{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:57:11Z","timestamp":1781110631565,"version":"3.54.1"},"reference-count":57,"publisher":"National Academy of Sciences","issue":"17","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271059 82071061"],"award-info":[{"award-number":["32271059 82071061"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["RO1DC0044050"],"award-info":[{"award-number":["RO1DC0044050"]}],"id":[{"id":"10.13039\/100000055","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":[[2026,4,28]]},"abstract":"<jats:p>\n                    Although dysregulated serotonergic neurotransmission has been implicated in the pathophysiology of tinnitus, the precise neural circuit mechanisms underlying this complex sensory neurological disorder remain elusive. In the current study, we investigated whether a serotonergic input from the dorsal raphe nucleus (DRN) to the dorsal cochlear nucleus (DCN), a key auditory brain region whose hyperactivity is associated with tinnitus, modulates behaviors in mice consistent with the presence of tinnitus. Using neural tracing and viral-genetic methods, we identified an anatomically and functionally defined serotonergic subpopulation in the DRN that projects to the DCN (5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    neurons). Optogenetic activation of 5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    circuit increased spike activity in DCN fusiform cells, exhibiting characteristics consistent with tinnitus-like electrical hyperactivity. Chemogenetic activation of 5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    circuit induced tinnitus-related behaviors in mice, which was largely reversed by blocking 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptors. Additionally, we found that noise exposure increased 5-HT levels in the DCN and the activity of 5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    neurons in mice with noise-induced tinnitus-related behaviors. Importantly, chemogenetic inhibition of 5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    circuit ameliorated significantly noise-induced tinnitus\u2013related behavior in mice. These results reveal that activation of 5-HT\n                    <jats:sup>DRN\u2192DCN<\/jats:sup>\n                    circuit induces hyperactivity in the DCN sufficient for the perceptual generation and modulation of tinnitus. These findings provide direct evidence that 5-HT neurons in the DRN play an important role in tinnitus and facilitate our understanding of the circuit mechanisms of pathophysiology in sensory neurological disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2509692123","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T19:01:46Z","timestamp":1776711706000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A discrete serotonergic circuit involved in the generation of tinnitus behavior"],"prefix":"10.1073","volume":"123","author":[{"given":"Meng-Ting","family":"Yu","sequence":"first","affiliation":[{"name":"School of Life Sciences and Medical Engineering, Anhui University","place":["Hefei, China"]},{"name":"Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University","place":["Hefei, 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University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3715-4794","authenticated-orcid":false,"given":"Jing-Wu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Heng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, University of Science and Technology of China","place":["Hefei, 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