{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T05:46:36Z","timestamp":1775454396326,"version":"3.50.1"},"reference-count":84,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK137224"],"award-info":[{"award-number":["DK137224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK122842"],"award-info":[{"award-number":["DK122842"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Presympathetic neurons in the ventrolateral and ventromedial medulla (VLM\/VMM) control sympathetic tone, and GABA and glycine were identified as inhibitory neurotransmitters. Although glycinergic inhibition of presympathetic neurons in the VLM\/VMM has been shown, the sources of glycinergic inputs and the mechanism of glycine release are ill\u2010defined. Here, we tested whether presympathetic neurons in the VLM\/VMM receive glycinergic inputs. Glycine is recycled by glycine transporter 2 (GlyT\n                      <jats:sub>2<\/jats:sub>\n                      ), which is a reliable marker of glycinergic neurons. GlyT\n                      <jats:sub>2<\/jats:sub>\n                      <jats:sup>Cre<\/jats:sup>\n                      mice were cross bred with channelrhodopsin (ChR2) mice to generate GlyT\n                      <jats:sub>2<\/jats:sub>\n                      <jats:sup>ChR2\/EYFP<\/jats:sup>\n                      mice to be able to selectively stimulate GlyT2\u2010expressing fibres. Presympathetic neurons in the VLM\/VMM were retrogradely labelled with pseudorabies virus and whole\u2010cell, patch clamp recordings were conducted in brainstem slices. Our study demonstrates that inhibitory synaptic currents recorded from presympathetic VLM\/VMM neurons are mediated by GABA and glycine. We found that increasing the activity of inhibitory synapses facilitates glycine release. Light stimulation of GlyT\n                      <jats:sub>2<\/jats:sub>\n                      <jats:sup>ChR2\/EYFP<\/jats:sup>\n                      fibres triggered monosynaptic evoked currents composed of GABA and glycine and we found that sustained glycine release depends on glycine uptake mediated by GlyT\n                      <jats:sub>2<\/jats:sub>\n                      . In addition, we used a combination of monosynaptic and transsynaptic viral tracings to identify the location of presympathetic glycinergic neurons in the ventral brainstem, and immunostaining to reveal the expression of GlyR \u03b11, \u03b13 and \u03b2 subunits in VLM\/VMM neurons. Our study identified that GlyT2\u2010expressing neurons rely on release of both GABA and glycine to generate inhibitory currents. However, the potential role and the necessity for both neurotransmitters in the control of presympathetic VLM\/VMM neurons require additional studies.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70390-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Presympathetic neurons in the mouse ventrolateral\/ventromedial medulla (VLM\/VMM) receive monosynaptic glycinergic inputs that release both GABA and glycine.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Glycinergic neurons were identified in the lateral paragigantocellular nucleus and B\u00f6tzinger complex.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increasing the activity of inhibitory synapses facilitates glycine release and sustained glycine release depends on glycine uptake mediated by glycine transporter 2 (GlyT2).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Three prevalent forms of glycine receptors (\u03b11, \u03b13 and \u03b2) are expressed in the VLM\/VMM.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our study demonstrates the necessity of GABA and glycine for the regulation of presympathetic neurons and thus highlights the need for a better understanding of glycinergic circuits.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp288116","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T15:49:34Z","timestamp":1771602574000},"page":"2939-2957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The sympathoregulatory region of the mouse rostral brainstem relies on both GABA and glycine to generate inhibitory currents"],"prefix":"10.1113","volume":"604","author":[{"given":"Hong","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie D.","family":"Desmoulins","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrien J. R.","family":"Molinas","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney M.","family":"Dugas","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1412-0041","authenticated-orcid":false,"given":"Andrea","family":"Zsombok","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"},{"name":"Brain Institute Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2320-7632","authenticated-orcid":false,"given":"Andrei V.","family":"Derbenev","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine Tulane University  New Orleans LA USA"},{"name":"Brain Institute Tulane University  New Orleans LA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90503-7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00164791"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2018.00040"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1024-07.2007"},{"key":"e_1_2_5_6_1","first-page":"H686","article-title":"Depressor neurons in rabbit caudal medulla act via GABA receptors in rostral medulla","volume":"254","author":"Blessing W. W.","year":"1988","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00325.2016"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(80)90112-4"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90267-4"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2024.103976"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90308-A"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.2.323"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01070.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-023-01033-x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2017.00009"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.067470"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.77.1.229"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.5.2213"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017532"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013466"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001127)427:4<634::AID-CNE10>3.0.CO;2-X"},{"key":"e_1_2_5_22_1","volume-title":"The mouse brain in stereotaxic coordinates","author":"Franklin K.","year":"2007"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00511.2009"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00155.2013"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0820"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1706-17.2017"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP276467"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00673-1"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.028"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1902"},{"key":"e_1_2_5_31_1","first-page":"R1063","article-title":"Rostral ventrolateral medulla and sympathorespiratory integration in rats","volume":"259","author":"Guyenet P. G.","year":"1990","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094925"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01238-9"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.09.090"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00517"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020911-153315"},{"key":"e_1_2_5_37_1","first-page":"65","article-title":"A simple sequentially rejective multiple test procedure","volume":"6","author":"Holm S.","year":"1979","journal-title":"Scandinavian Journal of Statistics"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035293"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.250647"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10310.1998"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00013.2013"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/325529a0"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5375.419"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-4-00001.x"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0103-09.2009"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07434.1999"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)41598-0"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00415-8"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.010"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2003"},{"key":"e_1_2_5_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.07.034"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00249.2016"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90145-0"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1125-17.2017"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3040-09.2010"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2474-7"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0719-14.2014"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-19-0312"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.87.5.2624"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020682"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07709"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.22.7224"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1814"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005702"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0509-08.2008"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.016063"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.23.633"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990517)407:4<583::AID-CNE8>3.0.CO;2-E"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00221.x"},{"key":"e_1_2_5_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1997.77.4.1853"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702041104"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20332"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-07-02139.1990"},{"key":"e_1_2_5_74_1","first-page":"R672","article-title":"GABA\u2010mediated baroreceptor inhibition of reticulospinal neurons","volume":"249","author":"Sun M. K.","year":"1985","journal-title":"American Journal of Physiology"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.188292"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1977.sp011725"},{"key":"e_1_2_5_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2014.04.010"},{"key":"e_1_2_5_78_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284589"},{"key":"e_1_2_5_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.04.016"},{"key":"e_1_2_5_80_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2541-12.2013"},{"key":"e_1_2_5_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.09.009"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06812-z"},{"key":"e_1_2_5_83_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03952.1995"},{"key":"e_1_2_5_84_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2023"},{"key":"e_1_2_5_85_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.64.092501.114547"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/JP288116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:43:26Z","timestamp":1775450606000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP288116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,20]]},"references-count":84,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1113\/JP288116"],"URL":"https:\/\/doi.org\/10.1113\/jp288116","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,20]]},"assertion":[{"value":"2024-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}