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Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here.

Background: The Duchenne and Becker muscular dystrophies (DMD, BMD) are neuromuscular disorders commonly associated with diverse cognitive and behavioral comorbidities. Genotype-phenotype studies suggest that severity and risk of central defects in DMD patients increase with cumulative loss of different dystrophins produced in CNS from independent promoters of the DMD gene. Mutations affecting all dystrophins are nevertheless rare and therefore the clinical evidence on the contribution of the shortest Dp71 isoform to cognitive and behavioral dysfunctions is limited. In this study, we evaluated social, emotional and locomotor functions, and fear-related learning in the Dp71-null mouse model specifically lacking this short dystrophin., Results: We demonstrate the presence of abnormal social behavior and ultrasonic vocalization in Dp71-null mice, accompanied by slight changes in exploratory activity and anxiety-related behaviors, in the absence of myopathy and alterations of learning and memory of aversive cue-outcome associations., Conclusions: These results support the hypothesis that distal DMD gene mutations affecting Dp71 may contribute to the emergence of social and emotional problems that may relate to the autistic traits and executive dysfunctions reported in DMD. The present alterations in Dp71-null mice may possibly add to the subtle social behavior problems previously associated with the loss of the Dp427 dystrophin, in line with the current hypothesis that risk and severity of behavioral problems in patients increase with cumulative loss of several brain dystrophin isoforms., (© 2024. The Author(s).)

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea. The present study characterized the impact of changing electrical pulse shapes from the standard biphasic symmetric to the asymmetrical shape by quantifying the evoked firing rate and the spatial activation in the guinea pig primary auditory cortex (A1). At a fixed charge, the firing rate and the spatial activation in A1 decreased by 15 to 25 % when asymmetric pulses were used to activate the auditory nerve fibers, suggesting a potential reduction of the spread of excitation inside the cochlea. A strong "polarity-order" effect was found as the reduction was more pronounced when the first phase of the pulse was cathodic with high amplitude. These results suggest that the use of asymmetrical pulse shapes in clinical settings can potentially reduce the channel interactions in CI users., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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.

Purpose: Assess short-term and long-term effects of chronic exposure to an ultrahigh static magnetic (B 0 ) 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 B 0 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 B 0 . 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 B 0 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 B 0 exposure., Conclusion: Despite the transient disturbance of mice vestibular system observed immediately after B 0 exposure, no short-term nor long-term alteration was detected with behavioral and ABR tests., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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.

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., (© 2022 The Authors. The Journal of Physiology © 2022 The Physiological Society.)

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.

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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2022. The Author(s).)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Souffi, Nodal, Bajo and Edeline.)

Background noise strongly penalizes auditory perception of speech in humans or vocalizations in animals. Despite this, auditory neurons are still able to detect communications sounds against considerable levels of background noise. We collected neuronal recordings in cochlear nucleus (CN), inferior colliculus (IC), auditory thalamus, and primary and secondary auditory cortex in response to vocalizations presented either against a stationary or a chorus noise in anesthetized guinea pigs at three signal-to-noise ratios (SNRs; -10, 0, and 10 dB). We provide evidence that, at each level of the auditory system, five behaviors in noise exist within a continuum, from neurons with high-fidelity representations of the signal, mostly found in IC and thalamus, to neurons with high-fidelity representations of the noise, mostly found in CN for the stationary noise and in similar proportions in each structure for the chorus noise. The two cortical areas displayed fewer robust responses than the IC and thalamus. Furthermore, between 21% and 72% of the neurons (depending on the structure) switch categories from one background noise to another, even if the initial assignment of these neurons to a category was confirmed by a severe bootstrap procedure. Importantly, supervised learning pointed out that assigning a recording to one of the five categories can be predicted up to a maximum of 70% based on both the response to signal alone and noise alone., (Copyright © 2021 Souffi et al.)

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., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

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., (© 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.)

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., (Copyright © 2020 the authors.)

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 hSOD1 G93A 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 hSOD1 G93A 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.

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.

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., (Copyright © 2019 the authors.)

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 Ca 2+ -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.

Aging is often considered to affect both the peripheral (i.e. the cochlea) and central (brainstem and thalamus-cortex) auditory systems. We investigated the effects of aging on the cochlea, brainstem and cortex of female Sprague-Dawley rats. The auditory nerve threshold remained stable between the ages of nine and 21 months, as did distortion product otoacoustic emissions and the number of ribbon synapses between inner hair cells and nerve fibers. The first clear signs of aging appeared in the brainstem, in which response amplitude decreased, with thresholds remaining stable until the age of 15 months, and increasing slightly thereafter. The responses of primary auditory cortex neurons revealed specific effects of aging: at 21 months, receptive fields were spectrally narrower and the temporal reliability of responses to communication sounds was lower. However, aging had a null or even positive effect on neuronal responses in the presence of background noise, responses to amplitude-modulated sounds, and responses in gap-detection protocols. Overall, inter-animal variability remained high relative to the variability across groups of different ages, for all parameters tested. Behavioral performance for the modulation depth of amplitude modulation noise was worse in 21-month old animals than in other animals. Age-related alterations of cortical and behavioral responses were thus observed in animals displaying no signs of aging at the peripheral level. These results suggest that intrinsic, central aging effects can affect the perception of acoustic stimuli independently of the effects of aging on peripheral receptors., (Copyright © 2019. Published by Elsevier Ltd.)

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., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Oticon Medical only provided some of the research material in the sole purpose of helping setting-up the experiment. The authors have no competing interests relating to employment, consultancy, patents, products in development or marketed products. PS provided help in the editing of the article based on his expertise in the research field to avoid errors and inaccuracies. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

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.

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.

Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1ß (IL1ß) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1ß mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

Learning by imitation involves not only perceiving another individual's action to copy it, but also the formation of a memory trace in order to gradually establish a correspondence between the sensory and motor codes, which represent this action through sensorimotor experience. Memory and sensorimotor processes are closely intertwined. Mirror neurons, which fire both when the same action is performed or perceived, have received considerable attention in the context of imitation. An influential view of memory processes considers that the consolidation of newly acquired information or skills involves an active offline reprocessing of memories during sleep within the neuronal networks that were initially used for encoding. Here, we review the recent advances in the field of mirror neurons and offline processes in the songbird. We further propose a theoretical framework that could establish the neurobiological foundations of sensorimotor learning by imitation. We propose that the reactivation of neuronal assemblies during offline periods contributes to the integration of sensory feedback information and the establishment of sensorimotor mirroring activity at the neuronal level., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The timbre of a sound plays an important role in our ability to discriminate between behaviorally relevant auditory categories, such as different vowels in speech. Here, we investigated, in the primary auditory cortex (A1) of anesthetized guinea pigs, the neural representation of vowels with impoverished timbre cues. Five different vowels were presented with durations ranging from 2 to 128 ms. A psychophysical experiment involving human listeners showed that identification performance was near ceiling for the longer durations and degraded close to chance level for the shortest durations. This was likely due to spectral splatter, which reduced the contrast between the spectral profiles of the vowels at short durations. Effects of vowel duration on cortical responses were well predicted by the linear frequency responses of A1 neurons. Using mutual information, we found that auditory cortical neurons in the guinea pig could be used to reliably identify several vowels for all durations. Information carried by each cortical site was low on average, but the population code was accurate even for durations where human behavioral performance was poor. These results suggest that a place population code is available at the level of A1 to encode spectral profile cues for even very short sounds., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Mather and colleagues' arguments require rethinking at the mechanistic level. The arguments on the physiological effects of norepinephrine at the cortical level are inconsistent with large parts of the literature. There is no evidence that norepinephrine induces local "hotspots": Norepinephrine mainly decreases evoked responses; facilitating effects are rare and not localized. More generally, the idea that perception benefits from "local hotspots" is hardly compatible with the fact that neural representations involve largely distributed activation of cortical and subcortical networks.

Duchenne muscular dystrophy (DMD) is associated with language disabilities and deficits in learning and memory, leading to intellectual disability in a patient subpopulation. Recent studies suggest the presence of broader deficits affecting information processing, short-term memory and executive functions. While the absence of the full-length dystrophin (Dp427) is a common feature in all patients, variable mutation profiles may additionally alter distinct dystrophin-gene products encoded by separate promoters. However, the nature of the cognitive dysfunctions specifically associated with the loss of distinct brain dystrophins is unclear. Here we show that the loss of the full-length brain dystrophin in mdx mice does not modify the perception and sensorimotor gating of auditory inputs, as assessed using auditory brainstem recordings and prepulse inhibition of startle reflex. In contrast, both acquisition and long-term retention of cued and trace fear memories were impaired in mdx mice, suggesting alteration in a functional circuit including the amygdala. Spatial learning in the water maze revealed reduced path efficiency, suggesting qualitative alteration in mdx mice learning strategy. However, spatial working memory performance and cognitive flexibility challenged in various behavioral paradigms in water and radial-arm mazes were unimpaired. The full-length brain dystrophin therefore appears to play a role during acquisition of associative learning as well as in general processes involved in memory consolidation, but no overt involvement in working memory and/or executive functions could be demonstrated in spatial learning tasks., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The functional properties of auditory cortex neurons are most often investigated separately, through spectrotemporal receptive fields (STRFs) for the frequency tuning and the use of frequency sweeps sounds for selectivity to velocity and direction. In fact, auditory neurons are sensitive to a multidimensional space of acoustic parameters where spectral, temporal and spatial dimensions interact. We designed a multi-parameter stimulus, the random double sweep (RDS), composed of two uncorrelated random sweeps, which gives an easy, fast and simultaneous access to frequency tuning as well as frequency modulation sweep direction and velocity selectivity, frequency interactions and temporal properties of neurons. Reverse correlation techniques applied to recordings from the primary auditory cortex of guinea pigs and rats in response to RDS stimulation revealed the variety of temporal dynamics of acoustic patterns evoking an enhanced or suppressed firing rate. Group results on these two species revealed less frequent suppression areas in frequency tuning STRFs, the absence of downward sweep selectivity, and lower phase locking abilities in the auditory cortex of rats compared to guinea pigs.

Key Points: Many studies have described the action of Noradrenaline (NA) on the properties of cortical receptive fields, but none has assessed how NA affects the discrimination abilities of cortical cells between natural stimuli. In the present study, we compared the consequences of NA topical application on spectro-temporal receptive fields (STRFs) and responses to communication sounds in the primary auditory cortex. NA application reduced the STRFs (an effect replicated by the alpha1 agonist Phenylephrine) but did not change, on average, the responses to communication sounds. For cells exhibiting increased evoked responses during NA application, the discrimination abilities were enhanced as quantified by Mutual Information. The changes induced by NA on parameters extracted from the STRFs and from responses to communication sounds were not related., Abstract: The alterations exerted by neuromodulators on neuronal selectivity have been the topic of a vast literature in the visual, somatosensory, auditory and olfactory cortices. However, very few studies have investigated to what extent the effects observed when testing these functional properties with artificial stimuli can be transferred to responses evoked by natural stimuli. Here, we tested the effect of noradrenaline (NA) application on the responses to pure tones and communication sounds in the guinea-pig primary auditory cortex. When pure tones were used to assess the spectro-temporal receptive field (STRF) of cortical cells, NA triggered a transient reduction of the STRFs in both the spectral and the temporal domain, an effect replicated by the α1 agonist phenylephrine whereas α2 and β agonists induced STRF expansion. When tested with communication sounds, NA application did not produce significant effects on the firing rate and spike timing reliability, despite the fact that α1, α2 and β agonists by themselves had significant effects on these measures. However, the cells whose evoked responses were increased by NA application displayed enhanced discriminative abilities. These cells had initially smaller STRFs than the rest of the population. A principal component analysis revealed that the variations of parameters extracted from the STRF and those extracted from the responses to natural stimuli were not correlated. These results suggest that probing the action of neuromodulators on cortical cells with artificial stimuli does not allow us to predict their action on responses to natural stimuli., (© 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.)

People are increasingly being exposed to environmental noise from traffic, media and other sources that falls within and outside legal limits. Although such environmental noise is known to cause stress in the auditory system, it is still generally considered to be harmless. This complacency may be misplaced: even in the absence of cochlear damage, new findings suggest that environmental noise may progressively degrade hearing through alterations in the way sound is represented in the adult auditory cortex.

Over the last decade, the consequences of acoustic trauma on the functional properties of auditory cortex neurons have received growing attention. Changes in spontaneous and evoked activity, shifts of characteristic frequency (CF), and map reorganizations have extensively been described in anesthetized animals (e.g., Noreña and Eggermont, 2003, 2005). Here, we examined how the functional properties of cortical cells are modified after partial hearing loss in awake guinea pigs. Single unit activity was chronically recorded in awake, restrained, guinea pigs from 3 days before up to 15 days after an acoustic trauma induced by a 5 kHz 110 dB tone delivered for 1 h. Auditory brainstem responses (ABRs) audiograms indicated that these parameters produced a mean ABR threshold shift of 20 dB SPL at, and one octave above, the trauma frequency. When tested with pure tones, cortical cells showed on average a 25 dB increase in threshold at CF the day following the trauma. Over days, this increase progressively stabilized at only 10 dB above control value indicating a progressive recovery of cortical thresholds, probably reflecting a progressive shift from temporary threshold shift (TTS) to permanent threshold shift (PTS). There was an increase in response latency and in response variability the day following the trauma but these parameters returned to control values within 3 days. When tested with conspecific vocalizations, cortical neurons also displayed an increase in response latency and in response duration the day after the acoustic trauma, but there was no effect on the average firing rate elicited by the vocalization. These findings suggest that, in cases of moderate hearing loss, the temporal precision of neuronal responses to natural stimuli is impaired despite the fact the firing rate showed little or no changes.

A major goal in auditory neuroscience is to characterize how communication sounds are represented at the cortical level. The present review aims at investigating the role of auditory cortex in the processing of speech, bird songs and other vocalizations, which all are spectrally and temporally highly structured sounds. Whereas earlier studies have simply looked for neurons exhibiting higher firing rates to particular conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determined the coding capacity of temporal spike patterns, which are prominent in primary and non-primary areas (and also in non-auditory cortical areas). In several cases, this information seems to be correlated with the behavioral performance of human or animal subjects, suggesting that spike-timing based coding strategies might set the foundations of our perceptive abilities. Also, it is now clear that the responses of auditory cortex neurons are highly nonlinear and that their responses to natural stimuli cannot be predicted from their responses to artificial stimuli such as moving ripples and broadband noises. Since auditory cortex neurons cannot follow rapid fluctuations of the vocalizations envelope, they only respond at specific time points during communication sounds, which can serve as temporal markers for integrating the temporal and spectral processing taking place at subcortical relays. Thus, the temporal sparse code of auditory cortex neurons can be considered as a first step for generating high level representations of communication sounds independent of the acoustic characteristic of these sounds. This article is part of a Special Issue entitled "Communication Sounds and the Brain: New Directions and Perspectives"., (Copyright © 2013 Elsevier B.V. All rights reserved.)

In social environments, choosing between multiple rewards is modulated by the uncertainty of the situation. Here, we compared how mice interact with a conspecific and how they use acoustic communication during this interaction in a three chambers task (no social threat was possible) and a Social Interaction Task, SIT (uncertain situation as two mice interact freely). We further manipulated the motivational state of the mice to see how they rank natural rewards such as social contact, food, and novelty seeking. We previously showed that beta2-subunit containing nicotinic receptors-β2(*)nAChRs- are required for establishing reward ranking between social interaction, novelty exploration, and food consumption in social situations with high uncertainty. Knockout mice for β2(*)nAChRs-β2(-/-)mice- exhibit profound impairment in making social flexible choices, as compared to control -WT- mice. Our current data shows that being confronted with a conspecific in a socially safe environment as compared to a more uncertain environment, drastically reduced communication between the two mice, and changed their way to deal with a social conspecific. Furthermore, we demonstrated for the first time, that β2(-/-) mice had the same motivational ranking than WT mice when placed in a socially safe environment. Therefore, β2(*)nAChRs are not necessary for integrating social information or social rewards per se, but are important for making choices, only in a socially uncertain environment. This seems particularly important in the context of Social Neuroscience, as numerous animal models are used to provide novel insights and to test promising novel treatments of human pathologies affecting social and communication processes, among which Autistic spectrum disorders and schizophrenia.

In all sensory modalities, intracortical inhibition shapes the functional properties of cortical neurons but also influences the responses to natural stimuli. Studies performed in various species have revealed that auditory cortex neurons respond to conspecific vocalizations by temporal spike patterns displaying a high trial-to-trial reliability, which might result from precise timing between excitation and inhibition. Studying the guinea pig auditory cortex, we show that partial blockage of GABAA receptors by gabazine (GBZ) application (10 μm, a concentration that promotes expansion of cortical receptive fields) increased the evoked firing rate and the spike-timing reliability during presentation of communication sounds (conspecific and heterospecific vocalizations), whereas GABAB receptor antagonists [10 μm saclofen; 10-50 μm CGP55845 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid)] had nonsignificant effects. Computing mutual information (MI) from the responses to vocalizations using either the evoked firing rate or the temporal spike patterns revealed that GBZ application increased the MI derived from the activity of single cortical site but did not change the MI derived from population activity. In addition, quantification of information redundancy showed that GBZ significantly increased redundancy at the population level. This result suggests that a potential role of intracortical inhibition is to reduce information redundancy during the processing of natural stimuli.

Local field potentials (LFPs) recorded in the auditory cortex of mammals are known to reveal weakly selective and often multimodal spectrotemporal receptive fields in contrast to spiking activity. This may in part reflect the wider "listening sphere" of LFPs relative to spikes due to the greater current spread at low than high frequencies. We recorded LFPs and spikes from auditory cortex of guinea pigs using 16-channel electrode arrays. LFPs were processed by a component analysis technique that produces optimally tuned linear combinations of electrode signals. Linear combinations of LFPs were found to have sharply tuned responses, closer to spike-related tuning. The existence of a sharply tuned component implies that a cortical neuron (or group of neurons) capable of forming a linear combination of its inputs has access to that information. Linear combinations of signals from electrode arrays reveal information latent in the subspace spanned by multichannel LFP recordings and are justified by the fact that the observations themselves are linear combinations of neural sources.

Over the last two decades, a vast literature has described the influence of neuromodulatory systems on the responses of sensory cortex neurons (review in Gu, 2002; Edeline, 2003; Weinberger, 2003; Metherate, 2004, 2011). At the single cell level, facilitation of evoked responses, increases in signal-to-noise ratio, and improved functional properties of sensory cortex neurons have been reported in the visual, auditory, and somatosensory modality. At the map level, massive cortical reorganizations have been described when repeated activation of a neuromodulatory system are associated with a particular sensory stimulus. In reviewing our knowledge concerning the way the noradrenergic and cholinergic system control sensory cortices, I will point out that the differences between the protocols used to reveal these effects most likely reflect different assumptions concerning the role of the neuromodulators. More importantly, a gap still exists between the descriptions of neuromodulatory effects and the concepts that are currently applied to decipher the neural code operating in sensory cortices. Key examples that bring this gap into focus are the concept of cell assemblies and the role played by the spike timing precision (i.e., by the temporal organization of spike trains at the millisecond time-scale) which are now recognized as essential in sensory physiology but are rarely considered in experiments describing the role of neuromodulators in sensory cortices. Thus, I will suggest that several lines of research, particularly in the field of computational neurosciences, should help us to go beyond traditional approaches and, ultimately, to understand how neuromodulators impact on the cortical mechanisms underlying our perceptual abilities.

Simultaneous recording of multiple neurons, or neuron groups, offers new promise for investigating fundamental questions about the neural code. We used arrays of 16 electrodes in the tonotopic, primary, auditory cortex of guinea pigs and we extracted LFP- and spike-based spectro-temporal receptive fields (STRFs). We confirm here that LFP signals provide broadly tuned activity which lacks frequency resolution compared to multiunit signals and, therefore, lead to large redundancy in neural responses even between recording sites far apart. Thanks to the use of multi-electrode arrays which allows simultaneous recordings, we also focused on functional relationships between neuronal discharges (through cross-correlations) and between LFPs (through coherence). Since the LFP is composed of distinct brain rhythms, the LFP results were split into three frequency bands from the slowest to the fastest components of LFPs. For driven as well as spontaneous activity, we show that components >70 Hz in LFPs are much less coherent between recording sites than slower components. In general, coherence between LFPs from two recordings sites is positively correlated with the degree of frequency overlap between the two corresponding STRFs, similar to cross-correlation between multiunit activities. However, coherence is only weakly correlated with cross-correlation in all frequency ranges. Altogether, these results suggest that LFPs reflect global functional connectivity in the thalamocortical auditory system whereas spiking activities reflect more independent local processing., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Spectro-temporal properties of auditory cortex neurons have been extensively studied with artificial sounds but it is still unclear whether they help in understanding neuronal responses to communication sounds. Here, we directly compared spectro-temporal receptive fields (STRFs) obtained from the same neurons using both artificial stimuli (dynamic moving ripples, DMRs) and natural stimuli (conspecific vocalizations) that were matched in terms of spectral content, average power and modulation spectrum. On a population of auditory cortex neurons exhibiting reliable tuning curves when tested with pure tones, significant STRFs were obtained for 62% of the cells with vocalizations and 68% with DMR. However, for many cells with significant vocalization-derived STRFs (STRF(voc)) and DMR-derived STRFs (STRF(dmr)), the BF, latency, bandwidth and global STRFs shape differed more than what would be predicted by spiking responses simulated by a linear model based on a non-homogenous Poisson process. Moreover STRF(voc) predicted neural responses to vocalizations more accurately than STRF(dmr) predicted neural response to DMRs, despite similar spike-timing reliability for both sets of stimuli. Cortical bursts, which potentially introduce nonlinearities in evoked responses, did not explain the differences between STRF(voc) and STRF(dmr). Altogether, these results suggest that the nonlinearity of auditory cortical responses makes it difficult to predict responses to communication sounds from STRFs computed from artificial stimuli.

Elderly people often show degraded hearing performance and have difficulties in understanding speech, particularly in noisy environments. Although loss in peripheral hearing sensitivity is an important factor in explaining these low performances, central alterations also have an impact but their exact contributions remained unclear. In this study, we focus on the functional effects of aging on auditory cortex responses. Neuronal discharges and local field potentials were recorded in the auditory cortex of aged guinea pigs (> 3 years), and several parameters characterizing the processing of auditory information were quantified: the acoustic thresholds, response strength, latency and duration of the response, and breadth of tuning. Several of these parameters were also quantified from auditory brainstem responses collected from the same animals, and recordings obtained from a population of animals with trauma-induced hearing loss were also included in this study. The results showed that aging and acoustic trauma reduced the response strength at both brainstem and cortical levels, and increased the response latencies more at the cortical level than at the brainstem level. In addition to the brainstem hearing loss, aging induced a 'cortical hearing loss' as judged by additive changes in the threshold and frequency response seen in the cortex. It also increased the duration of neural responses and reduced the receptive field bandwidth, effects that were not found in traumatized animals. These effects substantiate the notion that presbycusis involves both peripheral hearing loss and biological aging in the central auditory system., (© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

The increasing use of mobile phones by children raise issues about the effects of electromagnetic fields (EMF) on the immature Central Nervous System (CNS). In the present study, we quantified cell stress and glial responses in the brain of developing rats one day after a single exposure of 2 h to a GSM 1,800 MHz signal at a brain average Specific Absorption Rate (SAR) in the range of 1.7 to 2.5 W/kg. Young rats, exposed to EMF on postnatal days (P) 5 (n = 6), 15 (n = 5) or 35 (n = 6), were compared to pseudo-exposed littermate rats (n = 6 at all ages). We used western blotting to detect heat shock proteins (HSPs) and cytoskeleton- or neurotransmission-related proteins in the developing astroglia. The GSM signal had no significant effect on the abundance of HSP60, HSC70 or HSP90, of serine racemase, glutamate transporters including GLT1 and GLAST, or of glial fibrillary acid protein (GFAP) in either total or soluble tissue extracts. Imunohistochemical detection of CD68 antigen in brain sections from pseudo-exposed and exposed animals did not reveal any differences in the morphology or distribution of microglial cells. These results provide no evidence for acute cell stress or glial reactions indicative of early neural cell damage, in developing brains exposed to 1,800 MHz signals in the range of SAR used in our study.

Neurons in primary sensory cortices display selective receptive field plasticity in behavioral situations ranging from classical conditioning to attentional tasks, and it is generally assumed that neuromodulators promote this plasticity. Studies have shown that pairing a pure-tone and a stimulation of the nucleus basalis magnocellularis mimics the selective receptive field facilitations described after classical conditioning. Here, we evaluated the consequences of repeated pairings between a particular sound frequency and a phasic stimulation of locus coeruleus (LC) on the frequency tuning of auditory thalamus and auditory cortex neurons. Selective alterations for the paired frequency were observed for more than 30% of the cells recorded both in cortex and in thalamus. There were as much selective increases as selective decreases at the cortical level, whereas selective increases were prevailing at the thalamic level. Selective changes usually persisted 15 min after pairing in cortex; they dissipated in thalamus, and so did the general increases in both structures. In animals with stimulation sites outside the LC, pairing induced either general changes or no effect. These results indicate that the selective plasticity induced in the frequency tuning of auditory cortex neurons by LC stimulation is bidirectional, thereby suggesting that noradrenergic activation can contribute to the different forms of plasticity observed after distinct behavioral paradigms., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Over the last 15 years, an increasing number of studies have described the responsiveness of thalamic and cortical neurons to communication sounds. Whereas initial studies have simply looked for neurons exhibiting higher firing rate to conspecific vocalizations over their modified, artificially synthesized versions, more recent studies determine the relative contribution of "rate coding" and "temporal coding" to the information transmitted by spike trains. In this article, we aim at reviewing the different strategies employed by thalamic and cortical neurons to encode information about acoustic stimuli, from artificial to natural sounds. Considering data obtained with simple stimuli, we first illustrate that different facets of temporal code, ranging from a strict correspondence between spike-timing and stimulus temporal features to more complex coding strategies, do already exist with artificial stimuli. We then review lines of evidence indicating that spike-timing provides an efficient code for discriminating communication sounds from thalamus, primary and non-primary auditory cortex up to frontal areas. As the neural code probably developed, and became specialized, over evolution to allow precise and reliable processing of sounds that are of survival value, we argue that spike-timing based coding strategies might set the foundations of our perceptive abilities., (© 2010 Elsevier B.V. All rights reserved.)

Communication sounds exhibit temporal envelope fluctuations in the low frequency range (<70 Hz) and human speech has prominent 2-16 Hz modulations with a maximum at 3-4 Hz. Here, we propose a new phenomenological model of the human auditory pathway (from cochlea to primary auditory cortex) to simulate responses to amplitude-modulated white noise. To validate the model, performance was estimated by quantifying temporal modulation transfer functions (TMTFs). Previous models considered either the lower stages of the auditory system (up to the inferior colliculus) or only the thalamocortical loop. The present model, divided in two stages, is based on anatomical and physiological findings and includes the entire auditory pathway. The first stage, from the outer ear to the colliculus, incorporates inhibitory interneurons in the cochlear nucleus to increase performance at high stimuli levels. The second stage takes into account the anatomical connections of the thalamocortical system and includes the fast and slow excitatory and inhibitory currents. After optimizing the parameters of the model to reproduce the diversity of TMTFs obtained from human subjects, a patient-specific model was derived and the parameters were optimized to effectively reproduce both spontaneous activity and the oscillatory part of the evoked response., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Thresholds of auditory brainstem responses (ABRs) are widely used to estimate the level of noise-induced hearing loss or the level of acquired resistance to acoustic trauma after repeated exposures, i.e., the "toughening" effect. Less is known about ABR latencies and their relation to threshold changes. Guinea pigs were exposed to a traumatic pure tone at 5 kHz, 120 dB SPL, as either single (2 h, 4 h) or repeated (1 h every 48 h, four times) sessions. Thresholds and latencies of ABRs were monitored up to 45 days following the acoustic trauma. We show that latencies are prolonged in the case of large temporary threshold shifts observed in the days following trauma. The latency shift decreases after several repeated exposures, then stabilizes, similar to thresholds, suggesting that the "toughening" effect also applies to latencies. Permanent latency shift is usually very small compared to the permanent threshold shift. This effect could produce a recovery in the ability to process auditory information through the precise timing of neuronal events. Our study indicates that when estimated at suprathreshold stimulation level (70 dB SPL), latency provides complementary information to the sole threshold.

Understanding how communication sounds are processed and encoded in the central auditory system is critical to understanding the neural bases of acoustic communication. Here, we examined neuronal representations of species-specific vocalizations, which are communication sounds that many species rely on for survival and social interaction. In some species, the evoked responses of auditory cortex neurons are stronger in response to natural conspecific vocalizations than to their time-reversed, spectrally identical, counterparts. We applied information theory-based analyses to single-unit spike trains collected in the auditory cortex (n = 139) and auditory thalamus (n = 135) of anesthetized animals as well as in the auditory cortex (n = 119) of awake guinea pigs during presentation of four conspecific vocalizations. Few thalamic and cortical cells (<10%) displayed a firing rate preference for the natural version of these vocalizations. In contrast, when the information transmitted by the spike trains was quantified with a temporal precision of 10-50 ms, many cells (>75%) displayed a significant amount of information (i.e., >2SD above chance levels), especially in the awake condition. The computed correlation index between spike trains (R(corr), defined by Schreiber et al., 2003) indicated similar spike-timing reliability for both the natural and time-reversed versions of each vocalization, but higher reliability for awake animals compared with anesthetized animals. Based on temporal discharge patterns, even cells that were only weakly responsive to vocalizations displayed a significant level of information. These findings emphasize the importance of temporal discharge patterns as a coding mechanism for natural communication sounds, particularly in awake animals.