{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T18:29:25Z","timestamp":1787077765763,"version":"build-2736575974"},"reference-count":67,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2024ZZ2039"],"award-info":[{"award-number":["2024ZZ2039"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31871085"],"award-info":[{"award-number":["31871085"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007219","name":"STCSM | Natural Science Foundation of Shanghai Municipality","doi-asserted-by":"publisher","award":["21ZR1407300"],"award-info":[{"award-number":["21ZR1407300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,25]]},"abstract":"<jats:p>\n                    Slow nasal breathing alleviates negative moods, but the precise nose-to-limbic pathways and their causal contributions remain unclear. Here, we identify a pathway in mice from olfactory sensory neurons (OSNs) in the nasal cavity to mitral cells in the olfactory bulb (OB), then to parvalbumin-positive (PV\n                    <jats:sup>+<\/jats:sup>\n                    ) long-projecting interneurons in the perirhinal cortex (PRC), and subsequently to glutamatergic neurons in the posterior basolateral amygdala (pBLA), through which nasal afferent activity bidirectionally regulates anxiety in a frequency-dependent manner. Low-frequency nasal airflow or optogenetic OSN stimulation induced anxiolysis and increased PRC high-gamma power by activating PV\n                    <jats:sup>+<\/jats:sup>\n                    neurons, whereas high-frequency had opposite effects. Chemogenetic silencing of the OB\n                    <jats:bold>\u2192<\/jats:bold>\n                    PRC\n                    <jats:sup>PV<\/jats:sup>\n                    pathway eliminated the frequency-dependent regulation of anxiety-like behaviors driven by OSN stimulation. Selective activation or inhibition of the identified circuit generated opposing behavioral effects (anxiolytic vs. anxiogenic, respectively), paralleling the results of low- and high-frequency OSN stimulations. Strikingly, a 2-wk low-frequency nasal airflow\/optogenetic OSN stimulation regimen ameliorated anxiety-like behaviors and restored PRC high-gamma activity in an anxiety model. This study reveals a nose\u2013brain axis bidirectionally modulating anxiety via nasal afferent frequency, providing potential interventional strategies and targets for anxiety disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2603853123","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:59:27Z","timestamp":1787075967000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A nose-to-brain circuit underlies anxiety regulation by nasal afferent frequency in mice"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0175-1539","authenticated-orcid":false,"given":"Xinsong","family":"Guo","sequence":"first","affiliation":[{"name":"Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Brain Function and Disorders, Ministry of Education Frontiers Center for Brain Science, Institutes of Brain Science, Fudan 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