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Adv."],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>Cochlear damage triggers compensatory primary auditory cortex (A1) plasticity that amplifies responses to residual sensory inputs, thereby contributing to the restoration of both cortical responsiveness to sound and perceptual sound detection threshold. However, this adaptation can become maladaptive, producing neuronal hyperactivity that contributes to tinnitus and hyperacusis. The neuromodulatory mechanisms governing these adaptive and maladaptive changes remain unknown. Here, we demonstrate that noise-induced cochlear injury triggers bidirectional synaptic zinc signaling plasticity that potentiates activity in excitatory principal neurons and parvalbumin-expressing interneurons, while suppressing activity in somatostatin-expressing interneurons. These cell-type-specific effects of synaptic zinc plasticity contribute to restoring A1 responsiveness to sound and perceptual detection thresholds, while being necessary for neural hyperactivity. Together, our findings establish synaptic zinc as a pivotal neuromodulator that shapes both adaptive and maladaptive cortical plasticity and identify a promising therapeutic target for improving perceptual recovery after cochlear damage and mitigating tinnitus and hyperacusis.<\/jats:p>","DOI":"10.1126\/sciadv.aee9298","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:01:07Z","timestamp":1786557667000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Synaptic zinc plasticity shapes adaptive and maladaptive cortical plasticity following cochlear injury"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5139-1425","authenticated-orcid":true,"given":"Manoj","family":"Kumar","sequence":"first","affiliation":[{"name":"Pittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15261."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Linnertz","sequence":"additional","affiliation":[{"name":"Pittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15261."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Bizup","sequence":"additional","affiliation":[{"name":"Pittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15261."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5948-5618","authenticated-orcid":true,"given":"Wenyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwang","family":"Ai","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4583-145X","authenticated-orcid":true,"given":"Thanos","family":"Tzounopoulos","sequence":"additional","affiliation":[{"name":"Pittsburgh Hearing Research Center, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15261."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgh-2022-010501"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2015.11.004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2018.01.008"},{"key":"e_1_3_2_5_2","first-page":"233121652311564","article-title":"Plasticity after hearing rehabilitation in the aging brain","volume":"27","author":"Lazard D. 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