Can Extensive Training Transform a Mouse into a Guinea Pig? An Evaluation Based on the Discriminative Abilities of Inferior Colliculus Neurons.

Humans and animals maintain accurate discrimination between communication sounds in the presence of loud sources of background noise. In previous studies performed in anesthetized guinea pigs, we showed that, in the auditory pathway, the highest discriminative abilities between conspecific vocalizations were found in the inferior colliculus. Here, we trained CBA/J mice in a Go/No-Go task to discriminate between two similar guinea pig whistles, first in quiet conditions, then in two types of noise, a stationary noise and a chorus noise at three SNRs. Control mice were passively exposed to the same number of whistles as trained mice. After three months of extensive training, inferior colliculus (IC) neurons were recorded under anesthesia and the responses were quantified as in our previous studies. In quiet, the mean values of the firing rate, the temporal reliability and mutual information obtained from trained mice were higher than from the exposed mice and the guinea pigs. In stationary and chorus noise, there were only a few differences between the trained mice and the guinea pigs; and the lowest mean values of the parameters were found in the exposed mice. These results suggest that behavioral training can trigger plasticity in IC that allows mice neurons to reach guinea pig-like discrimination abilities.

Behavioral and functional assessment of mice inner ear after chronic exposure to an ultrahigh B0 field of 11.7 T or 17.2 T.

PURPOSE: Assess short-term and long-term effects of chronic exposure to an ultrahigh static magnetic (B0 ) field on mice inner ear in the context of MR safety of human scanning at 11.7 T. METHODS: Mice were chronically exposed to a B0 field of 11.7 T or 17.2 T during ten 2-h exposure sessions evenly distributed over a period of 5 weeks, resulting in a total of 20 h of exposure per mouse. During exposure sessions, mice were anesthetized and positioned either parallel or antiparallel to B0 . Before, during, and 2 weeks after the magnetic-field exposure period, mice performed behavioral tests (balance beam, rotarod, and swim tests) to evaluate their short-term and long-term motor coordination and balance. An auditory brainstem response (ABR) test was finally performed to assess the functional integrity of mice cochlea, 2 weeks after the last exposure. RESULTS: After awaking from anesthesia following B0 exposures at 11.7 Tor 17.2 T, mice displayed a transient (<5 min) rotating behavior. The behavioral tests did not show any difference between the exposed and the control mice at any time point. Determination of ABR thresholds did not reveal an impairment of cochlea hair cells resulting from chronic B0 exposure. CONCLUSION: Despite the transient disturbance of mice vestibular system observed immediately after B0 exposure, no short-term nor long-term alteration was detected with behavioral and ABR tests.

What Is the Benefit of Ramped Pulse Shapes for Activating Auditory Cortex Neurons? An Electrophysiological Study in an Animal Model of Cochlear Implant.

In all commercial cochlear implant (CI) devices, the activation of auditory nerve fibers is performed with rectangular pulses that have two phases of opposite polarity. Recently, several papers proposed that ramped pulse shapes could be an alternative shape for efficiently activating auditory nerve fibers. Here, we investigate whether ramped pulse shapes can activate auditory cortex (ACx) neurons in a more efficient way than the classical rectangular pulses. Guinea pigs were implanted with CI devices and responses of ACx neurons were tested with rectangular pulses and with four ramped pulse shapes, with a first-phase being either cathodic or anodic. The thresholds, i.e., the charge level necessary for obtaining significant cortical responses, were almost systematically lower with ramped pulses than with rectangular pulses. The maximal firing rate (FR) elicited by the ramped pulses was higher than with rectangular pulses. As the maximal FR occurred with lower charge levels, the dynamic range (between threshold and the maximal FR) was not modified. These effects were obtained with cathodic and anodic ramped pulses. By reducing the charge levels required to activate ACx neurons, the ramped pulse shapes should reduce charge consumption and should contribute to more battery-efficient CI devices in the future.

Reduction in sound discrimination in noise is related to envelope similarity and not to a decrease in envelope tracking abilities.

Humans and animals constantly face challenging acoustic environments, such as various background noises, that impair the detection, discrimination and identification of behaviourally relevant sounds. Here, we disentangled the role of temporal envelope tracking in the reduction in neuronal and behavioural discrimination between communication sounds in situations of acoustic degradations. By collecting neuronal activity from six different levels of the auditory system, from the auditory nerve up to the secondary auditory cortex, in anaesthetized guinea-pigs, we found that tracking of slow changes of the temporal envelope is a general functional property of auditory neurons for encoding communication sounds in quiet conditions and in adverse, challenging conditions. Results from a go/no-go sound discrimination task in mice support the idea that the loss of distinct slow envelope cues in noisy conditions impacted the discrimination performance. Together, these results suggest that envelope tracking is potentially a universal mechanism operating in the central auditory system, which allows the detection of any between-stimulus difference in the slow envelope and thus copes with degraded conditions. KEY POINTS: In quiet conditions, envelope tracking in the low amplitude modulation range (<20 Hz) is correlated with the neuronal discrimination between communication sounds as quantified by mutual information from the cochlear nucleus up to the auditory cortex. At each level of the auditory system, auditory neurons retain their abilities to track the communication sound envelopes in situations of acoustic degradation, such as vocoding and the addition of masking noises up to a signal-to-noise ratio of -10 dB. In noisy conditions, the increase in between-stimulus envelope similarity explains the reduction in both behavioural and neuronal discrimination in the auditory system. Envelope tracking can be viewed as a universal mechanism that allows neural and behavioural discrimination as long as the temporal envelope of communication sounds displays some differences.

Unexpected Motherhood-Triggered Hearing Loss in the Two-Pore Channel (TPC) Mutant Mouse.

Calcium signaling is crucial for many physiological processes and can mobilize intracellular calcium stores in response to environmental sensory stimuli. The endolysosomal two-pore channel (TPC), regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP), is one of the key components in calcium signaling. However, its role in neuronal physiology remains largely unknown. Here, we investigated to what extent the acoustic thresholds differed between the WT mice and the TPC KO mice. We determined the thresholds based on the auditory brainstem responses (ABRs) at five frequencies (between 4 and 32 kHz) and found no threshold difference between the WT and KO in virgin female mice. Surprisingly, in lactating mothers (at P9-P10), the thresholds were higher from 8 to 32 kHz in the TPC KO mice compared to the WT mice. This result indicates that in the TPC KO mice, physiological events occurring during parturition altered the detection of sounds already at the brainstem level, or even earlier.

Exposure to 1800 MHz LTE electromagnetic fields under proinflammatory conditions decreases the response strength and increases the acoustic threshold of auditory cortical neurons.

Increased needs for mobile phone communications have raised successive generations (G) of wireless technologies, which could differentially affect biological systems. To test this, we exposed rats to single head-only exposure of a 4G long-term evolution (LTE)-1800 MHz electromagnetic field (EMF) for 2 h. We then assessed the impact on microglial space coverage and electrophysiological neuronal activity in the primary auditory cortex (ACx), under acute neuroinflammation induced by lipopolysaccharide. The mean specific absorption rate in the ACx was 0.5 W/kg. Multiunit recording revealed that LTE-EMF triggered reduction in the response strength to pure tones and to natural vocalizations, together with an increase in acoustic threshold in the low and medium frequencies. Iba1 immunohistochemistry showed no change in the area covered by microglia cell bodies and processes. In healthy rats, the same LTE-exposure induced no change in response strength and acoustic threshold. Our data indicate that acute neuroinflammation sensitizes neuronal responses to LTE-EMF, which leads to an altered processing of acoustic stimuli in the ACx.

Increased Threshold and Reduced Firing Rate of Auditory Cortex Neurons after Cochlear Implant Insertion.

The cochlear implant (CI) is the most successful neuroprosthesis allowing thousands of patients with profound hearing loss to recover speech understanding. Recently, cochlear implants have been proposed to subjects with residual hearing and, in these cases, shorter CIs were implanted. To be successful, it is crucial to preserve the patient's remaining hearing abilities after the implantation. Here, we quantified the effects of CI insertion on the responses of auditory cortex neurons in anesthetized guinea pigs. The responses of auditory cortex neurons were determined before and after the insertion of a 300 µm diameter CI (six stimulating electrodes, length 6 mm). Immediately after CI insertion there was a 5 to 15 dB increase in the threshold for cortical neurons from the middle to the high frequencies, accompanied by a decrease in the evoked firing rate. Analyzing the characteristic frequency (CF) values revealed that in large number of cases, the CFs obtained after insertion were lower than before. These effects were not detected in the control animals. These results indicate that there is a small but immediate cortical hearing loss after CI insertion, even with short length CIs. Therefore, efforts should be made to minimize the damages during CI insertion to preserve the cortical responses to acoustic stimuli.

Temporal Alterations to Central Auditory Processing without Synaptopathy after Lifetime Exposure to Environmental Noise.

People are increasingly exposed to environmental noise through the cumulation of occupational and recreational activities, which is considered harmless to the auditory system, if the sound intensity remains <80 dB. However, recent evidence of noise-induced peripheral synaptic damage and central reorganizations in the auditory cortex, despite normal audiometry results, has cast doubt on the innocuousness of lifetime exposure to environmental noise. We addressed this issue by exposing adult rats to realistic and nontraumatic environmental noise, within the daily permissible noise exposure limit for humans (80 dB sound pressure level, 8 h/day) for between 3 and 18 months. We found that temporary hearing loss could be detected after 6 months of daily exposure, without leading to permanent hearing loss or to missing synaptic ribbons in cochlear hair cells. The degraded temporal representation of sounds in the auditory cortex after 18 months of exposure was very different from the effects observed after only 3 months of exposure, suggesting that modifications to the neural code continue throughout a lifetime of exposure to noise.

When and How Does the Auditory Cortex Influence Subcortical Auditory Structures? New Insights About the Roles of Descending Cortical Projections.

For decades, the corticofugal descending projections have been anatomically well described but their functional role remains a puzzling question. In this review, we will first describe the contributions of neuronal networks in representing communication sounds in various types of degraded acoustic conditions from the cochlear nucleus to the primary and secondary auditory cortex. In such situations, the discrimination abilities of collicular and thalamic neurons are clearly better than those of cortical neurons although the latter remain very little affected by degraded acoustic conditions. Second, we will report the functional effects resulting from activating or inactivating corticofugal projections on functional properties of subcortical neurons. In general, modest effects have been observed in anesthetized and in awake, passively listening, animals. In contrast, in behavioral tasks including challenging conditions, behavioral performance was severely reduced by removing or transiently silencing the corticofugal descending projections. This suggests that the discriminative abilities of subcortical neurons may be sufficient in many acoustic situations. It is only in particularly challenging situations, either due to the task difficulties and/or to the degraded acoustic conditions that the corticofugal descending connections bring additional abilities. Here, we propose that it is both the top-down influences from the prefrontal cortex, and those from the neuromodulatory systems, which allow the cortical descending projections to impact behavioral performance in reshaping the functional circuitry of subcortical structures. We aim at proposing potential scenarios to explain how, and under which circumstances, these projections impact on subcortical processing and on behavioral responses.

Enhanced Discriminative Abilities of Auditory Cortex Neurons for Pup Calls Despite Reduced Evoked Responses in C57BL/6 Mother Mice.

A fundamental task for the auditory system is to process communication sounds according to their behavioral significance. In many mammalian species, pup calls became more significant for mothers than other conspecific and heterospecific communication sounds. To study the cortical consequences of motherhood on the processing of communication sounds, we recorded neuronal responses in the primary auditory cortex of virgin and mother C57BL/6 mice which had similar ABR thresholds. In mothers, the evoked firing rate in response to pure tones was decreased and the frequency receptive fields were narrower. The responses to pup and adult calls were also reduced but the amount of mutual information (MI) per spike about the pup call's identity was increased in mother mice. The response latency to pup and adult calls was significantly shorter in mothers. Despite similarly decreased responses to guinea pig whistles, the response latency, and the MI per spike did not differ between virgins and mothers for these heterospecific vocalizations. Noise correlations between cortical recordings were decreased in mothers, suggesting that the firing rate of distant neurons was more independent from each other. Together, these results indicate that in the most commonly used mouse strain for behavioral studies, the discrimination of pup calls by auditory cortex neurons is more efficient during motherhood.

Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds.

KEY POINTS: Enhancing cortical excitability can be achieved by either reducing intracortical inhibition or by enhancing intracortical excitation. Here we compare the consequences of reducing intracortical inhibition and of enhancing intracortical excitation on the processing of communication sounds in the primary auditory cortex. Local application of gabazine and of AMPA enlarged the spectrotemporal receptive fields and increased the responses to communication to the same extent. The Mutual Information (an index of the cortical neurons' ability to discriminate between natural sounds) was increased in both cases, as were the noise and signal correlations. Spike-timing reliability was only increased after gabazine application and post-excitation suppression was affected in the opposite way: it was increased when reducing the intracortical inhibition but was eliminated by enhancing the excitation. A computational model suggests that these results can be explained by an additive effect vs. a multiplicative effect ABSTRACT: The level of excitability of cortical circuits is often viewed as one of the critical factors controlling perceptive performance. In theory, enhancing cortical excitability can be achieved either by reducing inhibitory currents or by increasing excitatory currents. Here, we evaluated whether reducing inhibitory currents or increasing excitatory currents in auditory cortex similarly affects the neurons' ability to discriminate between communication sounds. We attenuated the inhibitory currents by application of gabazine (GBZ), and increased the excitatory currents by applying AMPA in the auditory cortex while testing frequency receptive fields and responses to communication sounds. GBZ and AMPA enlarged the receptive fields and increased the responses to communication sounds to the same extent. The spike-timing reliability of neuronal responses was largely increased when attenuating the intracortical inhibition but not after increasing the excitation. The discriminative abilities of cortical cells increased in both cases but this increase was more pronounced after attenuating the inhibition. The shape of the response to communication sounds was modified in the opposite direction: reducing inhibition increased post-excitation suppression whereas this suppression tended to disappear when increasing the excitation. A computational model indicates that the additive effect promoted by AMPA vs. the multiplicative effect of GBZ on neuronal responses, together with the dynamics of spontaneous cortical activity, can explain these differences. Thus, although apparently equivalent for increasing cortical excitability, acting on inhibition vs. on excitation impacts differently the cortical ability to discriminate natural stimuli, and only modulating inhibition changed efficiently the cortical representation of communication sounds.

Noise-Sensitive But More Precise Subcortical Representations Coexist with Robust Cortical Encoding of Natural Vocalizations.

Humans and animals maintain accurate sound discrimination in the presence of loud sources of background noise. It is commonly assumed that this ability relies on the robustness of auditory cortex responses. However, only a few attempts have been made to characterize neural discrimination of communication sounds masked by noise at each stage of the auditory system and to quantify the noise effects on the neuronal discrimination in terms of alterations in amplitude modulations. Here, we measured neural discrimination between communication sounds masked by a vocalization-shaped stationary noise from multiunit responses recorded in the cochlear nucleus, inferior colliculus, auditory thalamus, and primary and secondary auditory cortex at several signal-to-noise ratios (SNRs) in anesthetized male or female guinea pigs. Masking noise decreased sound discrimination of neuronal populations in each auditory structure, but collicular and thalamic populations showed better performance than cortical populations at each SNR. In contrast, in each auditory structure, discrimination by neuronal populations was slightly decreased when tone-vocoded vocalizations were tested. These results shed new light on the specific contributions of subcortical structures to robust sound encoding, and suggest that the distortion of slow amplitude modulation cues conveyed by communication sounds is one of the factors constraining the neuronal discrimination in subcortical and cortical levels.SIGNIFICANCE STATEMENT Dissecting how auditory neurons discriminate communication sounds in noise is a major goal in auditory neuroscience. Robust sound coding in noise is often viewed as a specific property of cortical networks, although this remains to be demonstrated. Here, we tested the discrimination performance of neuronal populations at five levels of the auditory system in response to conspecific vocalizations masked by noise. In each acoustic condition, subcortical neurons better discriminated target vocalizations than cortical ones and in each structure, the reduction in discrimination performance was related to the reduction in slow amplitude modulation cues.

Effects of a Single Head Exposure to GSM-1800 MHz Signals on the Transcriptome Profile in the Rat Cerebral Cortex: Enhanced Gene Responses Under Proinflammatory Conditions.

Mobile communications are propagated by electromagnetic fields (EMFs), and since the 1990s, they operate with pulse-modulated signals such as the GSM-1800 MHz. The biological effects of GSM-EMF in humans affected by neuropathological processes remain seldom investigated. In this study, a 2-h head-only exposure to GSM-1800 MHz was applied to (i) rats undergoing an acute neuroinflammation triggered by a lipopolysaccharide (LPS) treatment, (ii) age-matched healthy rats, or (iii) transgenic hSOD1G93A rats that modeled a presymptomatic phase of human amyotrophic lateral sclerosis (ALS). Gene responses were assessed 24 h after the GSM head-only exposure in a motor area of the cerebral cortex (mCx) where the mean specific absorption rate (SAR) was estimated to be 3.22 W/kg. In LPS-treated rats, a genome-wide mRNA profiling was performed by RNA-seq analysis and revealed significant (adjusted p value < 0.05) but moderate (fold changes < 2) upregulations or downregulations affecting 2.7% of the expressed genes, including genes expressed predominantly in neuronal or in glial cell types and groups of genes involved in protein ubiquitination or dephosphorylation. Reverse transcription-quantitative PCR analyses confirmed gene modulations uncovered by RNA-seq data and showed that in a set of 15 PCR-assessed genes, significant gene responses to GSM-1800 MHz depended upon the acute neuroinflammatory state triggered in LPS-treated rats, because they were not observed in healthy or in hSOD1G93A rats. Together, our data specify the extent of cortical gene modulations triggered by GSM-EMF in the course of an acute neuroinflammation and indicate that GSM-induced gene responses can differ according to pathologies affecting the CNS.

Neural code: Another breach in the wall?

Brette presents arguments that query the existence of the neural code. However, he has neglected certain evidence that could be viewed as proof that a neural code operates in the brain. Albeit these proofs show a link between neural activity and cognition, we discuss why they fail to demonstrate the existence of an invariant neural code.

Neuronal Encoding in a High-Level Auditory Area: From Sequential Order of Elements to Grammatical Structure.

Sensitivity to the sequential structure of communication sounds is fundamental not only for language comprehension in humans but also for song recognition in songbirds. By quantifying single-unit responses, we first assessed whether the sequential order of song elements, called syllables, in conspecific songs is encoded in a secondary auditory cortex-like region of the zebra finch brain. Based on a habituation/dishabituation paradigm, we show that, after multiple repetitions of the same conspecific song, rearranging syllable order reinstated strong responses. A large proportion of neurons showed sensitivity to song context in which syllables occurred providing support for the nonlinear processing of syllable sequences. Sensitivity to the temporal order of items within a sequence should enable learning its underlying structure, an ability considered a core mechanism of the human language faculty. We show that repetitions of songs that were ordered according to a specific grammatical structure (i.e., ABAB or AABB structures; A and B denoting song syllables) led to different responses in both anesthetized and awake birds. Once responses were decreased due to song repetitions, the transition from one structure to the other could affect the firing rates and/or the spike patterns. Our results suggest that detection was based on local differences rather than encoding of the global song structure as a whole. Our study demonstrates that a high-level auditory region provides neuronal mechanisms to help discriminate stimuli that differ in their sequential structure.SIGNIFICANCE STATEMENT Sequence processing has been proposed as a potential precursor of language syntax. As a sequencing operation, the encoding of the temporal order of items within a sequence may help in recognition of relationships between adjacent items and in learning the underlying structure. Taking advantage of the stimulus-specific adaptation phenomenon observed in a high-level auditory region of the zebra finch brain, we addressed this question at the neuronal level. Reordering elements within conspecific songs reinstated robust responses. Neurons also detected changes in the structure of artificial songs, and this detection depended on local transitions between adjacent or nonadjacent syllables. These findings establish the songbird as a model system for deciphering the mechanisms underlying sequence processing at the single-cell level.

A multiscale analysis in CD38-/- mice unveils major prefrontal cortex dysfunctions.

Autism spectrum disorder (ASD) is characterized by early onset of behavioral and cognitive alterations. Low plasma levels of oxytocin (OT) have also been found in ASD patients; recently, a critical role for the enzyme CD38 in the regulation of OT release was demonstrated. CD38 is important in regulating several Ca2+-dependent pathways, but beyond its role in regulating OT secretion, it is not known whether a deficit in CD38 expression leads to functional modifications of the prefrontal cortex (PFC), a structure involved in social behavior. Here, we report that CD38-/- male mice show an abnormal cortex development, an excitation-inhibition balance shifted toward a higher excitation, and impaired synaptic plasticity in the PFC such as those observed in various mouse models of ASD. We also show that a lack of CD38 alters social behavior and emotional responses. Finally, examining neuromodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38-/- adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38-/- mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD.-Martucci, L. L., Amar, M., Chaussenot, R., Benet, G., Bauer, O., de Zélicourt, A., Nosjean, A., Launay, J.-M., Callebert, J., Sebrié, C., Galione, A., Edeline, J.-M., de la Porte, S., Fossier, P., Granon, S., Vaillend, C., Cancela, J.-M., A multiscale analysis in CD38-/- mice unveils major prefrontal cortex dysfunctions.

ECAP growth function to increasing pulse amplitude or pulse duration demonstrates large inter-animal variability that is reflected in auditory cortex of the guinea pig.

Despite remarkable advances made to ameliorate how cochlear implants process the acoustic environment, many improvements can still be made. One of most fundamental questions concerns a strategy to simulate an increase in sound intensity. Psychoacoustic studies indicated that acting on either the current, or the duration of the stimulating pulses leads to perception of changes in how loud the sound is. The present study compared the growth function of electrically evoked Compound Action Potentials (eCAP) of the 8th nerve using these two strategies to increase electrical charges (and potentially to increase the sound intensity). Both with chronically (experiment 1) or acutely (experiment 2) implanted guinea pigs, only a few differences were observed between the mean eCAP amplitude growth functions obtained with the two strategies. However, both in chronic and acute experiments, many animals showed larger increases of eCAP amplitude with current increase, whereas some animals showed larger of eCAP amplitude with duration increase, and other animals show no difference between either approaches. This indicates that the parameters allowing the largest increase in eCAP amplitude considerably differ between subjects. In addition, there was a significant correlation between the strength of neuronal firing rate in auditory cortex and the effect of these two strategies on the eCAP amplitude. This suggests that pre-selecting only one strategy for recruiting auditory nerve fibers in a given subject might not be appropriate for all human subjects.

A Single Exposure to GSM-1800 MHz Signals in the Course of an Acute Neuroinflammatory Reaction can Alter Neuronal Responses and Microglial Morphology in the Rat Primary Auditory Cortex.

During mobile phone conversations, the temporal lobe neural networks involved in processing auditory information are exposed to electromagnetic fields (EMF) such as pulse-modulated GSM-1800 MHz radiofrequencies that convey wireless communications. The effects of these EMF on the brain affected by a pathological condition remain little investigated. In this study, rats injected with lipopolysaccharide (LPS) to induce neuroinflammation were exposed "head-only" to GSM-1800 MHz signals for two hours at a specific absorption rate (SAR) that reached an average value of 1.55 W/kg in the auditory cortex (ACx). Immunodetection of Iba1, a microglial marker, and electrophysiological recordings in the ACx three to six hours after global system for communication (GSM) exposure, or sham-exposure, showed that exposure to GSM-1800 MHz resulted in a growth of microglial processes and a reduction in spontaneous firing rate. More importantly, there was a significant reduction in evoked responses to artificial and natural stimuli and an increase in response duration. The response latency and the bandwidth of the frequency tuning were unchanged, but the GSM exposure led to a higher proportion of cortical sites exhibiting abnormally high acoustic thresholds. These modifications were not observed in rats exposed to GSM-1800 MHz without pretreatment with LPS. Together our data provide evidence that in neuroinflammatory conditions, acute exposure to GSM-1800 MHz can significantly affect microglia and neuronal activity underling auditory perception.

Assessment of the efficacy of a local steroid rescue treatment administered 2 days after a moderate noise-induced trauma in guinea pig.

OBJECTIVES: Intratympanic injection of corticosteroids membrane after noise-induced hearing loss is an accepted alternative to general administration. We investigated the effect on hearing of a hyaluronic acid gel with liposomes loaded with dexamethasone (DexP) administered into the middle ear. METHODS: An acute acoustic trauma was performed to 13 guinea pigs for a period of 1 h on Day -2. Two 2 days after the noise trauma, the animals were then assigned randomly to four experimental groups: control without gel, gel injection, gel-containing free DexP, gel-containing DexP loaded into liposomes. Auditory thresholds were measured with Auditory Brainstem Response before Day -2 and at Day 0, Day 7 and Day 30 after noise trauma. RESULTS: Seven days after, a complete hearing recovery was observed in the control group at all frequencies apart from 8 kHz, and no recovery was observed in the three groups receiving a gel injection. Thirty days after trauma, all of the animals had recovered normal hearing, apart from at the 8-kHz frequency, with similar auditory thresholds. CONCLUSIONS: Local DexP administration 48 h after a mild acoustic trauma did not improve hearing recovery, even with a sustained release in a specific gel formulation designed for inner ear therapy.

Robust Neuronal Discrimination in Primary Auditory Cortex Despite Degradations of Spectro-temporal Acoustic Details: Comparison Between Guinea Pigs with Normal Hearing and Mild Age-Related Hearing Loss.

This study investigated to which extent the primary auditory cortex of young normal-hearing and mild hearing-impaired aged animals is able to maintain invariant representation of critical temporal-modulation features when sounds are submitted to degradations of fine spectro-temporal acoustic details. This was achieved by recording ensemble of cortical responses to conspecific vocalizations in guinea pigs with either normal hearing or mild age-related sensorineural hearing loss. The vocalizations were degraded using a tone vocoder. The neuronal responses and their discrimination capacities (estimated by mutual information) were analyzed at single recording and population levels. For normal-hearing animals, the neuronal responses decreased as a function of the number of the vocoder frequency bands, so did their discriminative capacities at the single recording level. However, small neuronal populations were found to be robust to the degradations induced by the vocoder. Similar robustness was obtained when broadband noise was added to exacerbate further the spectro-temporal distortions produced by the vocoder. A comparable pattern of robustness to degradations in fine spectro-temporal details was found for hearing-impaired animals. However, the latter showed an overall decrease in neuronal discrimination capacities between vocalizations in noisy conditions. Consistent with previous studies, these results demonstrate that the primary auditory cortex maintains robust neural representation of temporal envelope features for communication sounds under a large range of spectro-temporal degradations.