Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Prell, Colleen G. Le; Hughes, Larry F.; Dolan, David F.; Bledsoe, Sanford C.

doi:10.3389/fcell.2021.752963

Cited by 9 publications

(7 citation statements)

References 117 publications

(192 reference statements)

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“…The effects of LOC signals in the cochlea may be similarly multifaceted. Although dopamine appears to inhibit SGN activity (15,31), acetylcholine and CGRP seems to increase afferent excitability (69)(70)(71)(72)(73)(74)(75). Moreover, analysis of dopamine receptor mutant mouse lines 4E & 5E).…”

Section: Discussionmentioning

confidence: 99%

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

Sitko,

Frank,

Romero

et al. 2024

Preprint

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The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium. One population of OCNs, the lateral olivocochlear (LOC) neurons, target spiral ganglion neurons (SGNs), the primary sensory neurons of the ear. LOCs alter their transmitter expression for days to weeks in response to noise exposure (NE), suggesting that they are well-positioned to tune SGN excitability over long time periods in response to auditory experience. To examine how LOCs affect auditory function after NE, we characterized the transcriptional profiles of OCNs and found that LOCs exhibit transient changes in gene expression after NE, including upregulation of multiple neuropeptide-encoding genes. Next, by generating intersectional mouse lines that selectively target LOCs, we chemogenetically ablated LOC neurons and assayed auditory responses at baseline and after NE. Compared to controls, mice lacking LOCs showed stronger NE-induced functional deficits one day later and had worse auditory function after a two-week recovery period. The number of remaining presynaptic puncta at the SGN synapse with inner hair cells did not differ between control and LOC-ablated animals, suggesting that the primary role of LOCs after NE is likely not one of protection, but one of compensation, ensuring that SGN function is enhanced during periods of need.

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Section: Discussionmentioning

confidence: 99%

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

Sitko,

Frank,

Romero

et al. 2024

Preprint

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“…The administration of a CGRP-receptor antagonist (BIBN4096BS) was shown to be effective in alleviating these symptoms of vestibular dysfunction and allodynia in this same NTG rat model (Tian R et al, 2022;Zhang Y et al, 2020). In addition, a recent study suggests CGRP has an excitatory role in the auditory nerve response, as CGRP infusion was shown to enhance spontaneous and sound-driven auditory nerve activity in guinea pigs, in comparison to CGRP-null mice where a loss of excitation is observed (Allen PD and Luebke AE, 2017;Le Prell CG et al, 2021). Thus, the auditory nerve may be sensitized to CGRP’s effects during a migranous state.…”

Section: Discussionmentioning

confidence: 99%

Systemic Calcitonin Gene-Related Peptide (CGRP) modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities

Rahman

Liang

Faucher

et al. 2022

Preprint

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About 42% of people with migraine have a vestibular component causing balance problems and dizziness. In fact, VM is a major cause of vertigo in dizziness clinics and is estimated to affect 1% of the overall population. As migraine increases light, and sound sensitivities, it also increases sensitivities to movement or perceived movement in VM Patients with migraine, and especially VM, exhibit a heightened sense of sound, or phonophobia. Phonophobia is also related to hyperacusis (extreme sensitivity to sound). Behavioral evidence of hyperacusis and phonophobia in mice can be inferred using the acoustic startle reflex (ASR). The most common symptoms of VM were unsteadiness, balance disturbances, and light headedness. When balance disturbances were quantified, VM patients swayed more than migraine-only or healthy controls, when challenged with competing stimulus. In addition to static imbalance, VM patients also showed dynamic imbalances such as gait disturbances. In this study, we tested wildtype C57B6/J mice to determine if mice exhibited increased sound (measured by acoustic startle), static imbalance (measured by postural sway), and dynamic imbalance (measured by rotarod), when challenged with systemic CGRP (IP) 0.1 mg/kg. We found both sexes of mice were affected by systemic CGRP in sound and dynamic imbalance testing, yet only female mice showed increased postural sway after systemic CGRP, recapitulating the higher incidence of VM in females. These non-invasive assays of VM pave the way to further explore mechanisms of CGRP signaling in VM, and test effectiveness of migraine therapeutics in VM.

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“…A better understanding of GABA functions in both systems could help to establish parallel methods of inhibitory auditory control. Although LOC efferent function is less understood, different reports show that apart from ACh, LOC terminals also release other neurotransmitters such as GABA (Plinkert et al, 1993), serotonin (Gil-Loyzaga et al, 1997), dopamine (Wu et al, 2020), calcitonin gene-related peptide (CGRP) (Le Prell et al, 2021) and other opiod peptides (Safieddine et al, 1997;Lioudyno et al, 2002). Interestingly, an ortholog of CGRP receptor has been found to be expressed in the An.…”

Section: Comparison Between Invertebrate and Vertebrate Efferent Systemsmentioning

confidence: 99%

The auditory efferent system in mosquitoes

Loh

Ellis

et al. 2023

Front. Cell Dev. Biol.

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Whilst acoustic communication forms an integral component of the mating behavior of many insect species, it is particularly crucial for disease-transmitting mosquitoes; swarming males rely on hearing the faint sounds of flying females for courtship initiation. That males can hear females within the din of a swarm is testament to their fabulous auditory systems. Mosquito hearing is highly frequency-selective, remarkably sensitive and, most strikingly, supported by an elaborate system of auditory efferent neurons that modulate the auditory function - the only documented example amongst insects. Peripheral release of octopamine, serotonin and GABA appears to differentially modulate hearing across major disease-carrying mosquito species, with receptors from other neurotransmitter families also identified in their ears. Because mosquito mating relies on hearing the flight tones of mating partners, the auditory efferent system offers new potential targets for mosquito control. It also represents a unique insect model for studying auditory efferent networks. Here we review current knowledge of the mosquito auditory efferent system, briefly compare it with its counterparts in other species and highlight future research directions to unravel its contribution to mosquito auditory perception.

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Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity

Cited by 9 publications

References 117 publications

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

Systemic Calcitonin Gene-Related Peptide (CGRP) modifies auditory and vestibular end organ electrical potentials, and increases sensory hypersensitivities

The auditory efferent system in mosquitoes

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