Objective: To determine whether noise-induced cochlear neuropathy results in abnormal auditory behavior by measuring acoustic startle response (ASR) and prepulse inhibition (PPI) in mice exposed to neuropathic versus nonneuropathic noise intensity
Materials & Equipment Checklist
4 items2 from ConductScience
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Equipment4
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Protocol Steps
View Abstract
Perceptual abnormalities such as hyperacusis and tinnitus often occur after acoustic overexposure. Although such exposure can also result in permanent threshold elevation, some individuals with noise-induced hyperacusis or tinnitus show clinically normal thresholds. Recent work in animals has shown that a “neuropathic” noise exposure can cause immediate, permanent degeneration of the cochlear nerve despite complete threshold recovery and lack of hair cell damage (Kujawa SG, Liberman MC. J Neurosci 29: 14077–14085, 2009; Lin HW, Furman AC, Kujawa SG, Liberman MC. J Assoc Res Otolaryngol 12: 605–616, 2011). Here we ask whether this noise-induced primary neuronal degeneration results in abnormal auditory behavior, based on the acoustic startle response (ASR) and prepulse inhibition (PPI) of startle. Responses were measured in mice exposed either to a “neuropathic” noise or to a lower-intensity, “nonneuropathic” noise and in unexposed control mice. Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed controllike responses. Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies, inconsistent with the presence of tinnitus “filling in the gap.” Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem. Considering the rapid postexposure onset of both cochlear neuropathy and exaggerated startle-based behavior, the results suggest a role for cochlear primary neuronal degeneration, per se, in the central neural excitability that could underlie the generation of hyperacusis.
1
Divide mice into experimental groups
Assign mice to three groups: unexposed control mice, mice to receive neuropathic noise exposure, and mice to receive nonneuropathic noise exposure
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Note: Neuropathic noise is higher intensity; nonneuropathic noise is lower intensity
View evidence from paper
“Responses were measured in mice exposed either to a neuropathic noise or to a lower-intensity, nonneuropathic noise and in unexposed control mice”
2
Expose mice to noise
Expose designated mice to either neuropathic or nonneuropathic intensity noise. Neuropathic noise exposure causes immediate, permanent degeneration of cochlear nerve with complete threshold recovery and lack of hair cell damage. Nonneuropathic noise is lower intensity.
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Note: Neuropathic noise causes cochlear neuropathy; nonneuropathic noise does not
View evidence from paper
“a neuropathic noise exposure can cause immediate, permanent degeneration of the cochlear nerve despite complete threshold recovery and lack of hair cell damage”
3
Measure Acoustic Startle Response (ASR)
Measure acoustic startle response in all three groups of mice (control, neuropathic-exposed, nonneuropathic-exposed) to assess hyperresponsivity to sound
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Startle Response Platform
Matches: Acoustic Startle Response (ASR) measurement system
Note: Mice with cochlear neuropathy displayed enhanced ASR compared to controls
View evidence from paper
“Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed controllike responses”
4
Measure Prepulse Inhibition (PPI)
Measure prepulse inhibition of startle in all three groups of mice to assess auditory processing and potential tinnitus presence
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Note: Enhanced PPI observed in mice with cochlear neuropathy; used to assess tinnitus
View evidence from paper
“Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed controllike responses”
5
Perform Gap PPI tests
Conduct gap detection tests using prepulse inhibition paradigm to assess potential tinnitus filling in the gap phenomenon
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Note: Limited gap detection deficits observed only for certain gap-startle latencies in mice with cochlear neuropathy, inconsistent with tinnitus filling in the gap
View evidence from paper
“Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies”
6
Record Auditory Brainstem Response (ABR)
Measure auditory brainstem response including wave 1 (representing cochlear nerve activity) and later peaks (representing brainstem activity) in all groups
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Note: Wave 1 significantly reduced in neuropathic-exposed mice; later peaks unchanged or enhanced, suggesting compensatory neural hyperactivity
View evidence from paper
“Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem”
Subjects / Specimens
Species
mouse
Strain
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Age
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Sex
unknown
Weight
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Three experimental groups: unexposed control mice, mice exposed to neuropathic noise, and mice exposed to nonneuropathic noise