Abstract
Calcitonin-gene-related peptide (CGRP) is a lateral olivocochlear (LOC) efferent neurotransmitter. Depression of sound-driven auditory brainstem response amplitude in CGRP-null mice suggests the potential for endogenous CGRP release to upregulate spontaneous and/or sound-driven auditory nerve (AN) activity. We chronically infused CGRP into the guinea pig cochlea and evaluated changes in AN activity as well as outer hair cell (OHC) function. The amplitude of both round window noise (a measure of ensemble spontaneous activity) and the synchronous whole-nerve response to sound (compound action potential, CAP) were enhanced. Lack of change in both onset adaptation and steady state amplitude of sound-evoked distortion product otoacoustic emission (DPOAE) responses indicated CGRP had no effect on OHCs, suggesting the origin of the observed changes was neural. Combined with results from the CGRP-null mice, these results appear to confirm that endogenous CGRP enhances auditory nerve activity when released by the LOC neurons. However, infusion of the CGRP receptor antagonist CGRP (8–37) did not reliably influence spontaneous or sound-driven AN activity, or OHC function, results that contrast with the decreased ABR amplitude measured in CGRP-null mice.
Highlights
A variety of evidence suggests a role for Calcitonin-gene-related-peptide (CGRP) in auditory function, with CGRP released by the lateral olivocochlear (LOC) efferent neurons mediating the neural response to sound
There are some reports that CGRP-positive labeling of the LOC system is robust across the length of the guinea pig cochlea (SliwinskaKowalska et al, 1989; Ylikoski et al, 1989) there are reports that CGRP-positive cells are less abundant in the apex and upper third turn of the guinea pig cochlea (Safieddine and Eybalin, 1992)
The primary outcome reported here is an increase in compound action potential (CAP) amplitude accompanied by small improvements in CAP threshold during CGRP infusion into the cochlea
Summary
A variety of evidence suggests a role for Calcitonin-gene-related-peptide (CGRP) in auditory function, with CGRP released by the lateral olivocochlear (LOC) efferent neurons mediating the neural response to sound. LOC efferents have been immunolabeled with antibodies to CGRP in the cochlea in guinea pigs (Takeda et al, 1987; Sliwinska-Kowalska et al, 1989; Ylikoski et al, 1989; Ohno et al, 1993; Cabanillas and Luebke, 2002). Immunolabeling of the human cochlea revealed CGRP-like immunoreactivity in the inner spiral bundle and tunnel spiral bundle suggesting expression of CGRP in both the LOC and medial olivococlear (MOC) efferent neurons with no notable differences from base to apex (Schrott-Fischer et al, 2007). The lack of sex differences in that mouse study contrasts with sex differences in CGRP immunoreactivity observed in other tissues from rat and from human (Valdemarsson et al, 1990; Herbison and Spratt, 1995; Ji et al, 2019), with sex differences in humans potentially explaining sex differences in the efficacy of antimigraine medications that target CGRP receptors (Barbanti et al, 2021; de Vries Lentsch et al, 2021)
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