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.

Sources of variability in auditory brainstem response thresholds in a mouse model of noise-induced hearing loss.

Numerous and non-acoustic experimental factors can potentially influence experimental outcomes in animal models when measuring the effects of noise exposures. Subject-related factors, including species, strain, age, sex, body weight, and post-exposure measurement timepoints, influence the observed hearing deficits. Experimenter effects, such as experience with experimental techniques and animal handling, may also factor into reported thresholds. In this study, the influence of subject sex, body mass, age at noise exposure, and timepoint of post-exposure recording are reported from a large sample of CBA/CaJ mice. Auditory brainstem response (ABR) thresholds differed between noise-exposed and unexposed mice, although the differences varied across tone frequencies. Thresholds across age at noise exposures and measurement delays after exposure also differed for some timepoints. Higher body mass correlated with higher ABR thresholds for unexposed male and female mice, but not for noise-exposed mice. Together, these factors may contribute to differences in phenotypic outcomes observed across studies or even within a single laboratory.

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.

Dimensionally Specific Attention Capture in Birds Performing Auditory Streaming Task.

Previous studies in budgerigars (Melopsittacus undulatus) have indicated that they experience attention capture in a qualitatively similar way to humans. Here, we apply a similar objective auditory streaming paradigm, using modified budgerigar vocalizations instead of ABAB-… patterned pure tones, in the sound sequences. The birds were trained to respond to deviants in the target stream while ignoring the distractors in the background stream. The background distractor could vary among five different categories and two different sequential positions, while the target deviants could randomly appear at five different sequential positions and vary among two different categories. We found that unpredictable background distractors could deteriorate birds' sensitivity to the target deviants. Compared to conditions where the background distractor appeared right before the target deviant, the attention capture effect decayed in conditions when the background distractor appeared earlier. In contrast to results from the same paradigm using pure tones, the results here are evidence for a faster recovery from attention capture using modified vocalization segments. We found that the temporally modulated background distractor captured birds' attention more and deteriorated birds' performance more than other categories of background distractor, as the temporally modulated target deviant enabled the birds to focus their attention toward the temporal modulation dimension. However, different from humans, birds have lower tolerances for suppressing the distractors from the same feature dimensions as the targets, which is evidenced by higher false alarm rates for the temporally modulated distractor than other distractors from different feature dimensions.

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.

Linking anatomical and physiological markers of auditory system degeneration with behavioral hearing assessments in a mouse (Mus musculus) model of age-related hearing loss.

Age-related hearing loss is a very common sensory disability, affecting one in three older adults. Establishing a link between anatomical, physiological, and behavioral markers of presbycusis in a mouse model can improve the understanding of this disorder in humans. We measured age-related hearing loss for a variety of acoustic signals in quiet and noisy environments using an operant conditioning procedure and investigated the status of peripheral structures in CBA/CaJ mice. Mice showed the greatest degree of hearing loss in the last third of their lifespan, with higher thresholds in noisy than in quiet conditions. Changes in auditory brainstem response thresholds and waveform morphology preceded behavioral hearing loss onset. Loss of hair cells, auditory nerve fibers, and signs of stria vascularis degeneration were observed in old mice. The present work underscores the difficulty in ascribing the primary cause of age-related hearing loss to any particular type of cellular degeneration. Revealing these complex structure-function relationships is critical for establishing successful intervention strategies to restore hearing or prevent presbycusis.

Attention capture in birds performing an auditory streaming task.

Numerous animal models have been used to investigate the neural mechanisms of auditory processing in complex acoustic environments, but it is unclear whether an animal's auditory attention is functionally similar to a human's in processing competing auditory scenes. Here we investigated the effects of attention capture in birds performing an objective auditory streaming paradigm. The classical ABAB… patterned pure tone sequences were modified and used for the task. We trained the birds to selectively attend to a target stream and only respond to the deviant appearing in the target stream, even though their attention may be captured by a deviant in the background stream. When no deviant appeared in the background stream, the birds experience the buildup of streaming process in a qualitatively similar way as they did in a subjective paradigm. Although the birds were trained to selectively attend to the target stream, they failed to avoid the involuntary attention switch caused by the background deviant, especially when the background deviant was sequentially unpredictable. Their global performance deteriorated more with increasingly salient background deviants, where the buildup process was reset by the background distractor. Moreover, sequential predictability of the background deviant facilitated the recovery of the buildup process after attention capture. This is the first study that addresses the perceptual consequences of the joint effects of top-down and bottom-up attention in behaving animals.

Best sensitivity of temporal modulation transfer functions in laboratory mice matches the amplitude modulation embedded in vocalizations.

The perception of spectrotemporal changes is crucial for distinguishing between acoustic signals, including vocalizations. Temporal modulation transfer functions (TMTFs) have been measured in many species and reveal that the discrimination of amplitude modulation suffers at rapid modulation frequencies. TMTFs were measured in six CBA/CaJ mice in an operant conditioning procedure, where mice were trained to discriminate an 800 ms amplitude modulated white noise target from a continuous noise background. TMTFs of mice show a bandpass characteristic, with an upper limit cutoff frequency of around 567 Hz. Within the measured modulation frequencies ranging from 5 Hz to 1280 Hz, the mice show a best sensitivity for amplitude modulation at around 160 Hz. To look for a possible parallel evolution between sound perception and production in living organisms, we also analyzed the components of amplitude modulations embedded in natural ultrasonic vocalizations (USVs) emitted by this strain. We found that the cutoff frequency of amplitude modulation in most of the individual USVs is around their most sensitive range obtained from the psychoacoustic experiments. Further analyses of the duration and modulation frequency ranges of USVs indicated that the broader the frequency ranges of amplitude modulation in natural USVs, the shorter the durations of the USVs.

The effects of age and sex on the detection of pure tones by adult CBA/CaJ mice (Mus musculus).

Age-related hearing loss (ARHL) is a neurodegenerative disorder characterized by a gradual decrease in hearing sensitivity. Previous electrophysiological and behavioral studies have demonstrated that the CBA/CaJ mouse strain is an appropriate model for the late-onset hearing loss found in humans. However, few studies have characterized hearing in these mice behaviorally using longitudinal methodologies. The goal of this research was to utilize a longitudinal design and operant conditioning procedures with positive reinforcement to construct audiograms and temporal integration functions in aging CBA/CaJ mice. In the first experiment, thresholds were collected for 8, 16, 24, 42, and 64 kHz pure tones in 30 male and 35 female CBA/CaJ mice. Similar to humans, mice had higher thresholds for high frequency tones than for low frequency pure tones across the lifespan. Female mice had better hearing acuity than males after 645 days of age. In the second experiment, temporal integration functions were constructed for 18 male and 18 female mice for 16 and 64 kHz tones varying in duration. Mice showed an increase in thresholds for tones shorter than 200 ms, reaching peak performance at shorter durations than other rodent species. Overall, CBA/CaJ mice experience ARHL for pure tones of different frequencies and durations, making them a good model for studies on hearing loss. These findings highlight the importance of using a wide range of stimuli and a longitudinal design when comparing presbycusis across different species.

Perception of Ultrasonic Vocalizations by Socially Housed and Isolated Mice.

It is currently unclear whether mice use their ultrasonic vocalizations (USVs) for communication purposes. It is also unknown whether mice require previous experience with USVs to understand conspecifics. There is some evidence that experience changes the perception of juvenile USVs; however, it is unclear whether similar plasticity also occurs for adult USVs. To examine whether social exposure or deprivation throughout development leads to changes in USV perception, eleven female CBA/CaJ mice were trained to discriminate between 18 USVs of three different categories using operant conditioning procedures. Mice were group housed with four females or housed individually from weaning for the duration of the experiment. Socially housed and isolated mice differed in initial training times on pure tones, suggesting isolated mice had a more difficult time learning the task. Both groups completed USV discrimination conditions quicker at the end of the testing phases relative to the beginning. The overall discrimination of USVs did not differ between the two housing conditions, but a multidimensional scaling analysis revealed that socially experienced and isolated mice perceive some USVs differently, illustrated by differences in locations of USVs on the scaling maps from the two groups. Finally, a negative correlation was found between spectrotemporal similarity and percent discrimination, and analyses support the idea that mice may show categorical perception of at least two of the three USV categories. Thus, experience with USVs changes USV perception.

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.

Social isolation produces no effect on ultrasonic vocalization production in adult female CBA/CaJ mice.

Mice produce ultrasonic vocalizations (USVs) in a wide variety of social contexts, including courtship, investigation, and territorial defense. Despite the belief that mouse USVs are innate, social experience may be necessary for mice to learn the appropriate situation to emit USVs. Mouse USVs have been divided into categories based on their spectrotemporal parameters, but it is currently unclear if social experience changes these parameters (e.g., frequency and duration) or the proportion of calls from each category produced. Social isolation has been found to influence USV production in male mice. To investigate the influence of social isolation on vocal behavior in female mice, recordings were made of USVs emitted to unfamiliar male and female mice by subjects with one of three types of social experience. Twenty-four adult female CBA/CaJ mice either lived alone, lived with other females only, or lived with other females and had limited access to a male. Mice were recorded while in isolation, ensuring all recorded USVs were from the female of interest. Vocalizations were separated into nine categories and peak frequency, duration, and bandwidth were measured for every call. Socially isolated mice did not produce significantly more USVs or USV types than socially experienced mice. Social isolation did not have a significant effect on the features of USVs, suggesting production of USVs may not be learned in female mice.

Effects of Non-traumatic Noise and Conductive Hearing Loss on Auditory System Function.

The effects of traumatic noise-exposure and deafening on auditory system function have received a great deal of attention. However, lower levels of noise as well as temporary conductive hearing loss also have consequences on auditory physiology and hearing. Here we review how abnormal acoustic experience at early ages affects the ascending and descending auditory pathways, as well as hearing behavior.

Behavioral measurements of auditory streaming and build-up by budgerigars (Melopsittacus undulatus).

The perception of the build-up of auditory streaming has been widely investigated in humans, while it is unknown whether animals experience a similar perception when hearing high (H) and low (L) tonal pattern sequences. The paradigm previously used in European starlings (Sturnus vulgaris) was adopted in two experiments to address the build-up of auditory streaming in budgerigars (Melopsittacus undulatus). In experiment 1, different numbers of repetitions of low-high-low triplets were used in five conditions to study the build-up process. In experiment 2, 5 and 15 repetitions of high-low-high triplets were used to investigate the effects of repetition rate, frequency separation, and frequency range of the two tones on the birds' streaming perception. Similar to humans, budgerigars subjectively experienced the build-up process in auditory streaming; faster repetition rates and larger frequency separations enhanced the streaming perception, and these results were consistent across the two frequency ranges. Response latency analysis indicated that the budgerigars needed a longer amount of time to respond to stimuli that elicited a salient streaming perception. These results indicate, for the first time using a behavioral paradigm, that budgerigars experience a build-up of auditory streaming in a manner similar to humans.

Preference in female laboratory mice is influenced by social experience.

Mice must perceive and interpret the signals they are presented with to evaluate potential mates, and should show a preference for high quality conspecifics. The present experiment was designed to investigate preference for acoustic, olfactory, and acoustic + olfactory signals in laboratory mice. Eighteen female CBA/CaJ mice, socially housed or isolated, were tested to evaluate preference for signals produced by males. Social experience influenced female preference for male USV playback and soiled bedding. Female mice who had experience with males showed a stronger preference for olfactory signals, whereas female mice with experience only with other females preferred USV playback. Isolated mice showed a greater preference for signals of different modalities presented together than socially experienced mice. This preference may have occurred because of increased motivation to make social contact. The findings of this experiment illustrate that social experience could play a role in mate choice.

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.

Intensity difference limens in adult CBA/CaJ mice (Mus musculus).

Mice have emerged as important models of auditory perception and acoustic communication. To study and model complex sound perception and communication, basic hearing abilities have to be established, yet intensity difference limens have not been measured in CBA/CaJ mice. Nine mice were trained using operant conditioning procedures with positive reinforcement to discriminate sound intensity across frequencies. Intensity difference limens were measured for 12, 16, 24, and 42 kHz tones at 10 and 30 dB sensation levels. Mice are capable of discriminating intensities across frequencies and sensation levels, but have higher intensity difference limens (IDLs) thresholds than other mammals.

Correction: Experience with speech sounds is not necessary for cue trading by budgerigars (Melopsittacus undulatus).

[This corrects the article DOI: 10.1371/journal.pone.0177676.].

Experience with speech sounds is not necessary for cue trading by budgerigars (Melopsittacus undulatus).

The influence of experience with human speech sounds on speech perception in budgerigars, vocal mimics whose speech exposure can be tightly controlled in a laboratory setting, was measured. Budgerigars were divided into groups that differed in auditory exposure and then tested on a cue-trading identification paradigm with synthetic speech. Phonetic cue trading is a perceptual phenomenon observed when changes on one cue dimension are offset by changes in another cue dimension while still maintaining the same phonetic percept. The current study examined whether budgerigars would trade the cues of voice onset time (VOT) and the first formant onset frequency when identifying syllable initial stop consonants and if this would be influenced by exposure to speech sounds. There were a total of four different exposure groups: No speech exposure (completely isolated), Passive speech exposure (regular exposure to human speech), and two Speech-trained groups. After the exposure period, all budgerigars were tested for phonetic cue trading using operant conditioning procedures. Birds were trained to peck keys in response to different synthetic speech sounds that began with "d" or "t" and varied in VOT and frequency of the first formant at voicing onset. Once training performance criteria were met, budgerigars were presented with the entire intermediate series, including ambiguous sounds. Responses on these trials were used to determine which speech cues were used, if a trading relation between VOT and the onset frequency of the first formant was present, and whether speech exposure had an influence on perception. Cue trading was found in all birds and these results were largely similar to those of a group of humans. Results indicated that prior speech experience was not a requirement for cue trading by budgerigars. The results are consistent with theories that explain phonetic cue trading in terms of a rich auditory encoding of the speech signal.