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To address this question, we used an optogenetic approach to selectively activate the subset of VMN neurons that express neuronal nitric oxide synthase 1 (VMNNOS1 neurons) implicated in glucose counterregulation. We found that photoactivation of these neurons elicits 1) robust hyperglycemia achieved by activation of counterregulatory responses usually reserved for the physiological response to hypoglycemia and 2) defensive immobility behavior. Moreover, we show that the glucagon, but not corticosterone, response to insulin-induced hypoglycemia is blunted by photoinhibition of the same neurons. To investigate the neurocircuitry by which VMNNOS1 neurons mediate these effects, and to determine whether these diverse effects are dissociable from one another, we activated downstream VMNNOS1 projections in either the anterior bed nucleus of the stria terminalis (aBNST) or the periaqueductal gray (PAG). Whereas glycemic responses are fully recapitulated by activation of VMNNOS1 projections to the aBNST, freezing immobility occurred only upon activation of VMNNOS1 terminals in the PAG. These findings support previous evidence of a VMN\u2192aBNST neurocircuit involved in glucose counterregulation and demonstrate that activation of VMNNOS1 neuronal projections supplying the PAG robustly elicits defensive behaviors.<\/jats:p>","DOI":"10.2337\/db18-0380","type":"journal-article","created":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T15:15:27Z","timestamp":1537974927000},"page":"2518-2529","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":53,"title":["Distinct Neuronal Projections From the Hypothalamic Ventromedial Nucleus Mediate Glycemic and Behavioral Effects"],"prefix":"10.2337","volume":"67","author":[{"given":"Chelsea L.","family":"Faber","sequence":"first","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miles E.","family":"Matsen","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin R.","family":"Velasco","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Damian","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao Anh","family":"Phan","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Adam","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University, Omaha, NE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Therattil","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael W.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-8386","authenticated-orcid":false,"given":"Gregory J.","family":"Morton","sequence":"additional","affiliation":[{"name":"UW Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"2022031303514055500_B1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1126\/science.6264602","article-title":"Glucoreceptors controlling feeding and blood glucose: location in the hindbrain","volume":"213","author":"Ritter","year":"1981","journal-title":"Science"},{"key":"2022031303514055500_B2","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.2337\/db07-1528","article-title":"The locus for hypoglycemic detection shifts with the rate of fall in glycemia: the role of portal-superior mesenteric vein glucose sensing","volume":"57","author":"Saberi","year":"2008","journal-title":"Diabetes"},{"key":"2022031303514055500_B3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1210\/TEAM.9781936704200.ch2","article-title":"2. 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