{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:56:10Z","timestamp":1793645770060,"version":"4.5.1"},"posted":{"date-parts":[[2025,7,3]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DC008060"],"award-info":[{"award-number":["DC008060"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"David M. Rubenstein Fund for Hearing Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The parsing of sensory information into discrete topographic domains is a fundamental principle of sensory processing. In the auditory cortex, these domains evolve during a stimulus, with the onset and offset of tones evoking distinct spatial patterns of neural activity. However, it is not known where in the auditory system this spatial segregation occurs or how these dynamics are affected by hearing loss. Using widefield single photon neuronal Ca\n                  <jats:sup>2+<\/jats:sup>\n                  imaging in the inferior colliculus (IC) of awake mice, we found that pure tone stimuli elicited both spatially constrained neural activity within isofrequency bands and simultaneous sideband suppression. At cessation of the stimulus, offset responses emerged within the region of sideband suppression, demonstrating that simple stimuli elicit spatiotemporally distinct neural activity patterns to represent the presence of sound and sound termination. Because sound frequency is spatially encoded in the IC, this spatial shift creates a tonotopically distinct offset (tdOFF) response relative to sound onset. Two-photon Ca\n                  <jats:sup>2+<\/jats:sup>\n                  imaging confirmed that tdOFF neuron activity in the sideband region was suppressed during sound and elevated above baseline after stimulus termination, raising the possibility that rebound excitation could contribute to this post-stimulus activation. Loud noise exposure \u2013 a common model of hearing loss \u2013 abolished both sideband suppression and tdOFF responses. These results show that hearing loss profoundly reshapes the spatiotemporal pattern of sound processing by altering sideband activity. This preferential loss of sideband suppression and tdOFF activation after sound-induced injury in the auditory midbrain may contribute to hyperacusis and tinnitus by promoting neuronal hyperactivity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Sensory systems encode different features of stimuli by activating distinct neural networks.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Sound onsets and offsets elicit distinct neural patterns in the auditory cortex, although it is unclear where this separation originates or how it may change with hearing loss.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Using in vivo widefield Ca\n                        <jats:sup>2+<\/jats:sup>\n                        imaging in awake mice, we find that pure tone stimuli evoke spatiotemporally distinct on-and off patterns of neural activity in the auditory midbrain.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Neurons active during stimulus offset were suppressed by sound in sideband regions, raising the possibility that rebound excitation contributes to this post-stimulus activation.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Both sideband suppression and off responses were preferentially abolished following noise-induced hearing loss, raising the possibility that these changes may contribute to hearing loss-related syndromes such as tinnitus and hyperacusis.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.02.662630","type":"posted-content","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T23:05:19Z","timestamp":1751583919000},"source":"Crossref","is-referenced-by-count":1,"title":["Tonotopically distinct OFF responses arise in the mouse auditory midbrain following sideband suppression"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5217-107X","authenticated-orcid":false,"given":"Patrick D.","family":"Parker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M.","family":"Lauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-7378","authenticated-orcid":false,"given":"Dwight E.","family":"Bergles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025070708150490000_2025.07.02.662630v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13488"},{"key":"2025070708150490000_2025.07.02.662630v1.2","first-page":"011402","article-title":"Interpreting in vivo calcium signals from neuronal cell bodies, axons, and dendrites: a review","volume":"7","year":"2019","journal-title":"https:\/\/doi.org\/101117\/1NPh71011402"},{"key":"2025070708150490000_2025.07.02.662630v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1652-15.2016"},{"key":"2025070708150490000_2025.07.02.662630v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02088-w"},{"key":"2025070708150490000_2025.07.02.662630v1.5","first-page":"110898","article-title":"Central Gain Control in Tinnitus and Hyperacusis","volume":"5","year":"2014","journal-title":"Front Neurol"},{"key":"2025070708150490000_2025.07.02.662630v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-016-0001-8"},{"key":"2025070708150490000_2025.07.02.662630v1.7","doi-asserted-by":"crossref","unstructured":"Babola TA , Donovan N , Darcy SS , Spjut CD & Kanold PO (2025). 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