Behavioral Neuroscience publications

The temporal structure of sensory inputs contains essential information for their interpretation. Sensory cortex represents these temporal cues through two codes: the temporal sequences of neuronal activity and the spatial patterns of neuronal firing rate. However, it is unknown which of these coexisting codes causally drives sensory decisions. To separate their contributions, we generated in the mouse auditory cortex optogenetically driven activity patterns differing exclusively along their temporal or spatial dimensions. Mice could rapidly learn to behaviorally discriminate spatial but not temporal patterns. Moreover, large-scale neuronal recordings across the auditory system revealed that the auditory cortex is the first region in which spatial patterns efficiently represent temporal cues on the timescale of several hundred milliseconds. This feature is shared by the deep layers of neural networks categorizing time-varying sounds. Therefore, the emergence of a spatial code for temporal sensory cues is a necessary condition to efficiently associate temporally structured stimuli with decisions.

Noise exposure is one of the most common causes of hearing loss and hyperacusis. Studies have shown that noise exposure can induce a cortical gain to compensate for reduced input of the cochlea, which may contribute to the increased sound sensitivity. However, many people with hyperacusis have no measurable cochlear lesion after being exposed to loud sound. In this experiment, we studied the neurological alterations in the cortical and subcortical areas following a prolonged moderate level of noise exposure (84 dB SPL, 8 h/day for 4 weeks) in the laboratory mice. The cochlear function was monitored by auditory brainstem responses (ABRs). The behavioral auditory sensitivity and temporal processing were evaluated using the acoustic startle response (ASR) and gap‐induced prepulse inhibition (gap‐PPI). The central auditory functions were determined by electrophysiological recordings of the inferior colliculus (IC) and the auditory cortex (AC). Our results showed that although there was no significant difference in the ABR thresholds, the noise group showed enhanced ASR and gap‐PPI compared to the control group. Increased neural activity in both the IC and the AC was recorded in the noise‐exposed mice compared to the control group, suggesting a central gain in both the subcortical and cortical regions. The current source density (CSD) analysis of the AC response revealed an increased columnar excitation and reduced corticocortical projection in the noise group, different from the central gain model of noise‐induced hearing loss. Our results suggest that chronic “nondestructive” noise can increase the gain of the central auditory system by altering the balance of auditory thalamocortical and intracortical inputs, which may contribute to the increased sound sensitivity in people with normal hearing.

Hearing mediates many behaviours critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviours for survival to old age; however, relatively little is known about the ageing bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats ( Eptesicus fuscus ) and measured hearing sensitivity in young and ageing bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear ageing, with similar hair cell counts, afferent and efferent innervation patterns in young and ageing bats. Here, we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.

Background Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition. A feature that is unique in this model is that spontaneous resurfacing of the dehiscence occurs via osteoneogenesis without a subsequent intervention. In this study, we completed our assessment of this model to include reversible asymmetrical vestibular impairments that interfere with balance. Methods Adult Mongolian gerbils ( N = 6) were trained to complete a balance beam task. They were also trained to perform a Rotarod task. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Balance beam testing recommenced at postoperative day 6 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results Behavioral comparison of preoperative and postoperative performance show a significant decrease in Rotarod performance, increased rates of falling, and an increase in time to cross the balance beam. Impairments were the most significant at postoperative day 7 with a return toward preoperative performance by postoperative day 14. This behavioral impairment was correlated with residual impairments to auditory thresholds and vestibular myogenic amplitudes at postoperative day 14. Conclusion These results confirm that aberrant asymmetric vestibular output in our model of SSCD results in reversible balance impairments. The level of these behavioral impairments is directly correlated with severity of the vestibular dysfunction as we have previously reported for peripheral ear physiology and cognition.

Background Prepulse inhibition (PPI) is a phenomenon where a weak prepulse stimulus inhibits the startle reflex to a subsequent stronger stimulus, which can be induced by various sensory stimulus modalities such as visual, tactile, and auditory stimuli. Methods This study investigates the neural mechanisms underlying auditory PPI by focusing on the deep layers of the superior colliculus (deepSC) and the inferior colliculus (IC) in rats. Nineteen male Sprague-Dawley rats were implanted with electrodes in the left deepSC and the right IC, and electrophysiological recordings were conducted under anesthesia to observe the frequency following responses (FFRs) to startle stimuli with and without prepulse stimuli. Results Our results showed that in the deepSC, narrowband noise as a prepulse stimulus significantly inhibited the envelope component of the startle response, while the fine structure component remained unaffected. However, this inhibitory effect was not observed in the IC or when the prepulse stimulus was a gap. Conclusion These findings suggest that the deepSC plays a crucial role in the neural circuitry of PPI, particularly in the modulation of the envelope component of the startle response. The differential effects of narrowband noise and gap as prepulse stimuli also indicate distinct neural pathways for sound-induced PPI and Gap-PPI. Understanding these mechanisms could provide insights into sensory processing and potential therapeutic targets for disorders involving impaired PPI, such as tinnitus.

The claustrum has been linked to attention and sleep. We hypothesized that this reflects a shared function, determining responsiveness to stimuli, which spans the axis of engagement. To test this hypothesis, we recorded claustrum population dynamics from male mice during both sleep and an attentional task (‘ENGAGE’). Heightened activity in claustrum neurons projecting to the anterior cingulate cortex (ACCp) corresponded to reduced sensory responsiveness during sleep. Similarly, in the ENGAGE task, heightened ACCp activity correlated with disengagement and behavioral lapses, while low ACCp activity correlated with hyper-engagement and impulsive errors. Chemogenetic elevation of ACCp activity reduced both awakenings during sleep and impulsive errors in the ENGAGE task. Furthermore, mice employing an exploration strategy in the task showed a stronger correlation between ACCp activity and performance compared to mice employing an exploitation strategy which reduced task complexity. Our results implicate ACCp claustrum neurons in restricting engagement during sleep and goal-directed behavior.

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.

Introduction Subjective tinnitus, the perception of sound without an external acoustic source, is often subsequent to noise-induced hearing loss or ototoxic medications. The condition is believed to result from neuroplastic alterations in the auditory centers, characterized by heightened spontaneous neural activities and increased synchrony due to an imbalance between excitation and inhibition. However, the role of the thalamic reticular nucleus (TRN), a structure composed exclusively of GABAergic neurons involved in thalamocortical oscillations, in the pathogenesis of tinnitus remains largely unexplored. Methods We induced tinnitus in mice using sodium salicylate and assessed tinnitus-like behaviors using the Gap Pre-Pulse Inhibition of the Acoustic Startle (GPIAS) paradigm. We utilized combined viral tracing techniques to identify the neural circuitry involved and employed immunofluorescence and confocal imaging to determine cell types and activated neurons. Results Salicylate-treated mice exhibited tinnitus-like behaviors. Our tracing clearly delineated the inputs and outputs of the auditory-specific TRN. We discovered that chemogenetic activation of the auditory TRN significantly reduced the salicylate-evoked rise in c-Fos expression in the auditory cortex. Discussion This finding posits the TRN as a potential modulatory target for tinnitus treatment. Furthermore, the mapped sensory inputs to the auditory TRN suggest possibilities for employing optogenetic or sensory stimulations to manipulate thalamocortical activities. The precise mapping of the auditory TRN-mediated neural pathways offers a promising avenue for designing targeted interventions to alleviate tinnitus symptoms.

Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

The entorhinal cortex is involved in establishing enduring visuo-auditory associative memory in the neocortex. Here we explored the mechanisms underlying this synaptic plasticity related to projections from the visual and entorhinal cortices to the auditory cortex in mice using optogenetics of dual pathways. High-frequency laser stimulation (HFS laser) of the visuo-auditory projection did not induce long-term potentiation. However, after pairing with sound stimulus, the visuo-auditory inputs were potentiated following either infusion of cholecystokinin (CCK) or HFS laser of the entorhino-auditory CCK-expressing projection. Combining retrograde tracing and RNAscope in situ hybridization, we show that Cck expression is higher in entorhinal cortex neurons projecting to the auditory cortex than in those originating from the visual cortex. In the presence of CCK, potentiation in the neocortex occurred when the presynaptic input arrived 200 ms before postsynaptic firing, even after just five trials of pairing. Behaviorally, inactivation of the CCK + projection from the entorhinal cortex to the auditory cortex blocked the formation of visuo-auditory associative memory. Our results indicate that neocortical visuo-auditory association is formed through heterosynaptic plasticity, which depends on release of CCK in the neocortex mostly from entorhinal afferents.

The basal ganglia are essential for executing motor actions. How the basal ganglia engage spinal motor networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons are required for turning gait programs, suggesting that turning gaits organized by the basal ganglia are executed via this descending pathway. Performing deep brainstem recordings of Chx10 Gi Ca 2+ activity in adult mice, we show that striatal projection neurons initiate turning gaits via a dominant crossed pathway to Chx10 Gi neurons on the contralateral side. Using intersectional viral tracing and cell-type-specific modulation, we uncover the principal basal ganglia–spinal cord pathway for locomotor asymmetries in mice: basal ganglia → pontine reticular nucleus, oral part (PnO) → Chx10 Gi → spinal cord. Modulating the restricted PnO → Chx10 Gi pathway restores turning competence upon striatal damage, suggesting that dysfunction of this pathway may contribute to debilitating turning deficits observed in Parkinson’s disease. Our results reveal the stratified circuit architecture underlying a critical motor program.

The hearing abilities of mammals are impacted by factors such as social cues, habitat, and physical characteristics. Despite being used commonly to study social behaviors, hearing of the monogamous prairie vole (Microtus ochrogaster) has never been characterized. In this study, anatomical features are measured and auditory brainstem responses (ABRs) are used to measure auditory capabilities of prairie voles, characterizing monaural and binaural hearing and hearing range. Sexually naive male and female voles were measured to characterize differences due to sex. It was found that prairie voles show a hearing range with greatest sensitivity between 8 and 32 kHz, binaural hearing across interaural time difference ranges appropriate for their head sizes. No differences are shown between the sexes in binaural hearing or hearing range (except at 1 kHz), however, female voles have increased amplitude of peripheral ABR waves I and II and longer latency of waves III and IV compared to males. The results confirm that prairie voles have a broad hearing range, binaural hearing consistent with rodents of similar size, and differences in amplitudes and thresholds of monaural physiological measures between the sexes. These data further highlight the necessity to understand sex-specific differences in neural processing that may underly variability in responses between sexes.

Previous studies on the advantages of binaural hearing have long been focused on sound localization and spatial stream segregation. The binaural advantages have also been observed in speech perception in reverberation. Both human speech and animal vocalizations contain temporal features that are critical for speech perception and animal communication. However, whether there are binaural advantages for sound temporal information processing in the central auditory system has not been elucidated. Gap detection threshold (GDT), the ability to detect the shortest silent interval in a sound, has been widely used to measure the auditory temporal resolution. In the present study, we determined GDTs of rat inferior collicular neurons under both monaural and binaural hearing conditions. We found that the majority of the inferior collicular neurons in adult rats exhibited binaural advantages in gap detection, i.e., better neural gap detection ability in binaural hearing conditions compared to monaural hearing condition. However, this binaural advantage in sound temporal information processing was not significant in the inferior collicular neurons of P14-21 and P22-30 rats. Additionally, we also observed age-related changes in neural temporal acuity in the rat inferior colliculus. These results demonstrate a new advantage of binaural hearing (i.e., binaural advantage in temporal processing) in the central auditory system in addition to sound localization and spatial stream segregation.

Background Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD. Methods Adult Mongolian gerbils ( n = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard (“easy”) or more difficult (“hard”) auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results Behavioral data (d-primes) were compared between preoperative performance (training day 8–10) and postoperative days 6–8 and 13–15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group. Conclusion These results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.

Background: Commonly encountered nontraumatic, moderate noise is increasingly implicated in anxiety; however, the neural substrates underlying this process remain unclear. Objectives: We investigated the neural circuit mechanism through which chronic exposure to moderate-level noise causes anxiety-like behaviors. Methods: Mice were exposed to chronic, moderate white noise [85 decibel (dB) sound pressure level (SPL)], 4 h/d for 4 wk to induce anxiety-like behaviors, which were assessed by open field, elevated plus maze, light-dark box, and social interaction tests. Viral tracing, immunofluorescence confocal imaging, and brain slice patch-clamp recordings were used to characterize projections from auditory brain regions to the lateral amygdala. Neuronal activities were characterized by in vivo multielectrode and fiber photometry recordings in awake mice. Optogenetics and chemogenetics were used to manipulate specific neural circuitry. Results: Mice chronically (4 wk) exposed to moderate noise (85 dB SPL, 4 h/d) demonstrated greater neuronal activity in the lateral amygdala (LA), and the LA played a critical role in noise-induced anxiety-like behavior in these model mice. Viral tracing showed that the LA received monosynaptic projections from the medial geniculate body (MG) and auditory cortex (ACx). Optogenetic excitation of the MG→LA or ACx→LA circuits acutely evoked anxiety-like behaviors, whereas their chemogenetic inactivation abolished noise-induced anxiety-like behavior. Moreover, mice chronically exposed to moderate noise were more susceptible to acute stress, with more neuronal firing in the LA, even after noise withdrawal. Discussion: Mice exposed to 4 wk of moderate noise (85 dB SPL, 4 h/d) demonstrated behavioral and physiological differences compared to controls. The neural circuit mechanisms involved greater excitation from glutamatergic neurons of the MG and ACx to LA neurons under chronic, moderate noise exposure, which ultimately promoted anxiety-like behaviors. Our findings support the hypothesis that nontraumatic noise pollution is a potentially serious but unrecognized public health concern. https://doi.org/10.1289/EHP12532.

The ability to process and act upon incoming sounds during locomotion is critical for survival and adaptive behavior. Despite the established role that the auditory cortex (AC) plays in behavior- and context-dependent sound processing, previous studies have found that auditory cortical activity is on average suppressed during locomotion as compared to immobility. While suppression of auditory cortical responses to self-generated sounds results from corollary discharge, which weakens responses to predictable sounds, the functional role of weaker responses to unpredictable external sounds during locomotion remains unclear. In particular, whether suppression of external sound-evoked responses during locomotion reflects reduced involvement of the AC in sound processing or whether it results from masking by an alternative neural computation in this state remains unresolved. Here, we tested the hypothesis that rather than simple inhibition, reduced sound-evoked responses during locomotion reflect a tradeoff with the emergence of explicit and reliable coding of locomotion velocity. To test this hypothesis, we first used neural inactivation in behaving mice and found that the AC plays a critical role in sound-guided behavior during locomotion. To investigate the nature of this processing, we used two-photon calcium imaging of local excitatory auditory cortical neural populations in awake mice. We found that locomotion had diverse influences on activity of different neurons, with a net suppression of baseline-subtracted sound-evoked responses and neural stimulus detection, consistent with previous studies. Importantly, we found that the net inhibitory effect of locomotion on baseline-subtracted sound-evoked responses was strongly shaped by elevated ongoing activity that compressed the response dynamic range, and that rather than reflecting enhanced “noise,” this ongoing activity reliably encoded the animal’s locomotion speed. Decoding analyses revealed that locomotion speed and sound are robustly co-encoded by auditory cortical ensemble activity. Finally, we found consistent patterns of joint coding of sound and locomotion speed in electrophysiologically recorded activity in freely moving rats. Together, our data suggest that rather than being suppressed by locomotion, auditory cortical ensembles explicitly encode it alongside sound information to support sound perception during locomotion.

Introduction Conductive hearing loss (CHL) attenuates the ability to transmit air conducted sounds to the ear. In humans, severe hearing loss is often accompanied by alterations to other neural systems, such as the vestibular system; however, the inter-relations are not well understood. The overall goal of this study was to assess vestibular-related functioning proxies in a rat CHL model. Methods Male Sprague–Dawley rats ( N =134, 250g, 2months old) were used in a CHL model which produced a >20dB threshold shift induced by tympanic membrane puncture. Auditory brainstem response (ABRs) recordings were used to determine threshold depth at different times before and after CHL. ABR threshold depths were assessed both manually and by an automated ABR machine learning algorithm. Vestibular-related functioning proxy assessment was performed using the rotarod, balance beam, elevator vertical motion (EVM) and Ferris-wheel rotation (FWR) assays. Results The Pre-CHL (control) threshold depth was 27.92dB±11.58dB compared to the Post-CHL threshold depth of 50.69dB±13.98dB (mean±SD) across the frequencies tested. The automated ABR machine learning algorithm determined the following threshold depths: Pre-CHL=24.3dB, Post-CHL same day=56dB, Post-CHL 7 days=41.16dB, and Post-CHL 1 month=32.5dB across the frequencies assessed (1, 2, 4, 8, 16, and 32kHz). Rotarod assessment of motor function was not significantly different between pre and post-CHL (~1week) rats for time duration (sec) or speed (RPM), albeit the former had a small effect size difference. Balance beam time to transverse was significantly longer for post-CHL rats, likely indicating a change in motor coordination. Further, failure to cross was only noted for CHL rats. The defection count was significantly reduced for CHL rats compared to control rats following FWR, but not EVM. The total distance traveled during open-field examination after EVM was significantly different between control and CHL rats, but not for FWR. The EVM is associated with linear acceleration (acting in the vertical plane: up-down) stimulating the saccule, while the FWR is associated with angular acceleration (centrifugal rotation about a circular axis) stimulating both otolith organs and semicircular canals; therefore, the difference in results could reflect the specific vestibular-organ functional role. Discussion Less movement (EVM) and increase time to transverse (balance beam) may be associated with anxiety and alterations to defecation patterns (FWR) may result from autonomic disturbances due to the impact of hearing loss. In this regard, vestibulomotor deficits resulting in changes in balance and motion could be attributed to comodulation of auditory and vestibular functioning. Future studies should manipulate vestibular functioning directly in rats with CHL.

Background Behavior consists of the interaction between an organism and its environment, and is controlled by the brain. Brain activity varies at sub-second time scales, but behavioral measures are usually coarse (often consisting of only binary trial outcomes). Results To overcome this mismatch, we developed the Rat Interactive Foraging Facility (RIFF): a programmable interactive arena for freely moving rats with multiple feeding areas, multiple sound sources, high-resolution behavioral tracking, and simultaneous electrophysiological recordings. The paper provides detailed information about the construction of the RIFF and the software used to control it. To illustrate the flexibility of the RIFF, we describe two complex tasks implemented in the RIFF, a foraging task and a sound localization task. Rats quickly learned to obtain rewards in both tasks. Neurons in the auditory cortex as well as neurons in the auditory field in the posterior insula had sound-driven activity during behavior. Remarkably, neurons in both structures also showed sensitivity to non-auditory parameters such as location in the arena and head-to-body angle. Conclusions The RIFF provides insights into the cognitive capabilities and learning mechanisms of rats and opens the way to a better understanding of how brains control behavior. The ability to do so depends crucially on the combination of wireless electrophysiology and detailed behavioral documentation available in the RIFF.

Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards‐walking behavior in open‐field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1g bw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner‐ear hair‐cell function, including a complete lack of auditory brainstem responses and vestibular‐evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1g bw/bw mice had no substantial retinal degeneration compared with Ush1g bw /+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.

During development, early-life stress (ELS) impairs cognition, learning, and emotional regulation, in part by disrupting neural circuitry in regions underlying these higher-order functions. In addition, our recent work indicates that ELS also alters simple sensory perception: ELS impaired auditory perception and neural encoding of short gaps in sounds, which are essential for vocal communication. The combination of higher-order and basic sensory disruption suggests that ELS is likely to affect both the perception and interpretation of communication signals. We tested this hypothesis by measuring behavioral responses to conspecific vocalizations (those emitted by other gerbils) in ELS and untreated Mongolian gerbils. Because stress effects often differ by sex, we separately examined females and males. To induce ELS, pups were intermittently maternally separated and restrained from post-natal days (P) 9–24, a time window when the auditory cortex is most sensitive to external disruption. We measured the approach responses of juvenile (P31–32) gerbils to two types of conspecific vocalizations: an alarm call, which is emitted to alert other gerbils of a potential threat, and the prosocial contact call, which is emitted near familiar gerbils, especially after separation. Control males, Control females, and ELS females approached a speaker emitting pre-recorded alarm calls, while ELS males avoided this source, suggesting that ELS affects the response to alarm calls in male gerbils. During playback of the pre-recorded contact call, Control females and ELS males avoided the sound source, while Control males neither approached nor avoided, and ELS females approached the sound. These differences cannot be accounted for by changes in locomotion or baseline arousal. However, ELS gerbils slept more during playback, suggesting that ELS may reduce arousal during vocalization playback. Further, male gerbils made more errors than females on a measure of working memory, but the sex difference of cognition in this context may stem from novelty aversion rather than impaired memory. These data indicate that ELS influences behavioral responses to ethologically relevant communication sounds in a sex-specific manner, and are among the first to demonstrate an altered response to auditory stimuli following ELS. Such changes may arise from differences in auditory perception, cognition, or a combination of factors, and suggest that ELS may affect auditory communication in human adolescents.