RESUMEN
Novel stimulation methods are needed to overcome the limitations of contemporary cochlear implants. Optogenetics is a technique that confers light sensitivity to neurons via the genetic introduction of light-sensitive ion channels. By controlling neural activity with light, auditory neurons can be activated with higher spatial precision. Understanding the behaviour of opsins at high stimulation rates is an important step towards their translation. To elucidate this, we compared the temporal characteristics of auditory nerve and inferior colliculus responses to optogenetic, electrical, and combined optogenetic-electrical stimulation in virally transduced mice expressing one of two channelrhodopsins, ChR2-H134R or ChIEF, at stimulation rates up to 400 pulses per second (pps). At 100 pps, optogenetic responses in ChIEF mice demonstrated higher fidelity, less change in latency, and greater response stability compared to responses in ChR2-H134R mice, but not at higher rates. Combined stimulation improved the response characteristics in both cohorts at 400 pps, although there was no consistent facilitation of electrical responses. Despite these results, day-long stimulation (up to 13 h) led to severe and non-recoverable deterioration of the optogenetic responses. The results of this study have significant implications for the translation of optogenetic-only and combined stimulation techniques for hearing loss.
Asunto(s)
Vías Auditivas , Channelrhodopsins , Estimulación Eléctrica , Optogenética , Animales , Optogenética/métodos , Ratones , Vías Auditivas/fisiología , Vías Auditivas/metabolismo , Channelrhodopsins/metabolismo , Channelrhodopsins/genética , Estimulación Eléctrica/métodos , Colículos Inferiores/fisiología , Colículos Inferiores/metabolismo , Nervio Coclear/fisiología , Nervio Coclear/metabolismo , Cinética , Implantes CoclearesRESUMEN
The detection of novel, low probability events in the environment is critical for survival. To perform this vital task, our brain is continuously building and updating a model of the outside world; an extensively studied phenomenon commonly referred to as predictive coding. Predictive coding posits that the brain is continuously extracting regularities from the environment to generate predictions. These predictions are then used to supress neuronal responses to redundant information, filtering those inputs, which then automatically enhances the remaining, unexpected inputs. We have recently described the ability of auditory neurons to generate predictions about expected sensory inputs by detecting their absence in an oddball paradigm using omitted tones as deviants. Here, we studied the responses of individual neurons to omitted tones by presenting individual sequences of repetitive pure tones, using both random and periodic omissions, presented at both fast and slow rates in the inferior colliculus and auditory cortex neurons of anesthetized rats. Our goal was to determine whether feature-specific dependence of these predictions exists. Results showed that omitted tones could be detected at both high (8 Hz) and slow repetition rates (2 Hz), with detection being more robust at the non-lemniscal auditory pathway.
Asunto(s)
Estimulación Acústica , Corteza Auditiva , Vías Auditivas , Colículos Inferiores , Animales , Corteza Auditiva/fisiología , Colículos Inferiores/fisiología , Vías Auditivas/fisiología , Masculino , Percepción Auditiva/fisiología , Ratas , Anestesia , Neuronas/fisiología , Ratas Sprague-Dawley , Factores de Tiempo , Potenciales Evocados AuditivosRESUMEN
A speech intelligibility (SI) prediction model is proposed that includes an auditory preprocessing component based on the physiological anatomy and activity of the human ear, a hierarchical spiking neural network, and a decision back-end processing based on correlation analysis. The auditory preprocessing component effectively captures advanced physiological details of the auditory system, such as retrograde traveling waves, longitudinal coupling, and cochlear nonlinearity. The ability of the model to predict data from normal-hearing listeners under various additive noise conditions was considered. The predictions closely matched the experimental test data under all conditions. Furthermore, we developed a lumped mass model of a McGee stainless-steel piston with the middle-ear to study the recovery of individuals with otosclerosis. We show that the proposed SI model accurately simulates the effect of middle-ear intervention on SI. Consequently, the model establishes a model-based relationship between objective measures of human ear damage, like distortion product otoacoustic emissions, and speech perception. Moreover, the SI model can serve as a robust tool for optimizing parameters and for preoperative assessment of artificial stimuli, providing a valuable reference for clinical treatments of conductive hearing loss.
Asunto(s)
Redes Neurales de la Computación , Inteligibilidad del Habla , Percepción del Habla , Humanos , Percepción del Habla/fisiología , Estimulación Acústica , Oído Medio/fisiología , Ruido/efectos adversos , Emisiones Otoacústicas Espontáneas , Otosclerosis/fisiopatología , Otosclerosis/cirugía , Simulación por Computador , Vías Auditivas/fisiología , Cóclea/fisiologíaRESUMEN
The binaural interaction component (BIC) of the auditory evoked potential is the difference between the waveforms of the binaural response and the sum of left and right monaural responses. This investigation examined BICs of the auditory brainstem (ABR) and middle-latency (MLR) responses concerning three objectives: 1) the level of the auditory system at which low-frequency dominance in BIC amplitudes begins when the binaural temporal fine structure is more influential with lower- than higher-frequency content; 2) how BICs vary as a function of frequency and lateralization predictability, as could relate to the improved lateralization of high-frequency sounds; 3) how attention affects BICs. Sixteen right-handed participants were presented with either low-passed (< 1000 Hz) or high-passed (> 2000 Hz) clicks at 30 dB SL with a 38 dB (A) masking noise, at a stimulus onset asynchrony of 180 ms. Further, this repeated-measures design manipulated stimulus presentation (binaural, left monaural, right monaural), lateralization predictability (unpredictable, predictable), and attended modality (either auditory or visual). For the objectives, respectively, the results were: 1) whereas low-frequency dominance in BIC amplitudes began during, and continued after, the Na-BIC, binaural (center) as well as summed monaural (left and right) amplitudes revealed low-frequency dominance only after the Na wave; 2) with a predictable position that was fixed, no BIC exhibited equivalent amplitudes between low- and high-passed clicks; 3) whether clicks were low- or high-passed, selective attention affected the ABR-BIC yet not MLR-BICs. These findings indicate that low-frequency dominance in lateralization begins at the Na latency, being independent of the efferent cortico-collicular pathway's influence.
Asunto(s)
Estimulación Acústica , Atención , Potenciales Evocados Auditivos del Tronco Encefálico , Lateralidad Funcional , Tiempo de Reacción , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Atención/fisiología , Tronco Encefálico/fisiología , Vías Auditivas/fisiología , Factores de Tiempo , Electroencefalografía , Enmascaramiento Perceptual , Estimulación Luminosa , Percepción Auditiva/fisiología , Umbral AuditivoRESUMEN
BACKGROUND: In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. METHODS AND PARTICIPANTS: The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (the P2m response, measured using magnetoencephalography, MEG) in a cross-sectional (N = 47, 2 to 24 months, 19 females) as well as longitudinal cohort (N = 18, 2 to 29 months, 8 females) of typically developing infants and toddlers. Of 18 longitudinal infants, 2 infants had data from 3 timepoints and 16 infants had data from 2 timepoints. RESULTS: In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. Auditory radiation diffusion accounted for significant variance in P2m latency, even after removing the variance associated with age in both P2m latency and auditory radiation diffusion measures. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. CONCLUSIONS: Findings provide strong support for the hypothesis that an increase in thalamocortical neural conduction velocity, due to increased axon diameter and/or myelin maturation, contributes to a decrease in the infant P2m auditory evoked response latency. SIGNIFICANCE: Infant multimodal brain imaging identifies brain mechanisms contributing to the rapid changes in neural circuit activity during the first two years of life.
Asunto(s)
Corteza Auditiva , Potenciales Evocados Auditivos , Magnetoencefalografía , Humanos , Femenino , Masculino , Lactante , Corteza Auditiva/crecimiento & desarrollo , Corteza Auditiva/diagnóstico por imagen , Corteza Auditiva/fisiología , Potenciales Evocados Auditivos/fisiología , Preescolar , Magnetoencefalografía/métodos , Estudios Transversales , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Estudios Longitudinales , Vías Auditivas/crecimiento & desarrollo , Vías Auditivas/diagnóstico por imagen , Vías Auditivas/fisiología , Estimulación AcústicaRESUMEN
Auditory space has been conceptualized as a matrix of systematically arranged combinations of binaural disparity cues that arise in the superior olivary complex (SOC). The computational code for interaural time and intensity differences utilizes excitatory and inhibitory projections that converge in the inferior colliculus (IC). The challenge is to determine the neural circuits underlying this convergence and to model how the binaural cues encode location. It has been shown that midbrain neurons are largely excited by sound from the contralateral ear and inhibited by sound leading at the ipsilateral ear. In this context, ascending projections from the lateral superior olive (LSO) to the IC have been reported to be ipsilaterally glycinergic and contralaterally glutamatergic. This study used CBA/CaH mice (3-6 months old) and applied unilateral retrograde tracing techniques into the IC in conjunction with immunocytochemical methods with glycine and glutamate transporters (GlyT2 and vGLUT2, respectively) to analyze the projection patterns from the LSO to the IC. Glycinergic and glutamatergic neurons were spatially intermixed within the LSO, and both types projected to the IC. For GlyT2 and vGLUT2 neurons, the average percentage of ipsilaterally and contralaterally projecting cells was similar (ANOVA, p = 0.48). A roughly equal number of GlyT2 and vGLUT2 neurons did not project to the IC. The somatic size and shape of these neurons match the descriptions of LSO principal cells. A minor but distinct population of small (< 40 µm2) neurons that labeled for GlyT2 did not project to the IC; these cells emerge as candidates for inhibitory local circuit neurons. Our findings indicate a symmetric and bilateral projection of glycine and glutamate neurons from the LSO to the IC. The differences between our results and those from previous studies suggest that species and habitat differences have a significant role in mechanisms of binaural processing and highlight the importance of research methods and comparative neuroscience. These data will be important for modeling how excitatory and inhibitory systems converge to create auditory space in the CBA/CaH mouse.
Asunto(s)
Vías Auditivas , Ácido Glutámico , Proteínas de Transporte de Glicina en la Membrana Plasmática , Glicina , Colículos Inferiores , Ratones Endogámicos CBA , Complejo Olivar Superior , Animales , Glicina/metabolismo , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Ratones , Colículos Inferiores/fisiología , Colículos Inferiores/metabolismo , Colículos Inferiores/citología , Vías Auditivas/fisiología , Vías Auditivas/metabolismo , Ácido Glutámico/metabolismo , Complejo Olivar Superior/fisiología , Complejo Olivar Superior/metabolismo , Masculino , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Neuronas/metabolismo , Neuronas/fisiologíaRESUMEN
The numerical sense of animals includes identifying the numerosity of a sequence of events that occur with specific intervals, e.g., notes in a call or bar of music. Across nervous systems, the temporal patterning of spikes can code these events, but how this information is decoded (counted) remains elusive. In the anuran auditory system, temporal information of this type is decoded in the midbrain, where "interval-counting" neurons spike only after at least a threshold number of sound pulses have occurred with specific timing. We show that this decoding process, i.e., interval counting, arises from integrating phasic, onset-type and offset inhibition with excitation that augments across successive intervals, possibly due to a progressive decrease in "shunting" effects of inhibition. Because these physiological properties are ubiquitous within and across central nervous systems, interval counting may be a general mechanism for decoding diverse information coded/encoded in temporal patterns of spikes, including "bursts," and estimating elapsed time.
Asunto(s)
Neuronas , Animales , Neuronas/fisiología , Percepción Auditiva/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Modelos Neurológicos , Vías Auditivas/fisiología , Factores de TiempoRESUMEN
The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.
Asunto(s)
Estimulación Acústica , Audiometría de Respuesta Evocada , Vías Auditivas , Chinchilla , Nervio Coclear , Estimulación Luminosa , Vigilia , Tecnología Inalámbrica , Animales , Nervio Coclear/fisiología , Vigilia/fisiología , Tecnología Inalámbrica/instrumentación , Vías Auditivas/fisiología , Audiometría de Respuesta Evocada/métodos , Modelos Animales , Percepción Auditiva/fisiología , Cóclea/fisiología , Percepción Visual , Factores de TiempoRESUMEN
The current study investigated the effect of lower frequency input on stream segregation acuity in older, normal hearing adults. Using event-related brain potentials (ERPs) and perceptual performance measures, we previously showed that stream segregation abilities were less proficient in older compared to younger adults. However, in that study we used frequency ranges greater than 1500 Hz. In the current study, we lowered the target frequency range below 1500 Hz and found similar stream segregation abilities in younger and older adults. These results indicate that the perception of complex auditory scenes is influenced by the spectral content of the auditory input and suggest that lower frequency ranges of input in older adults may facilitate listening ability in complex auditory environments. These results also have implications for the advancement of prosthetic devices.
Asunto(s)
Estimulación Acústica , Envejecimiento , Percepción Auditiva , Electroencefalografía , Potenciales Evocados Auditivos , Humanos , Anciano , Masculino , Femenino , Adulto , Adulto Joven , Envejecimiento/fisiología , Envejecimiento/psicología , Percepción Auditiva/fisiología , Factores de Edad , Persona de Mediana Edad , Umbral Auditivo , Vías Auditivas/fisiología , AudiciónRESUMEN
A major challenge in neuroscience is to understand how neural representations of sensory information are transformed by the network of ascending and descending connections in each sensory system. By recording from neurons at several levels of the auditory pathway, we show that much of the nonlinear encoding of complex sounds in auditory cortex can be explained by transformations in the midbrain and thalamus. Modeling cortical neurons in terms of their inputs across these subcortical populations enables their responses to be predicted with unprecedented accuracy. By contrast, subcortical responses cannot be predicted from descending cortical inputs, indicating that ascending transformations are irreversible, resulting in increasingly lossy, higher-order representations across the auditory pathway. Rather, auditory cortex selectively modulates the nonlinear aspects of thalamic auditory responses and the functional coupling between subcortical neurons without affecting the linear encoding of sound. These findings reveal the fundamental role of subcortical transformations in shaping cortical responses.
Asunto(s)
Corteza Auditiva , Tálamo , Corteza Auditiva/fisiología , Animales , Tálamo/fisiología , Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Sonido , Estimulación Acústica , Modelos Neurológicos , Mesencéfalo/fisiología , Neuronas/fisiologíaRESUMEN
OBJECTIVE: The acoustic change complex (ACC) is a cortical auditory evoked potential (CAEP) and can be elicited by a change in an otherwise continuous sound. The ACC has been highlighted as a promising tool in the assessment of sound and speech discrimination capacity, and particularly for difficult-to-test populations such as infants with hearing loss, due to the objective nature of ACC measurements. Indeed, there is a pressing need to develop further means to accurately and thoroughly establish the hearing status of children with hearing loss, to help guide hearing interventions in a timely manner. Despite the potential of the ACC method, ACC measurements remain relatively rare in a standard clinical settings. The objective of this study was to perform an up-to-date systematic review on ACC measurements in children, to provide greater clarity and consensus on the possible methodologies, applications, and performance of this technique, and to facilitate its uptake in relevant clinical settings. DESIGN: Original peer-reviewed articles conducting ACC measurements in children (< 18 years). Data were extracted and summarised for: (1) participant characteristics; (2) ACC methods and auditory stimuli; (3) information related to the performance of the ACC technique; (4) ACC measurement outcomes, advantages, and challenges. The systematic review was conducted using PRISMA guidelines for reporting and the methodological quality of included articles was assessed. RESULTS: A total of 28 studies were identified (9 infant studies). Review results show that ACC responses can be measured in infants (from < 3 months), and there is evidence of age-dependency, including increased robustness of the ACC response with increasing childhood age. Clinical applications include the measurement of the neural capacity for speech and non-speech sound discrimination in children with hearing loss, auditory neuropathy spectrum disorder (ANSD) and central auditory processing disorder (CAPD). Additionally, ACCs can be recorded in children with hearing aids, auditory brainstem implants, and cochlear implants, and ACC results may guide hearing intervention/rehabilitation strategies. The review identified that the time taken to perform ACC measurements was often lengthy; the development of more efficient ACC test procedures for children would be beneficial. Comparisons between objective ACC measurements and behavioural measures of sound discrimination showed significant correlations for some, but not all, included studies. CONCLUSIONS: ACC measurements of the neural capacity to discriminate between speech and non-speech sounds are feasible in infants and children, and a wide range of possible clinical applications exist, although more time-efficient procedures would be advantageous for clinical uptake. A consideration of age and maturational effects is recommended, and further research is required to investigate the relationship between objective ACC measures and behavioural measures of sound and speech perception for effective clinical implementation.
Asunto(s)
Estimulación Acústica , Percepción Auditiva , Potenciales Evocados Auditivos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Factores de Edad , Corteza Auditiva/fisiología , Corteza Auditiva/fisiopatología , Vías Auditivas/fisiopatología , Vías Auditivas/fisiología , Audición , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/rehabilitación , Personas con Deficiencia Auditiva/psicología , Personas con Deficiencia Auditiva/rehabilitación , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Pruebas de Discriminación del HablaRESUMEN
The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well-characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non-owl avian IC. Single-unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.
Asunto(s)
Estimulación Acústica , Pollos , Señales (Psicología) , Colículos Inferiores , Localización de Sonidos , Animales , Colículos Inferiores/fisiología , Pollos/fisiología , Localización de Sonidos/fisiología , Estimulación Acústica/métodos , Vías Auditivas/fisiología , Estrigiformes/fisiología , Neuronas/fisiologíaRESUMEN
Sound-source localization is based on spatial cues arising due to interactions of sound waves with the torso, head and ears. Here, we evaluated neural responses to free-field sound sources in the central nucleus of the inferior colliculus (CIC), the medial geniculate body (MGB) and the primary auditory cortex (A1) of Mongolian gerbils. Using silicon probes we recorded from anaesthetized gerbils positioned in the centre of a sound-attenuating, anechoic chamber. We measured rate-azimuth functions (RAFs) with broad-band noise of varying levels presented from loudspeakers spanning 210° in azimuth and characterized RAFs by calculating spatial centroids, Equivalent Rectangular Receptive Fields (ERRFs), steepest slope locations and spatial-separation thresholds. To compare neuronal responses with behavioural discrimination thresholds from the literature we performed a neurometric analysis based on signal-detection theory. All structures demonstrated heterogeneous spatial tuning with a clear dominance of contralateral tuning. However, the relative amount of contralateral tuning decreased from the CIC to A1. In all three structures spatial tuning broadened with increasing sound-level. This effect was strongest in CIC and weakest in A1. Neurometric spatial-separation thresholds compared well with behavioural discrimination thresholds for locations directly in front of the animal. Our findings contrast with those reported for another rodent, the rat, which exhibits homogenous and sharply delimited contralateral spatial tuning. Spatial tuning in gerbils resembles more closely the tuning reported in A1 of cats, ferrets and non-human primates. Interestingly, gerbils, in contrast to rats, share good low-frequency hearing with carnivores and non-human primates, which may account for the observed spatial tuning properties.
Asunto(s)
Vías Auditivas , Gerbillinae , Localización de Sonidos , Animales , Gerbillinae/fisiología , Localización de Sonidos/fisiología , Vías Auditivas/fisiología , Masculino , Corteza Auditiva/fisiología , Colículos Inferiores/fisiología , Cuerpos Geniculados/fisiología , Femenino , Estimulación Acústica/métodos , Neuronas/fisiologíaRESUMEN
This study investigated the morphology of the functional near-infrared spectroscopy (fNIRS) response to speech sounds measured from 16 sleeping infants and how it changes with repeated stimulus presentation. We observed a positive peak followed by a wide negative trough, with the latter being most evident in early epochs. We argue that the overall response morphology captures the effects of two simultaneous, but independent, response mechanisms that are both activated at the stimulus onset: one being the obligatory response to a sound stimulus by the auditory system, and the other being a neural suppression effect induced by the arousal system. Because the two effects behave differently with repeated epochs, it is possible to mathematically separate them and use fNIRS to study factors that affect the development and activation of the arousal system in infants. The results also imply that standard fNIRS analysis techniques need to be adjusted to take into account the possibilities of multiple simultaneous brain systems being activated and that the response to a stimulus is not necessarily stationary.
Asunto(s)
Estimulación Acústica , Nivel de Alerta , Sueño , Espectroscopía Infrarroja Corta , Humanos , Espectroscopía Infrarroja Corta/métodos , Estimulación Acústica/métodos , Lactante , Sueño/fisiología , Femenino , Masculino , Nivel de Alerta/fisiología , Percepción del Habla/fisiología , Corteza Auditiva/fisiología , Corteza Auditiva/diagnóstico por imagen , Vías Auditivas/fisiología , Mapeo Encefálico/métodos , Factores de Tiempo , Factores de Edad , Oxihemoglobinas/metabolismoRESUMEN
Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.
Asunto(s)
Estimulación Acústica , Vías Auditivas , Inhibición Prepulso , Reflejo de Sobresalto , Cuerpo Trapezoide , Animales , Inhibición Prepulso/fisiología , Masculino , Cuerpo Trapezoide/metabolismo , Cuerpo Trapezoide/fisiología , Vías Auditivas/fisiología , Vías Auditivas/metabolismo , Ratas Sprague-Dawley , Saporinas/metabolismo , Colina O-Acetiltransferasa/metabolismo , Neuronas Colinérgicas/metabolismo , Neuronas Colinérgicas/fisiología , Proteínas Inactivadoras de Ribosomas Tipo 1 , Potenciales Evocados Auditivos del Tronco Encefálico , Inmunotoxinas , Nervio Coclear/metabolismo , Nervio Coclear/fisiología , RatasRESUMEN
The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super-aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co-cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region-specific organoids and these organoids are assembled in the nanofiber-combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss.
Asunto(s)
Nanotubos de Carbono , Nanotubos de Carbono/química , Humanos , Animales , Ratones , Vías Auditivas/fisiología , Corteza Auditiva/fisiología , Neuronas/fisiología , Cóclea/fisiologíaRESUMEN
The encoding of acoustic stimuli requires precise neuron timing. Auditory neurons in the cochlear nucleus (CN) and brainstem are well suited for accurate analysis of fast acoustic signals, given their physiological specializations of fast membrane time constants, fast axonal conduction, and reliable synaptic transmission. The medial olivocochlear (MOC) neurons that provide efferent inhibition of the cochlea reside in the ventral brainstem and participate in these fast neural circuits. However, their modulation of cochlear function occurs over time scales of a slower nature. This suggests the presence of mechanisms that reduce MOC inhibition of cochlear function. To determine how monaural excitatory and inhibitory synaptic inputs integrate to affect the timing of MOC neuron activity, we developed a novel in vitro slice preparation ("wedge-slice"). The wedge-slice maintains the ascending auditory nerve root, the entire CN and projecting axons, while preserving the ability to perform visually guided patch-clamp electrophysiology recordings from genetically identified MOC neurons. The "in vivo-like" timing of the wedge-slice demonstrates that the inhibitory pathway accelerates relative to the excitatory pathway when the ascending circuit is intact, and the CN portion of the inhibitory circuit is precise enough to compensate for reduced precision in later synapses. When combined with machine learning PSC analysis and computational modeling, we demonstrate a larger suppression of MOC neuron activity when the inhibition occurs with in vivo-like timing. This delay of MOC activity may ensure that the MOC system is only engaged by sustained background sounds, preventing a maladaptive hypersuppression of cochlear activity.
Asunto(s)
Vías Auditivas , Núcleo Coclear , Inhibición Neural , Neuronas Eferentes , Animales , Ratones , Núcleo Coclear/fisiología , Núcleo Coclear/citología , Inhibición Neural/fisiología , Neuronas Eferentes/fisiología , Neuronas Eferentes/efectos de los fármacos , Vías Auditivas/fisiología , Femenino , Masculino , Nervio Coclear/fisiología , Técnicas de Placa-ClampRESUMEN
Many neurons in the central nucleus of the inferior colliculus (IC) show sensitivity to interaural time differences (ITDs), which is thought to be relayed from the brainstem. However, studies with interaural phase modulation of pure tones showed that IC neurons have a sensitivity to changes in ITD that is not present at the level of the brainstem. This sensitivity has been interpreted as a form of sensitivity to motion. A new type of stimulus is used here to study the sensitivity of IC neurons to dynamic changes in ITD, in which broad- or narrowband stimuli are swept through a range of ITDs with arbitrary start-ITD, end-ITD, speed, and direction. Extracellular recordings were obtained under barbiturate anesthesia in the cat. We applied the same analyses as previously introduced for the study of responses to tones. We find effects of motion which are similar to those described in response to interaural phase modulation of tones. The size of the effects strongly depended on the motion parameters but was overall smaller than reported for tones. We found that the effects of motion could largely be explained by the temporal response pattern of the neuron such as adaptation and build-up. Our data add to previous evidence questioning true coding of motion at the level of the IC.
Asunto(s)
Estimulación Acústica , Colículos Inferiores , Ruido , Animales , Gatos , Colículos Inferiores/fisiología , Neuronas/fisiología , Vías Auditivas/fisiología , Localización de Sonidos , Factores de Tiempo , Mesencéfalo/fisiología , Percepción de MovimientoRESUMEN
Linking sensory input and its consequences is a fundamental brain operation. During behavior, the neural activity of neocortical and limbic systems often reflects dynamic combinations of sensory and task-dependent variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur outside of the forebrain is less clear. Here, we conduct cellular-resolution two-photon Ca2+ imaging in the superficial "shell" layers of the inferior colliculus (IC), as head-fixed mice of either sex perform a reward-based psychometric auditory task. We find that the activity of individual shell IC neurons jointly reflects auditory cues, mice's actions, and behavioral trial outcomes, such that trajectories of neural population activity diverge depending on mice's behavioral choice. Consequently, simple classifier models trained on shell IC neuron activity can predict trial-by-trial outcomes, even when training data are restricted to neural activity occurring prior to mice's instrumental actions. Thus, in behaving mice, auditory midbrain neurons transmit a population code that reflects a joint representation of sound, actions, and task-dependent variables.
Asunto(s)
Percepción Auditiva , Colículos Inferiores , Animales , Ratones , Masculino , Colículos Inferiores/fisiología , Femenino , Percepción Auditiva/fisiología , Estimulación Acústica/métodos , Mesencéfalo/fisiología , Vías Auditivas/fisiología , Ratones Endogámicos C57BL , Neuronas/fisiología , RecompensaRESUMEN
The zebrafish, a widely used model in neurobiology, relies on hearing in aquatic environments. Unfortunately, its auditory pathways have mainly been studied in larvae. In this study, we examined the involvement of the anterior tuberal nucleus (AT) in auditory processing in adult zebrafish. Our tract-tracing experiments revealed that the dorsal subdivision of AT is strongly bidirectionally connected to the central nucleus of the torus semicircularis (TSc), a major auditory nucleus in fishes. Immunohistochemical visualization of the ribosomal protein S6 (pS6) phosphorylation to map neural activity in response to auditory stimulation substantiated this finding: the dorsal but not the ventral part of AT responded strongly to auditory stimulation. A similar response to auditory stimulation was present in the TSc but not in the nucleus isthmi, a visual region, which we used as a control for testing if the pS6 activation was specific to the auditory stimulation. We also measured the time course of pS6 phosphorylation, which was previously unreported in teleost fish. After auditory stimulation, we found that pS6 phosphorylation peaked between 100 and 130â min and returned to baseline levels after 190â min. This information will be valuable for the design of future pS6 experiments. Our results suggest an anatomical and functional subdivision of AT, where only the dorsal part connects to the auditory network and processes auditory information.