Biomedical subjects

Anne E Luebke

Publications and source records attributed to Anne E Luebke.

6 recordsLinked to original sources

PubMed2003

Loss of alpha CGRP reduces sound-evoked activity in the cochlear nerve.

alpha-Calcitonin gene-related peptide (alphaCGRP) is one of several neurotransmitters immunolocalized in the unmyelinated component of the cochlear efferent innervation, the lateral olivocochlear (OC) system, which makes axo-dendritic synapses with cochlear sensory neurons. In rodents, CGRP is also immunocolocalized in the myelinated medial OC system, which contacts cochlear outer hair cells (OHCs). To understand the role(s) of this neuropeptide in the OC system, we characterized the auditory phenotype of alphaCGRP-null mice. Cochlear threshold sensitivity was normal in mutant mice, both via a neural metric, the auditory brain stem response (ABR), and an OHC-based metric, distortion product otoacoustic emissions (DPOAEs). Medial OC function and resistance to acoustic injury were also unaffected by alphaCGRP deletion: the former was assessed by measuring cochlear response suppression with electrical stimulation of the OC bundle, the latter by measuring temporary threshold shifts after exposure to high level sound. However, significant abnormality in alphaCGRP-null mice was seen in the growth of cochlear neural responses with increasing stimulus level. This observation, contrasted with normal amplitude-versus-level functions for DPOAEs, is consistent with a selective, postsynaptic effect on cochlear neurons via alphaCGRP release from lateral OC terminals. This constitutes the most direct evidence to date for a functional role of the lateral OC system in the auditory periphery.

Acoustic Stimulation↗

PubMed2002

Efferent protection from acoustic injury is mediated via alpha9 nicotinic acetylcholine receptors on outer hair cells.

Exposure to intense sound can damage the mechanosensors of the inner ear and their afferent innervation. These neurosensory elements are innervated by a sound-activated feedback pathway, the olivocochlear efferent system. One major component of this system is cholinergic, and known cholinergic effects are mediated by the alpha9/alpha10 nicotinic acetylcholine receptor (nAChR) complex. Here, we show that overexpression of alpha9 nAChR in the outer hair cells of bacterial artificial chromosome transgenic mice significantly reduces acoustic injury from exposures causing either temporary or permanent damage, without changing pre-exposure cochlear sensitivity to low- or moderate-level sound. These data demonstrate that efferent protection is mediated via the alpha9 nAChR in the outer hair cells and provide direct evidence for a protective role, in vivo, of a member of the nAChR family.

Amino Acid Sequence↗

PubMed2002

Variation in inter-animal susceptibility to noise damage is associated with alpha 9 acetylcholine receptor subunit expression level.

Large intersubject variabilities in acoustic injury are known to occur in both humans and animals; however, the mechanisms underlying such differences are poorly understood. The olivocochlear efferent system has been hypothesized to play a significant role in protecting the cochlea from noise overexposure. In this study, we demonstrate that a newly developed test for determining average efferent system strength can predict intersubject variations in acoustic injury. In addition, the intersubject variability in cochlear expression of the alpha9 subunit of the nicotinic acetylcholine receptor was found to be proportional to an animals average efferent strength. Therefore, the inter-animal variability in the alpha9-containing acetylcholine receptor expression may be one mechanism contributing to the inter-animal variability in acoustic injury.

Acoustic Stimulation↗

PubMed2002

A multifrequency method for determining cochlear efferent activity.

A test based on measures of distortion-product otoacoustic emissions (DPOAEs) was developed in lightly anesthetized guinea pigs and alert rabbits to assess the effective activation or functional "strength" of the cochlear efferent system. The multifrequency method described here used the DP-gram frequency function to evaluate the fast component of the olivocochlear adaptive effect on DPOAE levels over a 2-octave frequency range. An estimate of any concurrent muscle activation was also determined over the identical frequency range by monitoring the levels of the eliciting f1 primary tone throughout its duration. The acoustic reflex, as measured by this f1 level constancy test, did not appear to contribute to the average efferent strength of sedated guinea pigs, but the acoustic reflex did contribute to the average "efferent" strength of awake rabbits. Hence, the average efferent effect in alert rabbits is contaminated by the acoustic reflex, which confounds its interpretation.

Acoustic Stimulation↗

PubMed2002

CGRP- and cholinergic-containing fibers project to guinea pig outer hair cells.

MU33, an antibody to calcitonin gene-related peptide (CGRP), was used to investigate the magnitude of CGRP-containing nerve fiber endings, compared to acetylcholinesterase (AChE)-containing nerve fiber endings on outer hair cells (OHCs). Results showed that CGRP-containing nerve fiber immunoreactivity mimicked the AChE fiber OHC staining pattern across the cochlea suggesting that CGRP can function as both a medial efferent (contacting primarily OHCs) and as a lateral efferent (contacting primarily inner hair cell afferents) neurotransmitter.

Acetylcholinesterase↗

PubMed2002

A model for perilymphatic fistula induced hearing loss in the guinea pig cochlea.

In cases of sudden, reversible hearing loss where perilymphatic fistulas are thought to be the cause, a multitude of causes have been postulated. These include perilymphatic pressure changes, Simmons' double-break theory, perilymphatic hemorrhage, pneumolabyrinth, and others. This study was proposed to explore the role pneumolabyrinth may have in this pathology. Guinea pigs were fitted with cochlear perfusion pumps pumping artificial perilymph into the left scala tympani. One group of animals received a bubble ( approximately 1.5-2 microl) introduced into the scala tympani while the other group of animals received continuous infusion of artificial perilymph. The animals' cochlear function was monitored using distortion product otoacoustic emissions (DPOAEs) while the animals' behavior was assessed to evaluate for vestibular dysfunction. While unaffected by pump surgery, animals that received air into the scala tympani had their DPOAEs eliminated by day 2 after pump placement. On day 6, positional changes in the DPOAEs were observed where the left lateral decubitus position showed a sharp demarcation at 4 kHz, where lower DPOAE frequencies were abolished and higher ones minimally affected, with DPOAEs normal in the prone position. By days 8 and 20, DPOAEs recovered to normal amplitudes. Vestibular dysfunction was never detected in any animal that received a pneumolabyrinth. All control animals receiving a continuous perilymph infusion exhibited no loss of cochlear function throughout the testing period. The reversible nature of pneumolabyrinth induced hearing loss and the pneumolabyrinth's sole presence (without other possible causes of hearing loss, such as pressure differentials or round window membrane perforations) are powerful indicators of the role of air in the pathology of perilymphatic fistulas. In addition, the fluctuation of the hearing loss with positional changes supports the use of positional audiometry when evaluating perilymphatic fistulas.

Air↗