Assessment of auditory and vestibular damage in a mouse model after single and triple blast exposures.

The use of explosive devices in war and terrorism has increased exposure to concussive blasts among both military personnel and civilians, which can cause permanent hearing and balance deficits that adversely affect survivors' quality of life. Significant knowledge gaps on the underlying etiology of blast-induced hearing loss and balance disorders remain, especially with regard to the effect of blast exposure on the vestibular system, the impact of multiple blast exposures, and long-term recovery. To address this, we investigated the effects of blast exposure on the inner ear using a mouse model in conjunction with a high-fidelity blast simulator. Anesthetized animals were subjected to single or triple blast exposures, and physiological measurements and tissue were collected over the course of recovery for up to 180 days. Auditory brainstem responses (ABRs) indicated significantly elevated thresholds across multiple frequencies. Limited recovery was observed at low frequencies in single-blasted mice. Distortion Product Otoacoustic Emissions (DPOAEs) were initially absent in all blast-exposed mice, but low-amplitude DPOAEs could be detected at low frequencies in some single-blast mice by 30 days post-blast, and in some triple-blast mice at 180 days post-blast. All blast-exposed mice showed signs of Tympanic Membrane (TM) rupture immediately following exposure and loss of outer hair cells (OHCs) in the basal cochlear turn. In contrast, the number of Inner Hair Cells (IHCs) and spiral ganglion neurons was unchanged following blast-exposure. A significant reduction in IHC pre-synaptic puncta was observed in the upper turns of blast-exposed cochleae. Finally, we found no significant loss of utricular hair cells or changes in vestibular function as assessed by vestibular evoked potentials. Our results suggest that (1) blast exposure can cause severe, long-term hearing loss which may be partially due to slow TM healing or altered mechanical properties of healed TMs, (2) traumatic levels of sound can still reach the inner ear and cause basal OHC loss despite middle ear dysfunction caused by TM rupture, (3) blast exposure may result in synaptopathy in humans, and (4) balance deficits after blast exposure may be primarily due to traumatic brain injury, rather than damage to the peripheral vestibular system.

Short-term NAD+ supplementation prevents hearing loss in mouse models of Cockayne syndrome.

Age-related hearing loss (ARHL) is one of the most common disorders affecting elderly individuals. There is an urgent need for effective preventive measures for ARHL because none are currently available. Cockayne syndrome (CS) is a premature aging disease that presents with progressive hearing loss at a young age, but is otherwise similar to ARHL. There are two human genetic complementation groups of CS, A and B. While the clinical phenotypes in patients are similar, the proteins have very diverse functions, and insight into their convergence is of great interest. Here, we use mouse models for CS (CSA -/- and CSB m/m ) that recapitulate the hearing loss in human CS patients. We previously showed that NAD+, a key metabolite with various essential functions, is reduced in CS and associated with multiple CS phenotypes. In this study, we report that NAD+ levels are reduced in the cochlea of CSB m/m mice and that short-term treatment (10 days) with the NAD+ precursor nicotinamide riboside (NR), prevents hearing loss, restores outer hair cell loss, and improves cochlear health in CSB m/m mice. Similar, but more modest effects were observed in CSA -/- mice. Remarkably, we observed a reduction in synaptic ribbon counts in the presynaptic zones of inner hair cells in both CSA -/- and CSB m/m mice, pointing to a converging mechanism for cochlear defects in CS. Ribbon synapses facilitate rapid and sustained synaptic transmission over long periods of time. Ribeye, a core protein of synaptic ribbons, possesses an NAD(H) binding pocket which regulates its activity. Intriguingly, NAD+ supplementation rescues reduced synaptic ribbon formation in both CSA -/- and CSB m/m mutant cochleae. These findings provide valuable insight into the mechanism of CS- and ARHL-associated hearing loss, and suggest a possible intervention.

Age-dependent gene expression in the inner ear of big brown bats (Eptesicus fuscus).

For echolocating bats, hearing is essential for survival. Specializations for detecting and processing high frequency sounds are apparent throughout their auditory systems. Recent studies on echolocating mammals have reported evidence of parallel evolution in some hearing-related genes in which distantly related groups of echolocating animals (bats and toothed whales), cluster together in gene trees due to apparent amino acid convergence. However, molecular adaptations can occur not only in coding sequences, but also in the regulation of gene expression. The aim of this study was to examine the expression of hearing-related genes in the inner ear of developing big brown bats, Eptesicus fuscus, during the period in which echolocation vocalizations increase dramatically in frequency. We found that seven genes were significantly upregulated in juveniles relative to adults, and that the expression of four genes through development correlated with estimated age. Compared to available data for mice, it appears that expression of some hearing genes is extended in juvenile bats. These results are consistent with a prolonged growth period required to develop larger cochlea relative to body size, a later maturation of high frequency hearing, and a greater dependence on high frequency hearing in echolocating bats.

Big brown bats (Eptesicus fuscus) reveal diverse strategies for sonar target tracking in clutter.

Bats actively adjust the acoustic features of their sonar calls to control echo information specific to a given task and environment. A previous study investigated how bats adapted their echolocation behavior when tracking a moving target in the presence of a stationary distracter at different distances and angular offsets. The use of only one distracter, however, left open the possibility that a bat could reduce the interference of the distracter by turning its head. Here, bats tracked a moving target in the presence of one or two symmetrically placed distracters to investigate adaptive echolocation behavior in a situation where vocalizing off-axis would result in increased interference from distracter echoes. Both bats reduced bandwidth and duration but increased sweep rate in more challenging distracter conditions, and surprisingly, made more head turns in the two-distracter condition compared to one, but only when distracters were placed at large angular offsets. However, for most variables examined, subjects showed distinct strategies to reduce clutter interference, either by (1) changing spectral or temporal features of their calls, or (2) producing large numbers of sonar sound groups and consistent head-turning behavior. The results suggest that individual bats can use different strategies for target tracking in cluttered environments.

Spatial perception and adaptive sonar behavior.

Bat echolocation is a dynamic behavior that allows for real-time adaptations in the timing and spectro-temporal design of sonar signals in response to a particular task and environment. To enable detailed, quantitative analyses of adaptive sonar behavior, echolocation call design was investigated in big brown bats, trained to rest on a stationary platform and track a tethered mealworm that approached from a starting distance of about 170 cm in the presence of a stationary sonar distracter. The distracter was presented at different angular offsets and distances from the bat. The results of this study show that the distance and the angular offset of the distracter influence sonar vocalization parameters of the big brown bat, Eptesicus fuscus. Specifically, the bat adjusted its call duration to the closer of two objects, distracter or insect target, and the magnitude of the adjustment depended on the angular offset of the distracter. In contrast, the bat consistently adjusted its call rate to the distance of the insect, even when this target was positioned behind the distracter. The results hold implications for understanding spatial information processing and perception by echolocation.