{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:17Z","timestamp":1785416477545,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,20]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"crossref","award":["T32MH019113"],"award-info":[{"award-number":["T32MH019113"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000025","name":"NIMH","doi-asserted-by":"crossref","award":["R01MH113325"],"award-info":[{"award-number":["R01MH113325"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIDA","award":["R01DA052953"],"award-info":[{"award-number":["R01DA052953"]}]},{"name":"NIDA","award":["R01DA037216"],"award-info":[{"award-number":["R01DA037216"]}]},{"name":"VA","award":["IK2BX006118"],"award-info":[{"award-number":["IK2BX006118"]}]},{"name":"VA","award":["IO1BX004440"],"award-info":[{"award-number":["IO1BX004440"]}]},{"name":"The Juanita Bartlett Professorship"},{"id":[{"id":"https:\/\/ror.org\/01ah2ch91","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Responding appropriately to threats is critical for survival. Dysregulated defensive responses are core features of psychiatric illnesses including panic disorder and post-traumatic stress disorder. Carbon dioxide (CO\n                    <jats:sub>2<\/jats:sub>\n                    ) inhalation evokes defensive behaviors in both humans and mice. Here we investigated the role of acid-sensing ion channels (ASICs) in CO\n                    <jats:sub>2<\/jats:sub>\n                    -evoked jumping in mice.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Defensive behaviors (jumping and freezing) were assessed in response to CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation and basolateral amygdala (BLA) acidification. We tested the role of ASICs using global knockout mice and\n                    <jats:italic>\n                      Asic1a\n                      <jats:sup>loxP\/loxP<\/jats:sup>\n                    <\/jats:italic>\n                    mice transduced with AAV-CMV-Cre or AAV-CaMKII-Cre in the BLA. Effects of CO\n                    <jats:sub>2<\/jats:sub>\n                    on single neuron firing and local field potentials were studied via BLA microwire arrays.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    ASIC1A disruption increased CO\n                    <jats:sub>2<\/jats:sub>\n                    -evoked jumping while reducing freezing, paralleled by increased BLA c-Fos induction. Acidification of the BLA recapitulated these effects. Virus-mediated ASIC1A disruption in BLA did not resolve the locus of ASIC1A action in jumping. CO\n                    <jats:sub>2<\/jats:sub>\n                    inhalation suppressed firing in most BLA neurons, though a small number increased firing. ASIC1A disruption enhanced CO\n                    <jats:sub>2<\/jats:sub>\n                    -induced suppression of narrow waveform neurons (putative interneurons), and facilitated excitation of wide waveform neurons (putative principal neurons). Additionally, CO\n                    <jats:sub>2<\/jats:sub>\n                    produced concentration-dependent broadband power suppression with selective theta enhancement, effects that were augmented by ASIC1A disruption.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, these findings suggest that ASIC1A promotes interneuron activity during acidosis and that its loss may reduce inhibition of principal neuron output, shifting defensive responses from freezing toward jumping. These results advance our understanding of how brain pH and ASICs regulate defensive behavior, with potential implications for understanding dysregulated defensive responses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.18.725939","type":"posted-content","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:55:18Z","timestamp":1779310518000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of ASIC1A-dependent inhibitory neuron activity in basolateral amygdala is associated with increased CO\n                  <sub>2<\/sub>\n                  -evoked jumping"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6710-984X","authenticated-orcid":false,"given":"Rebecca J","family":"Taugher-Hebl","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Iowa, Iowa City, IA, USA"},{"name":"Department of Veterans Affairs Medical Center, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey C","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Iowa, Iowa City, IA, USA"},{"name":"Department of Veterans Affairs Medical Center, Iowa City, IA, USA"},{"name":"Department of Internal Medicine, University of Iowa, Iowa City, IA, USA"},{"name":"Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA"},{"name":"Iowa Neuroscience Institute, University of Iowa, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin J","family":"Kreple","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Ghobbeh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Iowa, Iowa City, IA, USA"},{"name":"Department of Veterans Affairs Medical Center, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Z","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Iowa, Iowa City, IA, USA"},{"name":"Department of Veterans Affairs Medical Center, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0196-5480","authenticated-orcid":false,"given":"Gail I S","family":"Harmata","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Iowa, Iowa City, IA, USA"},{"name":"Iowa Neuroscience Institute, University of Iowa, Iowa City, IA"},{"name":"Department of Radiology, University of Iowa, Iowa City, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie M","family":"Conlon","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Neuroscience, University 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