Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

The perception of ultrasonic vocalizations by laboratory mice following intense noise exposures.

Noise-induced hearing loss interacts with age, sex, and listening conditions to affect individuals' perception of ecologically relevant stimuli like speech. The present experiments assessed the impact of age and sex on vocalization detection by noise-exposed mice trained to detect a downsweep or complex ultrasonic vocalization in quiet or in the presence of a noise background. Daily thresholds before and following intense noise exposure were collected longitudinally and compared across several factors. All mice, regardless of age, sex, listening condition, or stimulus type showed their poorest behavioral sensitivity immediately after the noise exposure. There were varying degrees of recovery over time and across factors. Old-aged mice had greater threshold shifts and less recovery compared to middle-aged mice. Mice had larger threshold shifts and less recovery for downsweeps than for complex vocalizations. Female mice were more sensitive, had smaller post-noise shifts, and had better recovery than males. Thresholds in noise were higher and less variable than thresholds in quiet, but there were comparable shifts and recovery. In mice, as in humans, the perception of ecologically relevant stimuli suffers after an intense noise exposure, and results differ from simple tone detection findings.

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wildtype and α9α10KO mice had similar ABR thresholds and acoustic startle response (ASR) amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than wildtypes in quiet and noise, but the noise:quiet amplitude ratio suggested α9α10KOs were more susceptible to masking effects for some stimuli. α9α10KO mice also had larger startle amplitudes in tone backgrounds than wildtypes. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, though their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Auditory brainstem response (ABR) waveform analysis program.

Auditory brainstem responses (ABR) are a high-throughput assessment of auditory function. Many studies determine changes to the threshold at frequencies that span the normal hearing range of their test subjects, but fewer studies evaluate changes in waveform morphology. The goal of developing this program was to make a user-friendly semiautomatic peak-detection algorithm to encourage widespread analysis of the amplitudes and latencies of the ABR, which may yield informative details about the integrity of the auditory system with development, aging, genetic manipulations, or damaging conditions. This method incorporates automated peak detection with manual override and inter-rater validation to calculate the amplitude and latency for waves 1-5, as well as interpeak latencies and amplitude ratios between waves. The output includes raw data and calculations in a format compatible with graphical and statistical software.•The method yields a high-throughput peak-detection algorithm with manual override and inter-rater capabilities to streamline ABR waveform analysis.•Data output includes amplitudes, latencies, amplitude ratios, and interpeak latencies for generation of input-output curves.•While complete automation of peak detection with this tool is dependent on good signal-to-noise ratios, relevant amplitude and latency calculations are fully automated, and manual spot-checking is simplified to significantly reduce the time to analyze waveforms.

Physiological Evidence for Delayed Age-related Hearing Loss in Two Long-lived Rodent Species (Peromyscus leucopus and P. californicus).

Deer mice (genus Peromyscus) are an emerging model for aging studies due to their longevity relative to rodents of similar size. Although Peromyscus species are well-represented in genetic, developmental, and behavioral studies, relatively few studies have investigated auditory sensitivity in this genus. Given the potential utility of Peromyscus for investigations of age-related changes to auditory function, we recorded auditory brainstem responses (ABRs) in two Peromyscus species, P. californicus, and P. leucopus, across the lifespan. We compared hearing sensitivity and ABR wave metrics measured in these species with measurements from Mus musculus (CBA/CaJ strain) to assess age-related effects on hearing across species. Recordings in young animals showed that all species had similar hearing ranges and thresholds with peak sensitivity ranging from 8 to 16 kHz; however, P. californicus and P. leucopus were more sensitive to frequencies below 8 kHz. Although M. musculus showed significant threshold shifts across a broad range of frequencies beginning at middle age and worsening among old individuals, older Peromyscus mice retained good sensitivity to sound across their lifespan. Middle-aged P. leucopus had comparable thresholds to young for frequencies below 24 kHz. P. leucopus also had notably large ABRs that were robust to age-related amplitude reductions, although response latencies increased with age. Old P. californicus were less sensitive to mid-range tones (8-16 kHz) than young individuals; however, there were no significant age-effects on ABR amplitudes or latencies in this species. These results indicate that longevity in Peromyscus mice may be correlated with delayed aging of the auditory system and highlight these species as promising candidates for longitudinal hearing research.

Effects of Noise Exposure and Aging on Behavioral Tone Detection in Quiet and Noise by Mice.

Aging leads to degeneration of the peripheral and central auditory systems, hearing loss, and difficulty understanding sounds in noise. Aging is also associated with changes in susceptibility to or recovery from damaging noise exposures, although the effects of the interaction between acute noise exposure and age on the perception of sounds are not well studied. We tested these effects in the CBA/CaJ mouse model of age-related hearing loss using operant conditioning procedures before and after noise exposure and longitudinally measured changes in their sensitivity for detecting tones in quiet or noise backgrounds. Cochleae from a subset of the behaviorally tested mice were immunolabeled to examine organ of Corti damage relative to what is expected based on aging alone. Mice tested in both quiet and noise background conditions experienced worse behavioral sensitivity immediately after noise exposure, but mice exposed at older ages generally showed greater threshold shifts and reduced recovery over time. Surprisingly, day-to-day stability in thresholds was markedly higher for mice detecting signals in the presence of a noise masker compared with detection in quiet conditions. Cochlear analysis revealed decreases in the total number of outer hair cells (OHCs) and the number of ribbons per inner cell in high-frequency regions in aged, noise-exposed mice relative to aging alone. Our findings build on previous work showing interactions between age and noise exposure and add that background noise can increase the stability of behavioral hearing sensitivity after noise damage.

Blast trauma affects production and perception of mouse ultrasonic vocalizations.

Blast trauma from explosions affects hearing and communication in a significant proportion of soldiers. Many veterans report difficulty communicating, especially in noisy and reverberant environments, which contributes to complex mental health problems including anxiety and depression. However, the relationship between communication and perceptual problems after a blast has received little scientific attention. In the current studies, the effects of blast trauma on the production and perception of ultrasonic vocalizations (USVs) by CBA/CaJ mice, a common animal model for hearing and communication disorders, was explored. Overall, mice change the total number of vocalizations, the proportion produced of each syllable category, and the peak frequency, bandwidth, and duration of their vocalizations after blast exposure. Further, the perception of USVs is affected after blast trauma, with an immediate worsening of detection for most USV categories in the first 1-5 days after blasts, which later recovers. This study is the first to examine changes in the production and perception of communication signals after blast traumas in mice and is an important step towards developing treatments for blast-induced hearing and communication disorders.

Long term changes to auditory sensitivity following blast trauma in mice.

Blast trauma is a common acoustic/physical insult occurring in modern warfare. Twenty percent of active duty military come into close proximity to explosions and experience mild to severe sensory deficits. The prevalence of such injuries is high but correlating auditory sensitivity changes with the initial insult is difficult because injury and evaluations are often separated by long time periods. Here, auditory sensitivity was measured before and after a traumatic blast in adult CBA/CaJ mice using auditory brainstem responses, distortion production otoacoustic emissions, and behavioral detection of pure tones. These measurements included baseline auditory sensitivity prior to injury in all mice, and again at 3, 30, and 90 days after the blast in the two physiological groups, and daily for up to 90 days in the behavioral group. Mice in all groups experienced an initial deterioration in auditory sensitivity, though physiological measurements showed evidence of recovery that behavioral measurements did not. Amplitudes and latencies of ABR waves may reflect additional changes beyond the peripheral damage shown by the threshold changes and should be explored further. The present work addresses a major gap in the current acoustic trauma literature both in terms of comparing physiological and behavioral methods, as well as measuring the time course of recovery.

Sex differences in auditory brainstem response audiograms from vasopressin-deficient Brattleboro and wild-type Long-Evans rats.

Rats are highly social creatures that produce ultrasonic vocalizations (USVs) during social interactions. Brattleboro rats, a Long-Evans derived rat that lacks vasopressin (AVP) due to a mutation in the Avp gene, exhibit atypical social behavior, including fewer USVs with altered spectrotemporal characteristics during social interactions. It is unclear why Brattleboro rats produce atypical USVs, but one factor could be differences in auditory acuity between them and wild-type Long Evans rats with functional vasopressin. Previous studies have suggested a link between increased levels of AVP and auditory processing. Additionally, few studies have investigated sex differences in auditory perception by Long-Evans rats. Sex differences in auditory acuity have been found throughout the animal kingdom, but have not yet been demonstrated in rat audiograms. This study aimed to measure auditory brainstem response (ABR) derived audiograms for frequencies ranging from 1 to 64 kHz in male and female homozygous Brattleboro (Hom), heterozygous Brattleboro (Het), and wild-type (WT) Long-Evans rats to better understand the role of AVP and sex differences in auditory processing by these rats. We failed to detect significant differences between the ABR audiograms of Hom, Het, and WT Long-Evans rats, suggesting that varying levels of AVP do not affect auditory processing. Interestingly, males and females of all genotypes did differ in their ABR thresholds, with males exhibiting higher thresholds than females. The sex differences in auditory acuity were significant at the lowest and highest frequencies, possibly affecting the perception of USVs. These are the first known sex differences in rat audiograms.

Dyslexia on a continuum: A complex network approach.

We investigated the efficacy of graph-theoretic metrics of task-related functional brain connectivity in predicting reading difficulty and explored the hypothesis that task conditions emphasizing audiovisual integration would be especially diagnostic of reading difficulty. An fMRI study was conducted in which 24 children (8 to 14 years old) who were previously diagnosed with dyslexia completed a rhyming judgment task under three presentation modality conditions. Regression analyses found that characteristic connectivity metrics of the reading network showed a presentation modality dependent relationship with reading difficulty: Children with more segregated reading networks and those that used fewer of the available connections were those with the least severe reading difficulty. These results are consistent with the hypothesis that a lack of coordinated processing between the neural regions involved in phonological and orthographic processing contributes towards reading difficulty.

CBA/CaJ mouse ultrasonic vocalizations depend on prior social experience.

Mouse ultrasonic vocalizations (USVs) have variable spectrotemporal features, which researchers use to parse them into different categories. USVs may be important for communication, but it is unclear whether the categories that researchers have developed are relevant to the mice. Instead, other properties such as the number, rate, peak frequency, or bandwidth of the vocalizations may be important cues that the mice are using to interpret the nature of the social interaction. To investigate this, a comprehensive catalog of the USVs that mice are producing across different social contexts must be created. Forty male and female adult CBA/CaJ mice were recorded in isolation for five minutes following either a one-hour period of isolation or an exposure to a same- or opposite-sex mouse. Vocalizations were separated into nine categories based on the frequency composition of each USV. Additionally, USVs were quantified based on the bandwidth, duration, peak frequency, total number, and proportion of vocalizations produced. Results indicate that mice differentially produce their vocalizations across social encounters. There were significant differences in the number of USVs that mice produce across exposure conditions, the proportional probability of producing the different categories of USVs across sex and conditions, and the features of the USVs across conditions. In sum, there are sex-specific differences in production of USVs by laboratory mice, and prior social experiences matter for vocalization production. Furthermore, this study provides critical evidence that female mice probably produce vocalizations in opposite-sex interactions, which is important because this is an often overlooked variable in mouse communication research.