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      Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline.

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          Abstract

          Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization.

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          Author and article information

          Journal
          J Neurosci
          The Journal of neuroscience : the official journal of the Society for Neuroscience
          Society for Neuroscience
          1529-2401
          0270-6474
          Aug 21 2013
          : 33
          : 34
          Affiliations
          [1 ] Department of Audiology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
          Article
          33/34/13686
          10.1523/JNEUROSCI.1783-13.2013
          3755715
          23966690
          474a3c22-0330-487d-bc7c-686ffc54c567
          History

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