Abstract
Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (–/–)] or expressing an overactive receptor [Ld'T mutation in α9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [αCGRP (–/–)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult αCGRP (–/–) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (–/–) α9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (α9 nAChR KI) and are increased in adult mice lacking αCGRP (–/–). However, in background noise, only mice lacking αCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between α9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.
Highlights
15% of American adults report some degree of difficulty hearing in a noisy environment (Fausti et al, 2005; NIDCD, 2010)
We have examined pre-pulse inhibition (PPI) abilities in mice either lacking the MOC receptor subunit α9 nicotinic acetylcholine receptor [α9 nAChR (–/–) null] that have been backcrossed to the CBA strain, (Elgoyhen et al, 1994) or mice expressing an overactive receptor [Ld’T mutation in α9 nAChR KI] that are in the FVB strain (Taranda et al, 2009)
We have described a hearing-in-noise test that can be used in the mouse model, which makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR to assess the mouse’s ability to detect prepulse signals presented in quiet or embedded in masking noise
Summary
15% of American adults report some degree of difficulty hearing in a noisy environment (Fausti et al, 2005; NIDCD, 2010). There are objective tests of hearing-in-noise or auditory filtering abilities for the human population, yet, few such tests exist for mouse models that do not rely on extensive training. Such a lack of hearing-in-noise assessments in the mouse model can inhibit its use to understand the molecular underpinnings that may underlie auditory filtering abilities. The lateral system (LOC) contains three neurotransmitters, namely ACh, GABA, and alpha Calcitonin Gene-Related peptide (CGRP), and fibers containing these neurotransmitters project from the auditory brainstem to the cochlear afferent nerve. Loss of either the MOC or LOC system after cochlear development does not affect auditory thresholds, yet both systems are activated by sound. Sound suppresses MOC responses (as assessed by otoacoustic emissions and cochlear action potentials and nerve activity) and CGRP transmission through the LOC system has been shown to enhance suprathreshold cochlear nerve activity suggesting that both systems may work in tandem to enhance behavioral responses to sound (Maison et al, 2002, 2003a; Guinan et al, 2005; Guinan, 2006, 2010, 2013, 2014; Le Prell et al, 2014a,b; Dickerson et al, 2016)
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