Publications by authors named "Timothy A Jones"

Presbycusis is a prevalent condition in older adults characterized by the progressive loss of hearing due to age-related changes in the cochlea, the auditory portion of the inner ear. Many adults also struggle with understanding speech in noise despite having normal auditory thresholds, a condition termed "hidden" hearing loss because it evades standard audiological assessments. Examination of animal models and postmortem human tissue suggests that hidden hearing loss is also associated with age-related changes in the cochlea and may, therefore, precede overt age-related hearing loss.

View Article and Find Full Text PDF

Recording the linear vestibular sensory evoked potential (VsEP) relies on moving the head in a prescribed manner to synchronously activate neurons of the gravity receptor organs. One problematic issue in accomplishing this is the potential coactivation of cochlear neurons. Although the major stimulus parameters required to elicit the vestibular response have been characterized, some of the determinants of auditory coactivation have not been clearly addressed.

View Article and Find Full Text PDF

Management of vestibular dysfunction may include treatment with medications that are thought to act to suppress vestibular function and reduce or eliminate abnormal sensitivity to head motions. The extent to which vestibular medications act centrally or peripherally is still debated. In this study, two commonly prescribed medications, meclizine and diazepam, and a candidate for future clinical use, JNJ7777120, were evaluated for their effects on short latency compound action potentials generated by the peripheral vestibular system and corresponding central neural relays (i.

View Article and Find Full Text PDF

Background: Otoconia-related vertigo and balance deficits are common in humans, but the molecular etiology is unknown at present.

Objective: In order to study mechanisms of otoconia formation and maintenance, we have investigated whether otoconin-90 (Oc90), the predominant otoconial constituent protein, and the NADPH oxidase Nox3, an essential regulatory protein for otoconia formation, are functionally interlinked.

Methods: We performed balance behavioral, electrophysiological, morphological and molecular cellular analyses.

View Article and Find Full Text PDF

The cupula is a gelatinous membrane overlying the crista ampullaris of the semicircular canal, important for sensing rotation of the head and critical for normal balance. Recently the zona pellucida like domain containing 1 protein (ZPLD1, also known as cupulin) was identified in the cupula of fish. Here, we describe two new spontaneous mutations in the mouse Zpld1 gene, which were discovered by the circling behavior of mutant mice, an indicator of balance dysfunction.

View Article and Find Full Text PDF

Antisense oligonucleotides (ASOs) have shown potential as therapeutic molecules for the treatment of inner ear dysfunction. The peripheral sensory organs responsible for both hearing and equilibrium are housed within the inner ear. Hearing loss and vestibular balance problems affect a large portion of the population and limited treatment options exist.

View Article and Find Full Text PDF

Potassium (K) channels shape the response properties of neurons. Although enormous progress has been made to characterize K channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and single molecule fluorescent in situ hybridization, we localized expression of transcripts encoding the sodium-activated potassium channels K1.

View Article and Find Full Text PDF

The injectable anesthetic mixture ketamine-xylazine is commonly used for electrophysiologic experiments in laboratory animals, especially rodents. General anesthesia can induce significant changes in systemic physiology, including those that compromise neural function, thus introducing research confounds. The extent of such concerns varies by agent.

View Article and Find Full Text PDF

Specific pharmacological blockade of KCNQ (Kv7) channels with XE991 rapidly (within 20 min) and profoundly alters inner ear gravity receptor responses to head motion (Lee et al., 2017). We hypothesized that these effects were attributable to the suppression of K secretion following blockade of KCNQ1-KCNE1 channels in vestibular dark cells and marginal cells.

View Article and Find Full Text PDF

The use of pharmacological agents is often the preferred approach to the management of vestibular dysfunction. In the vestibular sensory pathways, the sensory neuroepithelia are thought to be influenced by a diverse number of neuroactive substances that may act to enhance or inhibit the effect of the primary neurotransmitters [i.e.

View Article and Find Full Text PDF

The precise role and mechanisms underlying efferent modulation of peripheral vestibular afferent function are not well understood in mammals. Clarifying the details of efferent action may lead to new strategies for clinical management of debilitating disturbances in vestibular and balance function. Recent evidence in turtle indicates that efferent modulation of M-currents is likely one mechanism for modifying afferent discharge.

View Article and Find Full Text PDF

Usher syndrome type 1C (USH1C/harmonin) is associated with profound retinal, auditory and vestibular dysfunction. We have previously reported on an antisense oligonucleotide (ASO-29) that dramatically improves auditory function and balance behavior in mice homozygous for the harmonin mutation Ush1c c.216G > A following a single systemic administration.

View Article and Find Full Text PDF

Little is known about the function of the cholinergic efferents innervating peripheral vestibular hair cells. We measured vestibular sensory evoked potentials (VsEPs) in α9 knockout (KO) mice, α10 KO mice, α7 KO mice, α9/10 and α7/9 double KO mice, and wild-type (WT) controls. We also studied the morphology and ultrastructure of efferent terminals on vestibular hair cells in α9, α10, and α9/10 KOs.

View Article and Find Full Text PDF

The C57BL/6J (B6) mouse strain carries a cadherin 23 mutation (Cdh23(753A), also known as Ahl), which affects inner ear structures and results in age-related hearing loss. The B6.CAST strain harbors the wild type Cdh23 gene, and hence, the influence of Ahl is absent.

View Article and Find Full Text PDF

The DFNB31 gene plays an indispensable role in the cochlea and retina. Mutations in this gene disrupt its various isoforms and lead to non-syndromic deafness, blindness and deaf-blindness. However, the known expression of Dfnb31, the mouse ortholog of DFNB31, in vestibular organs and the potential vestibular-deficient phenotype observed in one Dfnb31 mutant mouse (Dfnb31(wi/wi)) suggest that DFNB31 may also be important for vestibular function.

View Article and Find Full Text PDF

Vestibular macular sensors are activated by a shearing motion between the otoconial membrane and underlying receptor epithelium. Shearing motion and sensory activation in response to an externally induced head motion do not occur instantaneously. The mechanically reactive elastic and inertial properties of the intervening tissue introduce temporal constraints on the transfer of the stimulus to sensors.

View Article and Find Full Text PDF

A/J mice develop progressive hearing loss that begins before 1 month of age and is attributed to cochlear hair cell degeneration. Screening tests indicated that this strain also develops early onset vestibular dysfunction and has otoconial deficits. The purpose of this study was to characterize the vestibular dysfunction and macular structural pathology over the lifespan of A/J mice.

View Article and Find Full Text PDF

Shank proteins (1-3) are considered the master organizers of glutamatergic postsynaptic densities in the central nervous system, and the genetic deletion of either Shank1, 2, or 3 results in altered composition, form, and strength of glutamatergic postsynapses. To investigate the contribution of Shank proteins to glutamatergic afferent synapses of the inner ear and especially cochlea, we used immunofluorescence and quantitative real time PCR to determine the expression of Shank1, 2, and 3 in the cochlea. Because we found evidence for expression of Shank1 but not 2 and 3, we investigated the morphology, composition, and function of afferent postsynaptic densities from defined tonotopic regions in the cochlea of Shank1(-/-) mice.

View Article and Find Full Text PDF

Background: The vestibular sensory-evoked potential (VsEP) is an electrical potential that provides a direct test of vestibular function in animals. VsEP recordings are carried out using subcutaneous stainless steel electrodes placed over the nuchal crest (noninverting), behind either the left or right pinna (inverting), and at the hip (ground). A noninvasive head clip is used to secure the head to a mechanical shaker for delivery of a linear vestibular stimulus measured in units of jerk (g/msec).

View Article and Find Full Text PDF

Background: A considerable amount of research has been published about genetic hearing impairment. Fifty to sixty percent of hearing loss is thought to have a genetic cause. Genes may also play a significant role in acquired hearing loss due to aging, noise exposure, or ototoxic medications.

View Article and Find Full Text PDF

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals.

View Article and Find Full Text PDF

Objective: The purpose of this study was to measure real-ear aided and saturated responses of SpeechEasy™ devices and compare responses while devices delivered altered auditory feedback (AAF) and non-altered feedback (NAF).

Design: A repeated measures quasi-experimental design was employed.

Study Sample: Ten people fitted with completely-in-the-canal or open fit behind-the-ear devices participated.

View Article and Find Full Text PDF

Short latency linear vestibular sensory evoked potentials (VsEPs) provide a means to objectively and directly assess the function of gravity receptors in mammals and birds. The importance of this functional measure is illustrated by its use in studies of the genetic basis of vestibular function and disease. Head motion is the stimulus for the VsEP.

View Article and Find Full Text PDF

The CBA/CaJ mouse strain is commonly used as a control as it has no known genetic mutations affecting the inner ear, maintains hearing sensitivity throughout life, and serves as a background for creating new genetic strains. The purpose of the present study was to characterize the effects of age and gender on gravity receptor function and compare functional changes between auditory and vestibular modalities. Vestibular-evoked potentials (VsEPs), auditory brainstem responses (ABRs), and distortion product otoacoustic emissions were measured in 131 mice.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: