x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1682"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.155425"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.01.016"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.04.003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2009.08.004"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2019.103305"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0595-z"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2019"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-083122-025325"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2023.1146449"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2007.0290"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05385-7"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00025"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.02.019"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.100"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01383.2007"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00589-2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.009"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.05.033"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0492-18.2019"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2017.5045"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2017.5439"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.208539"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2009.06.005"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00847.2002"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1895.sp000553"},{"key":"e_1_3_4_37_2","first-page":"289","article-title":"Ueber die Folgen einer halbseitigen Abstragung des Kopfmarkes","author":"Langendorff O.","year":"1887","unstructured":"O. Langendorff, Ueber die Folgen einer halbseitigen Abstragung des Kopfmarkes. Archiv. Fur. Physiol., 289\u2013295 (1887).","journal-title":"Archiv. Fur. Physiol."},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplegacy.1951.166.2.241"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1179\/016164105X21977"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00654.2016"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10199"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00690.2011"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.03.014"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06072.x"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.2007.11753947"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.07.002"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124803"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.10.018"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13021"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5231-12.2013"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.023"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.010"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2011.03.011"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.05.027"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.08.003"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.01.013"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00448.2016"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903020403"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902690104"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2018.09.005"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2011.07.004"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2010.08.026"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.06.004"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2009.06.014"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0445-12.2012"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3378-08.2008"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4849-09.2010"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4821-09.2010"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06937-0"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01395.2013"},{"key":"e_1_3_4_71_2","first-page":"208","volume-title":"V2a Neurons Pattern Respiratory Muscle Activity in Health and Disease","author":"Jensen V. N.","year":"2020","unstructured":"V. N. Jensen, V2a Neurons Pattern Respiratory Muscle Activity in Health and Disease (University of Cincinnati, 2020), p. 208."},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.22949"},{"key":"e_1_3_4_73_2","first-page":"684792","article-title":"Passive clearing and 3D lightsheet imaging of the intact and injured spinal cord in mice. Front. Cell","volume":"15","author":"McCreedy D. A.","year":"2021","unstructured":"D. A. McCreedy , Passive clearing and 3D lightsheet imaging of the intact and injured spinal cord in mice. Front. Cell. Neurosci. 15, 684792 (2021).","journal-title":"Neurosci"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.02.125"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.2344\/0003-3006(2006)53[53:FOEI]2.0.CO;2"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2313594121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T13:49:27Z","timestamp":1709646567000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2313594121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":75,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,3,12]]}},"alternative-id":["10.1073\/pnas.2313594121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2313594121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"assertion":[{"value":"2023-08-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2313594121"}}