{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:29:30Z","timestamp":1789622970546,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,10,10]],"date-time":"2016-10-10T00:00:00Z","timestamp":1476057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008189","name":"Deafness Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008189","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Synaptic transmission at the endbulb of Held was assessed by whole\u2010cell patch clamp recordings from auditory neurons in mature (2\u20134\u00a0months) and aged (20\u201326\u00a0months) mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Synaptic transmission is degraded in aged mice, which may contribute to the decline in neural processing of the central auditory system during age\u2010related hearing loss.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The changes in synaptic transmission in aged mice can be partially rescued by improving calcium buffering, or decreasing action potential\u2010evoked calcium influx.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These experiments suggest potential mechanisms, such as regulating intraterminal calcium, that could be manipulated to improve the fidelity of transmission at the aged endbulb of Held.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Age\u2010related hearing loss (ARHL) is associated with changes to the auditory periphery that raise sensory thresholds and alter coding, and is accompanied by alterations in excitatory and inhibitory synaptic transmission, and intrinsic excitability in the circuits of the central auditory system. However, it remains unclear how synaptic transmission changes at the first central auditory synapses during ARHL. Using mature (2\u20134\u00a0months) and old (20\u201326\u00a0months) CBA\/CaJ mice, we studied synaptic transmission at the endbulb of Held. Mature and old mice showed no difference in either spontaneous quantal synaptic transmission or low frequency evoked synaptic transmission at the endbulb of Held. However, when challenged with sustained high frequency stimulation, synapses in old mice exhibited increased asynchronous transmitter release and reduced synchronous release. This suggests that the transmission of temporally precise information is degraded at the endbulb during ARHL. Increasing intraterminal calcium buffering with EGTA\u2010AM or decreasing calcium influx with \u03c9\u2010agatoxin IVA decreased the amount of asynchronous release and restored synchronous release in old mice. In addition, recovery from depression following high frequency trains was faster in old mice, but was restored to a normal time course by EGTA\u2010AM treatment. These results suggest that intraterminal calcium in old endbulbs may rise to abnormally high levels during high rates of auditory nerve firing, or that calcium\u2010dependent processes involved in release are altered with age. These observations suggest that ARHL is associated with a decrease in temporal precision of synaptic release at the first central auditory synapse, which may contribute to perceptual deficits in hearing.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272683","type":"journal-article","created":{"date-parts":[[2016,9,13]],"date-time":"2016-09-13T09:49:02Z","timestamp":1473760142000},"page":"919-934","source":"Crossref","is-referenced-by-count":43,"title":["Synaptic transmission at the endbulb of Held deteriorates during age\u2010related hearing loss"],"prefix":"10.1113","volume":"595","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-9805","authenticated-orcid":false,"given":"Ruili","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Neurosciences University of Toledo  Toledo OH 43614\u20102598 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Manis","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Surgery The University of North Carolina at Chapel Hill  Chapel Hill NC 27599\u20107545 USA"},{"name":"Department of Cell Biology and Physiology The University of North Carolina at Chapel Hill  Chapel Hill NC 27599\u20107070 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