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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.
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Distrofina , Ratones Noqueados , Conducta Social , Animales , Distrofina/genética , Distrofina/deficiencia , Ratones , Masculino , Emociones/fisiología , Miedo/fisiología , Miedo/psicología , Conducta Animal/fisiología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Ansiedad/genética , Ansiedad/psicologíaRESUMEN
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.
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Corteza Auditiva , Percepción Auditiva , Humanos , Ratones , Animales , Cobayas , Estimulación Acústica/métodos , Percepción Auditiva/fisiología , Ruido , Sonido , Corteza Auditiva/fisiologíaRESUMEN
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.
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Oído Interno , Potenciales Evocados Auditivos del Tronco Encefálico , Ratones , Humanos , Animales , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Oído Interno/diagnóstico por imagenRESUMEN
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.
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Pérdida Auditiva Provocada por Ruido , Animales , Percepción Auditiva , Umbral Auditivo , Cóclea , Potenciales Evocados Auditivos del Tronco Encefálico , Humanos , RatasRESUMEN
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.
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Comunicación Animal , Percepción Auditiva/fisiología , Discriminación en Psicología/fisiología , Ruido , Vocalización Animal/fisiología , Estimulación Acústica , Algoritmos , Animales , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Femenino , Cobayas , Masculino , Enmascaramiento Perceptual , Relación Señal-Ruido , Colículos Superiores/citología , Colículos Superiores/fisiología , Tálamo/citología , Tálamo/fisiologíaRESUMEN
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.
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Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Vocalización Animal/fisiología , Animales , Vías Auditivas/fisiología , Pinzones , MasculinoRESUMEN
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.
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Corteza Auditiva , Estimulación Acústica , Ruido , Reproducibilidad de los Resultados , SonidoRESUMEN
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.
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ADP-Ribosil Ciclasa 1/genética , ADP-Ribosil Ciclasa 1/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Plasticidad Neuronal , Corteza Prefrontal/fisiopatología , Aminas/metabolismo , Animales , Ansiedad , Trastorno del Espectro Autista/genética , Conducta Animal , Tronco Encefálico , Calcio/metabolismo , Miedo , Regulación de la Expresión Génica , Genotipo , Imagen por Resonancia Magnética , Masculino , Aprendizaje por Laberinto , Megalencefalia/fisiopatología , Memoria , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oxitocina/sangre , Polimorfismo de Nucleótido Simple , Reflejo de Sobresalto , Factores de Riesgo , Conducta SocialRESUMEN
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.
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Estimulación Acústica/efectos adversos , Corteza Auditiva/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Ruido/efectos adversos , Estimulación Acústica/tendencias , Envejecimiento/fisiología , Animales , Corteza Auditiva/patología , Humanos , Factores de TiempoRESUMEN
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.
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Encéfalo , Metáfora , Cognición , MasculinoRESUMEN
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.
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Cognición/fisiología , Norepinefrina/fisiología , Encéfalo/fisiología , HumanosRESUMEN
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 ß 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 ß 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.
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Comunicación Animal , Corteza Auditiva/fisiología , Norepinefrina/farmacología , Estimulación Acústica , Agonistas Adrenérgicos/farmacología , Animales , Discriminación en Psicología , Femenino , Cobayas , Masculino , SonidoRESUMEN
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.
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Percepción Auditiva/fisiología , Encéfalo/fisiopatología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/fisiopatología , Distrofina/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatología , Distrofia Muscular de Duchenne/psicología , Filtrado Sensorial/fisiología , Estimulación Acústica , Animales , Reacción de Prevención/fisiología , Conducta Animal/fisiología , Encéfalo/metabolismo , Condicionamiento Clásico/fisiología , Modelos Animales de Enfermedad , Distrofina/genética , Potenciales Evocados Auditivos del Tronco Encefálico , Función Ejecutiva/fisiología , Miedo/fisiología , Aprendizaje por Laberinto/fisiología , Memoria a Largo Plazo/fisiología , Memoria a Corto Plazo/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Reflejo de Sobresalto , Memoria Espacial/fisiología , Navegación Espacial/fisiologíaRESUMEN
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.
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Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Neuronas/fisiología , Estimulación Acústica/métodos , Animales , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Cobayas , Microelectrodos , Ratas Sprague-Dawley , Espectrografía del Sonido , Especificidad de la EspecieRESUMEN
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.
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Comunicación Animal , Corteza Auditiva/fisiología , Corteza Cerebral/fisiología , Vocalización Animal/fisiología , Algoritmos , Animales , Corteza Auditiva/citología , Percepción Auditiva/fisiología , Baclofeno/análogos & derivados , Baclofeno/farmacología , Mapeo Encefálico , Discriminación en Psicología/fisiología , Fenómenos Electrofisiológicos , Espacio Extracelular , Femenino , Antagonistas del GABA/farmacología , Cobayas , Masculino , Microinyecciones , Neuronas/fisiología , Técnicas de Placa-Clamp , Ácidos Fosfínicos/farmacología , Propanolaminas/farmacología , Piridazinas/farmacología , Receptores de GABA-A/efectos de los fármacos , Receptores de GABA-B/efectos de los fármacosRESUMEN
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.
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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.
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Corteza Auditiva/fisiología , Percepción Auditiva/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología , Animales , Cobayas , Análisis de Componente PrincipalRESUMEN
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.
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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.
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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.