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To assess the effects of noise exposure on the hippocampus, guinea pigs were exposed to unilateral noise for 2 hr and 2 weeks later, immunohistochemistry was performed on hippocampal sections to examine vesicular acetylcholine transporter (VAChT) expression. To evaluate whether the changes in VAChT were relevant to tinnitus, another group of animals was exposed to the same noise band twice to induce tinnitus, which was assessed using gap\u2010prepulse Inhibition of the acoustic startle (GPIAS) 12\u2009weeks after the first noise exposure, followed by immunohistochemistry. Acoustic Brainstem Response (ABR) thresholds were elevated immediately after noise exposure for all experimental animals but returned to baseline levels several days after noise exposure. ABR wave I amplitude\u2010intensity functions did not show any changes after 2 or 12\u2009weeks of recovery compared to baseline levels. In animals assessed 2\u2010weeks following noise\u2010exposure, hippocampal VAChT puncta density decreased on both sides of the brain by 20\u201360% in exposed animals. By 12\u2009weeks following the initial noise exposure, changes in VAChT puncta density largely recovered to baseline levels in exposed animals that did not develop tinnitus, but remained diminished in animals that developed tinnitus. These tinnitus\u2010specific changes were particularly prominent in hippocampal synapse\u2010rich layers of the dentate gyrus and areas CA3 and CA1, and VAChT density in these regions negatively correlated with tinnitus severity. The robust changes in VAChT labeling in the hippocampus 2 weeks after noise exposure suggest involvement of this circuitry in auditory processing. After chronic tinnitus induction, tinnitus\u2010specific changes occurred in synapse\u2010rich layers of the hippocampus, suggesting that synaptic processing in the hippocampus may play an important role in the pathophysiology of tinnitus.<\/jats:p>","DOI":"10.1002\/hipo.23058","type":"journal-article","created":{"date-parts":[[2018,11,24]],"date-time":"2018-11-24T16:30:03Z","timestamp":1543077003000},"page":"669-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Remodeling of cholinergic input to the hippocampus after noise exposure and tinnitus induction in Guinea pigs"],"prefix":"10.1002","volume":"29","author":[{"given":"Liqin","family":"Zhang","sequence":"first","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"},{"name":"Molecular and Behavioral Neuroscience Institute University of Michigan Ann Arbor Michigan"},{"name":"Xiangya Medical School Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin","family":"Wu","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Martel","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"},{"name":"Department of Biomedical Engineering University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"West","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-6459","authenticated-orcid":false,"given":"Michael A.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"},{"name":"Molecular and Behavioral Neuroscience Institute University of Michigan Ann Arbor Michigan"},{"name":"Department of Molecular and Integrative Physiology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Shore","sequence":"additional","affiliation":[{"name":"Kresge Hearing Research Institute, Department of Otolaryngology University of Michigan Ann Arbor Michigan"},{"name":"Department of Biomedical Engineering University of Michigan Ann Arbor Michigan"},{"name":"Department of Molecular and Integrative Physiology University of Michigan Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,11]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","first-page":"1615","article-title":"Regulation of cognitive processing by hippocampal cholinergic tone","volume":"27","author":"Al\u2010Onaizi M. 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