{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:18:36Z","timestamp":1775063916597,"version":"3.50.1"},"reference-count":53,"publisher":"American Physiological Society","issue":"1","funder":[{"DOI":"10.13039\/100000006","name":"DOD | Office of Naval Research (ONR)","doi-asserted-by":"publisher","award":["MURI: N000141612829"],"award-info":[{"award-number":["MURI: N000141612829"]}],"id":[{"id":"10.13039\/100000006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL116845"],"award-info":[{"award-number":["HL116845"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["RO1 HL085188"],"award-info":[{"award-number":["RO1 HL085188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["K24 HL132105"],"award-info":[{"award-number":["K24 HL132105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["RO1 HL081823"],"award-info":[{"award-number":["RO1 HL081823"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["T32 HL134632"],"award-info":[{"award-number":["T32 HL134632"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["RO1 HL081823"],"award-info":[{"award-number":["RO1 HL081823"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:p>In patients with obstructive sleep apnea (OSA), the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Experimental studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contributes to depression of hypoglossal motoneurons and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. In this new study, we developed a biophysical network model to test the hypothesis that, to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons needs to include excitatory and inhibitory perihypoglossal interneurons that mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. In the model, the state-dependent activation of the hypoglossal motoneurons was in qualitative agreement with in vivo data during simulated rapid eye movement (REM) and non-REM sleep. The model was applied to test the mechanisms of action of noradrenergic and serotonergic drugs during REM sleep as observed in vivo. We conclude that the proposed minimal neuronal circuit is sufficient to explain in vivo data and supports the hypothesis that perihypoglossal interneurons may mediate state-dependent monoaminergic drive to hypoglossal motoneurons. The population of the hypothesized perihypoglossal interneurons may serve as novel targets for pharmacological treatment of OSA.<\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY In vivo studies suggest that during rapid eye movement sleep, withdrawal of noradrenergic and serotonergic drives critically contributes to depression of hypoglossal motoneurons (HMs), which innervate the tongue muscles. By means of a biophysical model, which is consistent with a broad range of empirical data, we demonstrate that the neuronal network controlling the excitability of HMs needs to include excitatory and inhibitory interneurons that mediate noradrenergic and serotonergic drives to HMs.<\/jats:p>","DOI":"10.1152\/jn.00728.2017","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T16:31:29Z","timestamp":1522859489000},"page":"296-305","source":"Crossref","is-referenced-by-count":7,"title":["Computational model of brain-stem circuit for state-dependent control of hypoglossal motoneurons"],"prefix":"10.1152","volume":"120","author":[{"given":"Mohsen","family":"Naji","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Komarov","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giri P.","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atul","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank L.","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"Rukhadze","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California"},{"name":"Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor B.","family":"Fenik","sequence":"additional","affiliation":[{"name":"Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California"},{"name":"WebSciences International, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Bazhenov","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Pulmonary, Critical Care &amp; Sleep Medicine, University of California, San Diego, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2016.05.036"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-19-08691.2002"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.6.3758"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200605-597OC"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nn0602-857"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(79)90326-1"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-008-0132-4"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1162\/neco.1994.6.1.14"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00344-X"},{"key":"B10","volume-title":"Methods in Neuronal Modeling","author":"Destexhe A","year":"1998"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-2292"},{"key":"B12","first-page":"S37","volume":"22","author":"Fenik V","year":"1999","journal-title":"Sleep"},{"key":"B13","first-page":"237","volume":"142","author":"Fenik V","year":"2004","journal-title":"Arch Ital Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00254"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.2005.00461.x"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200412-1750OC"},{"key":"B17","first-page":"815.21","volume-title":"Soc Neurosci Abstr A","author":"Fenik VB","year":"2015"},{"key":"B18","first-page":"A47","volume-title":"Sleep (Basel)","volume":"2016","author":"Fenik VB","year":"2016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/srep44392"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.4340"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1654OC"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90743-0"},{"key":"B23","first-page":"719","volume":"72","author":"Horner RL","year":"1989","journal-title":"Q J Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/srep45860"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60734-5"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-04-01548.2003"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-016-0622-8"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00460.2014"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90517-Q"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90563-M"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-18-07384.2001"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/31.11.1471"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/382363a0"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1314084"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115751"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.052357"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.74.5.1911"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.89.4.1275"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00703.2004"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1978.44.6.931"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.5.858"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.11.013"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1995.73.5.1799"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00423.2013"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.5.R1776"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200502-258OC"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.12.040"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1308659"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/137.4.889"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(82)91130-7"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63488-7.00004-5"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)90157-4"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00355-3"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00728.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T02:37:04Z","timestamp":1569033424000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00728.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,7,1]]}},"alternative-id":["10.1152\/jn.00728.2017"],"URL":"https:\/\/doi.org\/10.1152\/jn.00728.2017","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/199117","asserted-by":"object"}]},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"value":"0022-3077","type":"print"},{"value":"1522-1598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,1]]}}}