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Featured ArticleBrief Communications

Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss

Stephen Paul Zachary and Paul Albert Fuchs
Journal of Neuroscience 1 July 2015, 35 (26) 9701-9706; https://doi.org/10.1523/JNEUROSCI.0879-15.2015
Stephen Paul Zachary
1Solomon H. Snyder Department of Neuroscience,
3Centers for Sensory Biology and
4Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, Maryland 21205
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Paul Albert Fuchs
1Solomon H. Snyder Department of Neuroscience,
2Department of Otolaryngology, and
3Centers for Sensory Biology and
4Hearing and Balance, Johns Hopkins School of Medicine, Baltimore, Maryland 21205
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    Figure 1.

    Efferent innervation returns to IHCs during ARHL. A, Examples of IHC membrane current responses evoked by 40 mm external K at P7–P10, 1 month, 8.5–9.5 months, and 11–12 months. Two synaptic events are marked with asterisks at 8.5 months. B, For the same ages, the proportion of apical IHCs with efferent activity in 40 mm K. C, Efferent release rates increase from 8.5–9.5 to 11–12 months of age. Data are means ± SEM of the first 10 release events across all recordings in 40 mm K. D, Hearing thresholds at 8 kHz were determined for 1-, 8.5- to 9.5-, and 11- to 12-month-old animals by ABR recordings. Means ± SEMs: 38.15 ± 3.29, 53.72 ± 4.58, and 91.14 ± 3.78. E, F, Ribbon and OHC survival at 8.5–9.5 and 11–12 months of age expressed as a percentage of each measurement at 1 month of age. Mean ± SEM ribbon values per IHC: 10.1 ± 0.22, 6.3 ± 0.36, and 4.5 ± 0.32. OHCs were quantified across a 200 μm distance in the same region. Mean ± SEM OHC values: 73 ± 1.15, 62.25 ± 1.03, and 55.33 ± 4.33. *p < 0.05, **p < 0.01, ***p < 0.001

  • Figure 2.
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    Figure 2.

    Efferents contacting aged IHCs are cholinergic and activate α9-containing receptors. A–D, Eleven- to 16-month-old IHCs, efferent transmitter release induced by 80 mm K, cells voltage clamped at −80 mV. A, Inward currents indicate that efferents contacting aged IHCs do not open Cl channels because those currents would be outward. ECl of −132 mV (n = 2 cells). B–D, Cells voltage clamped at ECl of −80 mV. B, Diary plot of postsynaptic current amplitudes over time for a single cell. Curare at 1 μm blocked synaptic activity (n = 4). C, Strychnine at 1 μm blocked synaptic activity (n = 2). D, ACV1 at 500 nm blocked synaptic activity (n = 2).

  • Figure 3.
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    Figure 3.

    Efferents contacting aged IHCs activate SK channels. A, Membrane current responses to local application of ACh at −80 mV (left) and −40 mV (right). B, Example I–V relationship of the ACh-induced current. Mean ± SEM reversal potential was −68.71 ± 0.4 mV (n = 5 cell; 2 cells at 11–12 months, 2 cells at 13–14 months, and 1 cell at 14–15 months). C, Apamin at 400 nm reduced the time constant of decay for inward synaptic currents recorded in 80 mm external K (***p < 0.001, n = 67 events across 2 recordings, 14- to 15-month-old cells).

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The Journal of Neuroscience: 35 (26)
Journal of Neuroscience
Vol. 35, Issue 26
1 Jul 2015
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Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss
Stephen Paul Zachary, Paul Albert Fuchs
Journal of Neuroscience 1 July 2015, 35 (26) 9701-9706; DOI: 10.1523/JNEUROSCI.0879-15.2015

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Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss
Stephen Paul Zachary, Paul Albert Fuchs
Journal of Neuroscience 1 July 2015, 35 (26) 9701-9706; DOI: 10.1523/JNEUROSCI.0879-15.2015
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Keywords

  • age-related hearing loss
  • cholinergic inhibition
  • cochlea
  • inner hair cell
  • olivocochlear system
  • synaptic transmission

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