{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:06:44Z","timestamp":1786550804206,"version":"build-2736575974"},"reference-count":52,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health (NIMH)","doi-asserted-by":"crossref","award":["R01-MH093362"],"award-info":[{"award-number":["R01-MH093362"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health (NIMH)","doi-asserted-by":"crossref","award":["R21MH083213"],"award-info":[{"award-number":["R21MH083213"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological Psychiatry"],"published-print":{"date-parts":[[2016,10]]},"DOI":"10.1016\/j.biopsych.2016.04.022","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T18:14:58Z","timestamp":1463076898000},"page":"541-551","source":"Crossref","is-referenced-by-count":76,"title":["Microglial Acid Sensing Regulates Carbon Dioxide-Evoked Fear"],"prefix":"10.1016","volume":"80","author":[{"given":"Lauren Larke","family":"Vollmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriparna","family":"Ghosal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Ahlbrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Santin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Ratliff-Rang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis G.A.","family":"Patrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Rush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian P.","family":"Lewkowich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Herman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Putnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Sah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopsych.2016.04.022_bib1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cell.2011.10.009","article-title":"Molecular mechanisms of fear learning and memory","volume":"147","author":"Johansen","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.biopsych.2016.04.022_bib2","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.neubiorev.2011.12.014","article-title":"Neural and cellular mechanisms of fear and extinction memory formation","volume":"36","author":"Orsini","year":"2012","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.biopsych.2016.04.022_bib3","doi-asserted-by":"crossref","first-page":"5627","DOI":"10.2174\/138161212803530745","article-title":"On the psychotropic effects of carbon dioxide","volume":"18","author":"Colasanti","year":"2012","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.biopsych.2016.04.022_bib4","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1176\/ajp.150.8.1149","article-title":"Carbon dioxide hypersensitivity, hyperventilation, and panic disorder","volume":"150","author":"Papp","year":"1993","journal-title":"Am J Psychiatry"},{"key":"10.1016\/j.biopsych.2016.04.022_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0887-6185(02)00181-0","article-title":"Carbon dioxide in the study of panic disorder: Issues of definition, methodology, and outcome","volume":"17","author":"Rassovsky","year":"2003","journal-title":"J Anxiety Disord"},{"key":"10.1016\/j.biopsych.2016.04.022_bib6","doi-asserted-by":"crossref","first-page":"8270","DOI":"10.1073\/pnas.1205902109","article-title":"Detecting activity-evoked pH changes in human brain","volume":"109","author":"Magnotta","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2016.04.022_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1982.sp014397","article-title":"Central chemosensitivity and the reaction theory","volume":"332","author":"Loeschcke","year":"1982","journal-title":"J Physiol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib8","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cell.2009.10.029","article-title":"The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior","volume":"139","author":"Ziemann","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.biopsych.2016.04.022_bib9","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nn.3323","article-title":"Fear and panic in humans with bilateral amygdala damage","volume":"16","author":"Feinstein","year":"2013","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib10","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/nn1997","article-title":"Microglia: active sensor and versatile effector cells in the normal and pathologic brain","volume":"10","author":"Hanisch","year":"2007","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2013.12.010","article-title":"Dynamic structural remodelling of microglia in health and disease: A review of the models, the signals and the mechanisms","volume":"37","author":"Walker","year":"2014","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.biopsych.2016.04.022_bib12","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0166-2236(96)10049-7","article-title":"Microglia: a sensor for pathological events in the CNS","volume":"19","author":"Kreutzberg","year":"1996","journal-title":"Trends Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib13","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1152\/physrev.00011.2010","article-title":"Physiology of microglia","volume":"91","author":"Kettenmann","year":"2011","journal-title":"Physiol Rev"},{"key":"10.1016\/j.biopsych.2016.04.022_bib14","doi-asserted-by":"crossref","first-page":"7220","DOI":"10.1523\/JNEUROSCI.20-19-07220.2000","article-title":"Potentiation of a voltage-gated proton current in acidosis-induced swelling of rat microglia","volume":"20","author":"Morihata","year":"2000","journal-title":"J Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0006-8993(99)02221-0","article-title":"Extracellular acidification decreases the basal motility of cultured mouse microglia via the rearrangement of the actin cytoskeleton","volume":"853","author":"Faff","year":"2000","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2016.04.022_bib16","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.bbrc.2009.05.133","article-title":"Acid-sensing by the T cell death-associated gene 8 (TDAG8) receptor cloned from rat brain","volume":"386","author":"McGuire","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.biopsych.2016.04.022_bib17","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1073\/pnas.0409415102","article-title":"Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells","volume":"102","author":"Radu","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2016.04.022_bib18","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1096\/fasebj.7.8.8500693","article-title":"Sensory circumventricular organs and brain homeostatic pathways","volume":"7","author":"Johnson","year":"1993","journal-title":"FASEB J"},{"key":"10.1016\/j.biopsych.2016.04.022_bib19","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.pnpbp.2013.02.014","article-title":"Angiotensin II\u2019s role in sodium lactate-induced panic-like responses in rats with repeated urocortin 1 injections into the basolateral amygdala: amygdala angiotensin receptors and panic","volume":"44","author":"Johnson","year":"2013","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2016.04.022_bib20","doi-asserted-by":"crossref","first-page":"9726","DOI":"10.1523\/JNEUROSCI.17-24-09726.1997","article-title":"The circumventricular organs form a potential neural pathway for lactate sensitivity: implications for panic disorder","volume":"17","author":"Shekhar","year":"1997","journal-title":"J Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib21","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1749-6632.1999.tb09315.x","article-title":"Role of the basolateral amygdala in panic disorder","volume":"877","author":"Shekhar","year":"1999","journal-title":"Ann N Y Acad Sci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib22","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1128\/MCB.26.2.668-677.2006","article-title":"Normal immune development and glucocorticoid-induced thymocyte apoptosis in mice deficient for the T-cell death-associated gene 8 receptor","volume":"26","author":"Radu","year":"2006","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.biopsycho.2013.06.004","article-title":"Carbon dioxide inhalation as a human experimental model of panic: The relationship between emotions and cardiovascular physiology","volume":"94","author":"Leibold","year":"2013","journal-title":"Biol Psychol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib24","doi-asserted-by":"crossref","first-page":"20529","DOI":"10.1073\/pnas.1007740107","article-title":"Pleasurable behaviors reduce stress via brain reward pathways","volume":"107","author":"Ulrich-Lai","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2016.04.022_bib25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.resp.2013.09.001","article-title":"Cardiorespiratory effects of gap junction blockade in the locus coeruleus in unanesthetized adult rats","volume":"190","author":"Patrone","year":"2014","journal-title":"Respir Physiol Neurobiol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib26","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1161\/STROKEAHA.109.564146","article-title":"Anxiety after cardiac arrest\/cardiopulmonary resuscitation: exacerbated by stress and prevented by minocycline","volume":"40","author":"Neigh","year":"2009","journal-title":"Stroke"},{"key":"10.1016\/j.biopsych.2016.04.022_bib27","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.psyneuen.2007.09.004","article-title":"A dual role for interleukin-1 in hippocampal-dependent memory processes","volume":"32","author":"Goshen","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.biopsych.2016.04.022_bib28","doi-asserted-by":"crossref","first-page":"16342","DOI":"10.1073\/pnas.1007583107","article-title":"Social interaction modulates autonomic, inflammatory, and depressive-like responses to cardiac arrest and cardiopulmonary resuscitation","volume":"107","author":"Norman","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2016.04.022_bib29","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1742-2094-10-4","article-title":"A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion","volume":"10","author":"Morrison","year":"2013","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.biopsych.2016.04.022_bib30","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1172\/JCI67569","article-title":"Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure","volume":"123","author":"Cutando","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1016\/j.biopsych.2016.04.022_bib31","doi-asserted-by":"crossref","first-page":"R780","DOI":"10.1152\/ajpregu.00029.2013","article-title":"Transient outwardly rectifying A currents are involved in the firing rate response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal rats","volume":"305","author":"Li","year":"2013","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib32","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1177\/0145445503256316","article-title":"The conditioning of dyspneic suffocation fear. Effects of carbon dioxide concentration on behavioral freezing and analgesia","volume":"27","author":"Mongeluzi","year":"2003","journal-title":"Behav Modif"},{"key":"10.1016\/j.biopsych.2016.04.022_bib33","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.physbeh.2015.03.012","article-title":"A potential role for the acid-sensing T cell death associated gene-8 (TDAG8) receptor in depression-like behavior","volume":"150","author":"Vollmer","year":"2015","journal-title":"Physiol Behav"},{"key":"10.1016\/j.biopsych.2016.04.022_bib34","article-title":"The sensory circumventricular organs of the mammalian brain","volume":"172","author":"McKinley","year":"2003","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib35","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.physbeh.2013.02.012","article-title":"Circumventricular organs: targets for integration of circulating fluid and energy balance signals?","volume":"121","author":"Mimee","year":"2013","journal-title":"Physiol Behav"},{"key":"10.1016\/j.biopsych.2016.04.022_bib36","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/nn1130","article-title":"Midbrain serotonergic neurons are central pH chemoreceptors","volume":"6","author":"Severson","year":"2003","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib37","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.resp.2004.07.005","article-title":"CO2 central chemosensitivity: Why are there so many sensing molecules?","volume":"145","author":"Jiang","year":"2005","journal-title":"Respir Physiol Neurobiol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1176\/appi.ajp.2009.09030410","article-title":"Overgeneralization of conditioned fear as a pathogenic marker of panic disorder","volume":"167","author":"Lissek","year":"2010","journal-title":"Am J Psychiatry"},{"key":"10.1016\/j.biopsych.2016.04.022_bib39","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.autneu.2004.11.009","article-title":"Autonomic cardiovascular responses to hypercapnia in conscious rats: The roles of the chemo- and baroreceptors","volume":"117","author":"Oikawa","year":"2005","journal-title":"Auton Neurosci Basic Clin"},{"key":"10.1016\/j.biopsych.2016.04.022_bib40","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0034-5687(00)00161-4","article-title":"Multiple sites for central chemoreception: their roles in response sensitivity and in sleep and wakefulness","volume":"122","author":"Nattie","year":"2000","journal-title":"Respir Physiol"},{"key":"10.1016\/j.biopsych.2016.04.022_bib41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.brainres.2011.04.042","article-title":"Interaction between \u03b4 opioid receptors and benzodiazepines in CO2-induced respiratory responses in mice","volume":"1396","author":"Borkowski","year":"2011","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2016.04.022_bib42","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1161\/HYPERTENSIONAHA.113.01404","article-title":"Subfornical organ mediates sympathetic and hemodynamic responses to blood-borne proinflammatory cytokines","volume":"62","author":"Wei","year":"2013","journal-title":"Hypertension"},{"key":"10.1016\/j.biopsych.2016.04.022_bib43","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0006-8993(86)90799-7","article-title":"Neural projections subserving the initiation of a specific motivated behavior in the rat: new projections from the subfornical organ","volume":"379","author":"Swanson","year":"1986","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2016.04.022_bib44","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1111\/j.1460-9568.2009.07024.x","article-title":"Functional correlates of activity in neurons projecting from the lamina terminalis to the ventrolateral periaqueductal gray","volume":"30","author":"Uschakov","year":"2009","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.biopsych.2016.04.022_bib45","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/978-94-007-7359-2_14","article-title":"Carbonic anhydrases and brain pH in the control of neuronal excitability","volume":"75","author":"Ruusuvuori","year":"2014","journal-title":"Subcell Biochem"},{"key":"10.1016\/j.biopsych.2016.04.022_bib46","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1176\/ajp.2006.163.4.710","article-title":"Brain pH response to hyperventilation in panic disorder: Preliminary evidence for altered acid-base regulation","volume":"163","author":"Friedman","year":"2006","journal-title":"Am J Psychiatry"},{"key":"10.1016\/j.biopsych.2016.04.022_bib47","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1038\/tp.2015.67","article-title":"Acid-base dysregulation and chemosensory mechanisms in panic disorder: A translational update","volume":"5","author":"Vollmer","year":"2015","journal-title":"Transl Psychiatry"},{"key":"10.1016\/j.biopsych.2016.04.022_bib48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/sj.mp.4001224","article-title":"A chromosome 14 risk locus for simple phobia: Results from a genomewide linkage scan","volume":"8","author":"Gelernter","year":"2003","journal-title":"Mol Psychiatry"},{"issue":"pt 3","key":"10.1016\/j.biopsych.2016.04.022_bib49","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.neubiorev.2014.04.005","article-title":"Early-life risk factors for panic and separation anxiety disorder: Insights and outstanding questions arising from human and animal studies of CO2 sensitivity","volume":"46","author":"Battaglia","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"key":"10.1016\/j.biopsych.2016.04.022_bib50","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/da.21924","article-title":"Comorbidity and disease burden in the National Comorbidity Survey Replication (NCS-R)","volume":"29","author":"Gadermann","year":"2012","journal-title":"Depress Anxiety"},{"key":"10.1016\/j.biopsych.2016.04.022_bib51","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1002\/da.20564","article-title":"Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder","volume":"26","author":"Hoge","year":"2009","journal-title":"Depress Anxiety"},{"key":"10.1016\/j.biopsych.2016.04.022_bib52","doi-asserted-by":"crossref","first-page":"e249","DOI":"10.1038\/tp.2013.27","article-title":"Anxiety disorders and inflammation in a large adult cohort","volume":"3","author":"Vogelzangs","year":"2013","journal-title":"Transl Psychiatry"}],"container-title":["Biological Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006322316323782?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006322316323782?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T15:51:03Z","timestamp":1567871463000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006322316323782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["S0006322316323782"],"URL":"https:\/\/doi.org\/10.1016\/j.biopsych.2016.04.022","relation":{},"ISSN":["0006-3223"],"issn-type":[{"value":"0006-3223","type":"print"}],"subject":[],"published":{"date-parts":[[2016,10]]}}}