Auditory Neurophysiology publications

This study focused on mechanisms underlying azimuth selectivity in the primary auditory cortex (A1) of pallid bats. The pallid bat listens to prey-generated noise (5-35 kHz) to localize and hunt terrestrial prey. The region of A1 tuned between 5 and 35 kHz consists of two clusters of neurons distinguished by interaural intensity difference (IID) selectivity: binaurally inhibited (EI) and peaked. The first aim of this study was to use sequential dichotic/free-field stimulation to test the hypothesis that IID is the primary cue underlying azimuth selectivity in neurons tuned in the prey-generated noise frequency band. IID selectivity and ear directionality at the neuron's characteristic frequency (CF) were used to predict azimuth selectivity functions. The predicted azimuth selectivity was compared with the actual azimuth selectivity from the same neurons. Prediction accuracy was similarly high for EI neurons and peaked neurons with low CF, whereas predictions were increasingly inaccurate with increasing CF among the peaked neurons. The second aim of this study was to compare azimuth selectivity obtained with noise and CF tones to determine the extent to which stimulus bandwidth influences azimuth selectivity in neurons with different binaural properties. The azimuth selectivity functions were similar for the two stimuli in the majority of EI neurons. A greater percentage of peaked neurons showed differences in their azimuth selectivity for noise and tones. This included neurons with multiple peaks when tested with tones and a single peak when tested with noise. Taken together, data from the two aims suggest that azimuth tuning of EI neurons is primarily dictated by IID sensitivity at CF. Peaked neurons, particularly those with high CF, may integrate IID sensitivity across frequency to generate azimuth selectivity for broadband sound. The data are consistent with those found in cat and ferret A1 in that binaurally facilitated neurons depend to a greater extent (compared to EI neurons) on spectral integration of binaural properties to generate azimuth selectivity for broadband stimuli.

The acoustic rearing environment can alter central auditory coding properties, yet altered neural coding is seldom linked with specific deficits to adult perceptual skills. To test whether developmental hearing loss resulted in comparable changes to perception and sensory coding, we examined behavioral and neural detection thresholds for sinusoidally amplitude modulated (sAM) stimuli. Behavioral sAM detection thresholds for slow (5 Hz) modulations were significantly worse for animals reared with bilateral conductive hearing loss (CHL), as compared to controls. This difference could not be attributed to hearing thresholds, proficiency at the task, or proxies for attention. Detection thresholds across the groups did not differ for fast (100 Hz) modulations, a result paralleling that seen in humans. Neural responses to sAM stimuli were recorded in single auditory cortex neurons from separate groups of awake animals. Neurometric analyses indicated equivalent thresholds for the most sensitive neurons, but a significantly poorer detection threshold for slow modulations across the population of CHL neurons as compared to controls. The magnitude of the neural deficit matched that of the behavioral differences, suggesting that a reduction of sensory information can account for limitations to perceptual skills.

Brain damage resulting in loss of sensory stimulation can induce reorganization of sensory maps in cerebral cortex. Previous research on recovery from brain damage has focused primarily on adaptive plasticity within the affected modality. Less attention has been paid to maladaptive plasticity that may arise as a result of ectopic innervation from other modalities. Using ferrets in which neonatal midbrain damage results in diversion of retinal projections to the auditory thalamus, we investigated how auditory cortical function is impacted by the resulting ectopic visual activation. We found that, although auditory neurons in cross-modal auditory cortex (XMAC) retained sound frequency tuning, their thresholds were increased, their tuning was broader, and tonotopic order in their frequency maps was disturbed. Multisensory neurons in XMAC also exhibited frequency tuning, but they had longer latencies than normal auditory neurons, suggesting they arise from multisynaptic, non-geniculocortical sources. In a control group of animals with neonatal deafferentation of auditory thalamus but without redirection of retinal axons, tonotopic order and sharp tuning curves were seen, indicating that this aspect of auditory function had developed normally. This result shows that the compromised auditory function in XMAC results from invasion by ectopic visual inputs and not from deafferentation. These findings suggest that the cross-modal plasticity that commonly occurs after loss of sensory input can significantly interfere with recovery from brain damage and that mitigation of maladaptive effects is critical to maximizing the potential for recovery.

Suppression of ipsilateral distortion product otoacoustic emissions (DPOAEs) by contralateral noise is used in humans and animals to assay the strength of sound-evoked negative feedback from the medial olivocochlear (MOC) efferent pathway. However, depending on species and anesthesia, contributions of other feedback systems to the middle or inner ear can cloud the interpretation. Here, contributions of MOC and middle-ear muscle reflexes, as well as autonomic feedback, to contra-noise suppression in anesthetized mice are dissected by selectively eliminating each pathway by surgical transection, pharmacological blockade, or targeted gene deletion. When ipsilateral DPOAEs were evoked by low-level primaries, contra-noise suppression was typically ∼1 dB with contra-noise levels around 95 dB SPL, and it always disappeared upon contralateral cochlear destruction. Lack of middle-ear muscle contribution was suggested by persistence of contra-noise suppression after paralysis with curare, tensor tympani cauterization, or section of the facial nerve. Contribution of cochlear sympathetics was ruled out by studying mutant mice lacking adrenergic signaling (dopamine β-hydroxylase knockouts). Surprisingly, contra-noise effects on low-level DPOAEs were also not diminished by eliminating the MOC system pharmacologically (strychnine), surgically, or by deletion of relevant cholinergic receptors (α9/α10). In contrast, when ipsilateral DPOAEs were evoked by high-level primaries, the contra-noise suppression, although comparable in magnitude, was largely eliminated by MOC blockade or section. Possible alternate pathways are discussed for the source of contra-noise-evoked effects at low ipsilateral levels.

Stimulus-locked temporal codes are increasingly seen as relevant to perception. The timing of action potentials typically varies with stimulus intensity, and the invariance of temporal representations with intensity is therefore an issue. We examine the timing of action potentials in cat auditory nerve to broadband noise presented at different intensities, using an analysis inspired by coincidence detection and by the binaural "latency hypothesis." It is known that the two cues for azimuthal sound localization, interaural intensity or level differences and interaural time differences (ITDs), interact perceptually. According to the latency hypothesis, the increase in intensity for the ear nearest to a sound source off the midline causes a decrease in response latency in that ear relative to the other ear. We found that changes in intensity cause small but systematic shifts in the ongoing timing of responses in the auditory nerve, generally but not always resulting in shorter delays between stimulus onset and neural response for increasing intensity. The size of the temporal shifts depends on characteristic frequency with a pattern indicating a fine-structure and an envelope response regime. Overall, the results show that ongoing timing is remarkably stable with intensity at the most peripheral neural level. The results are not consistent in a simple way with the latency hypothesis, but because of the acute sensitivity to ITDs, the subtle effects of intensity on timing may nevertheless have perceptual consequences.

Topographically organized maps of the sensory receptor epithelia are regarded as cornerstones of cortical organization as well as valuable readouts of diverse biological processes ranging from evolution to neural plasticity. However, maps are most often derived from multiunit activity recorded in the thalamic input layers of anesthetized animals using near-threshold stimuli. Less distinct topography has been described by studies that deviated from the formula above, which brings into question the generality of the principle. Here, we explicitly compared the strength of tonotopic organization at various depths within core and belt regions of the auditory cortex using electrophysiological measurements ranging from single units to delta-band local field potentials (LFP) in the awake and anesthetized mouse. Unit recordings in the middle cortical layers revealed a precise tonotopic organization in core, but not belt, regions of auditory cortex that was similarly robust in awake and anesthetized conditions. In core fields, tonotopy was degraded outside the middle layers or when LFP signals were substituted for unit activity, due to an increasing proportion of recording sites with irregular tuning for pure tones. However, restricting our analysis to clearly defined receptive fields revealed an equivalent tonotopic organization in all layers of the cortical column and for LFP activity ranging from gamma to theta bands. Thus, core fields represent a transition between topographically organized simple receptive field arrangements that extend throughout all layers of the cortical column and the emergence of nontonotopic representations outside the input layers that are further elaborated in the belt fields.

Inhibitory interneurons regulate the responses of cortical circuits. In auditory cortical areas, inhibition from these neurons narrows spectral tuning and shapes response dynamics. Acute disruptions of inhibition expand spectral receptive fields. However, the effects of long-term perturbations of inhibitory circuitry on auditory cortical responses are unknown. We ablated ∼30% of dendrite-targeting cortical inhibitory interneurons after the critical period by studying mice with a conditional deletion of Dlx1 . Following the loss of interneurons, baseline firing rates rose and tone-evoked responses became less sparse in auditory cortex. However, contrary to acute blockades of inhibition, the sizes of spectral receptive fields were reduced, demonstrating both higher thresholds and narrower bandwidths. Furthermore, long-latency responses at the edge of the receptive field were absent. On the basis of changes in response dynamics, the mechanism for the reduction in receptive field size appears to be a compensatory loss of cortico-cortically (CC) driven responses. Our findings suggest chronic conditions that feature changes in inhibitory circuitry are not likely to be well modeled by acute network manipulations, and compensation may be a critical component of chronic neuronal conditions.

This report introduces a system for the objective physiological classification of single-unit activity in the anteroventral cochlear nucleus (AVCN) of anesthetized CBA/129 and CBA/CaJ mice. As in previous studies, the decision criteria are based on the temporal properties of responses to short tone bursts that are visualized in the form of peri-stimulus time histograms (PSTHs). Individual unit types are defined by the statistical distribution of quantifiable metrics that relate to the onset latency, regularity, and adaptation of sound-driven discharge rates. Variations of these properties reflect the unique synaptic organizations and intrinsic membrane properties that dictate the selective tuning of sound coding in the AVCN. When these metrics are applied to the mouse AVCN, responses to best frequency (BF) tones reproduce the major PSTH patterns that have been previously demonstrated in other mammalian species. The consistency of response types in two genetically diverse strains of laboratory mice suggests that the present classification system is appropriate for additional strains with normal peripheral function. The general agreement of present findings to established classifications validates laboratory mice as an adequate model for general principles of mammalian sound coding. Nevertheless, important differences are noted for the reliability of specialized endbulb transmission within the AVCN, suggesting less secure temporal coding in this high-frequency species.

Auditory brainstem responses (ABRs), and envelope and frequency following responses (EFRs and FFRs) are widely used to study aberrant auditory processing in conditions such as aging. We have previously reported age-related deficits in auditory processing for rapid amplitude modulation (AM) frequencies using EFRs recorded from a single channel. However, sensitive testing of EFRs along a wide range of modulation frequencies is required to gain a more complete understanding of the auditory processing deficits. In this study, ABRs and EFRs were recorded simultaneously from two electrode configurations in young and old Fischer-344 rats, a common auditory aging model. Analysis shows that the two channels respond most sensitively to complementary AM frequencies. Channel 1, recorded from Fz to mastoid, responds better to faster AM frequencies in the 100-700 Hz range of frequencies, while Channel 2, recorded from the inter-aural line to the mastoid, responds better to slower AM frequencies in the 16-100 Hz range. Simultaneous recording of Channels 1 and 2 using AM stimuli with varying sound levels and modulation depths show that age-related deficits in temporal processing are not present at slower AM frequencies but only at more rapid ones, which would not have been apparent recording from either channel alone. Comparison of EFRs between un-anesthetized and isoflurane-anesthetized recordings in young animals, as well as comparison with previously published ABR waveforms, suggests that the generators of Channel 1 may emphasize more caudal brainstem structures while those of Channel 2 may emphasize more rostral auditory nuclei including the inferior colliculus and the forebrain, with the boundary of separation potentially along the cochlear nucleus/superior olivary complex. Simultaneous two-channel recording of EFRs help to give a more complete understanding of the properties of auditory temporal processing over a wide range of modulation frequencies which is useful in understanding neural representations of sound stimuli in normal, developmental or pathological conditions.

Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

Sparse redundancy reducing codes have been proposed as efficient strategies for representing sensory stimuli. A prevailing hypothesis suggests that sensory representations shift from dense redundant codes in the periphery to selective sparse codes in cortex. We propose an alternative framework where sparseness and redundancy depend on sensory integration time scales and demonstrate that the central nucleus of the inferior colliculus (ICC) of cats encodes sound features by precise sparse spike trains. Direct comparisons with auditory cortical neurons demonstrate that ICC responses were sparse and uncorrelated as long as the spike train time scales were matched to the sensory integration time scales relevant to ICC neurons. Intriguingly, correlated spiking in the ICC was substantially lower than predicted by linear or nonlinear models and strictly observed for neurons with best frequencies within a "critical band," the hallmark of perceptual frequency resolution in mammals. This is consistent with a sparse asynchronous code throughout much of the ICC and a complementary correlation code within a critical band that may allow grouping of perceptually relevant cues.

Background In a natural environment, contextual noise frequently occurs with a signal sound for detection or discrimination in a temporal relation. However, the representation of sound frequency by auditory cortical neurons in a noisy environment is not fully understood. Therefore, the purpose of this study was to explore the impact of contextual noise on the cortical tuning to signal sound frequency in order to better understand the mechanism of cortical frequency coding in a complex acoustical environment. Results We compared the excitatory frequency-level receptive fields (FLRFs) of neurons in the rat primary auditory cortex determined under both quiet and preceding noise conditions. Based on the changes of minimum threshold and the extent of FLRF of auditory cortical neurons, we found that the FLRFs of a cortical neuron were modulated dynamically by a varying preceding noise. When the interstimulus interval between noise and the probe tone was constant, the modulation of the FLRF increased as the level of noise was increased. If the preceding noise level was constant, the modulation decreased when the interstimulus interval was increased. Preceding noise sharpened the bandwidth of the FLRFs of 47.6% tested neurons. Moreover, preceding noise shifted the CFs of 47.6% neurons by more than 0.25 octaves, while the CFs of the rest of the neurons remained relatively unchanged. Conclusions The results indicate that the cortical representation of sound frequency is dynamically modulated by contextual acoustical environment, and that there are cortical neurons whose characteristic frequencies were resistant to the interference of contextual noise.

The ferret ( Mustela putorius ) is a medium‐sized, carnivorous mammal with good low‐frequency hearing; it is relatively easy to train, and there is therefore a good body of behavioural data detailing its detection thresholds and localization abilities. However, despite extensive studies of the physiology of the central nervous system of the ferret, even extending to the prefrontal cortex, little is known of the functioning of the auditory periphery. Here, we provide an insight into this peripheral function by detailing responses of single auditory nerve fibres. Our expectation was that the ferret auditory nerve responsiveness would be similar that of its near relative, the cat. However, by comparing a range of variables (the frequency tuning, the variation of rate–level functions with spontaneous rate, and the high‐frequency cut‐off of phase locking) across several species, we show that the auditory nerve (and hence cochlea) in the ferret is more similar to that of the guinea‐pig and chinchilla than to that of the cat. Animal models of hearing are often chosen on the basis of the similarity of their audiogram to that of the human, particularly in the low‐frequency region. We show here that whereas the ferret hears well at low frequencies, this is likely to occur via fibres with higher characteristic frequencies. These qualitative differences in response characteristics in auditory nerve fibres are important in interpreting data across all of auditory science, as it has been argued recently that tuning in animals is broader than in humans.

Large conductance, voltage‐ and Ca 2+ ‐activated K + (BK) channels in inner hair cells (IHCs) of the cochlea are essential for hearing. However, germ‐line deletion of BKα, the pore‐forming subunit KCNMA1 of the BK channel, surprisingly did not affect hearing thresholds in the first postnatal weeks, even though altered IHC membrane time constants, decreased IHC receptor potential alternating current/direct current ratio, and impaired spike timing of auditory fibers were reported in these mice. To investigate the role of IHC BK channels for central auditory processing, we generated a conditional mouse model with hair cell‐specific deletion of BKα from postnatal day 10 onward. This had an unexpected effect on temporal coding in the central auditory system: neuronal single and multiunit responses in the inferior colliculus showed higher excitability and greater precision of temporal coding that may be linked to the improved discrimination of temporally modulated sounds observed in behavioral training. The higher precision of temporal coding, however, was restricted to slower modulations of sound and reduced stimulus‐driven activity. This suggests a diminished dynamic range of stimulus coding that is expected to impair signal detection in noise. Thus, BK channels in IHCs are crucial for central coding of the temporal fine structure of sound and for detection of signals in a noisy environment.—Kurt, S., Sausbier, M., Rüttiger, L., Brandt, N., Moeller, C. K., Kindler, J., Sausbier, U., Zimmermann, U., van Straaten, H., Neuhuber, W., Engel, J., Knipper, M., Ruth, P., Schulze, H. Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing. FASEB J. 26, 3834–3843 (2012). www.fasebj.org

Activation of nicotinic acetylcholine receptors (nAChRs) by systemic nicotine enhances sensory-cognitive function and sensory-evoked cortical responses. Although nAChRs mediate fast neurotransmission at many synapses in the nervous system, nicotinic regulation of cortical processing is neuromodulatory. To explore potential mechanisms of nicotinic neuromodulation, we examined whether intracellular signal transduction involving mitogen-activated protein kinase (MAPK) contributes to regulation of tone-evoked responses in primary auditory cortex (A1) in the mouse. Systemic nicotine enhanced characteristic frequency (CF) tone-evoked current-source density (CSD) profiles in A1, including the shortest-latency (presumed thalamocortical) current sink in layer 4 and longer-latency (presumed intracortical) sinks in layers 2–4, by increasing response amplitudes and decreasing response latencies. Microinjection of the MAPK kinase (MEK) inhibitor U0126 into the thalamus, targeting the auditory thalamocortical pathway, blocked the effect of nicotine on the initial (thalamocortical) CSD component but did not block enhancement of longer-latency (intracortical) responses. Conversely, microinjection of U0126 into supragranular layers of A1 blocked nicotine's effect on intracortical, but not thalamocortical, CSD components. Simultaneously with enhancement of CF-evoked responses, responses to spectrally distant (nonCF) stimuli were reduced, implying nicotinic “sharpening” of frequency receptive fields, an effect also blocked by MEK inhibition. Consistent with these physiological results, acoustic stimulation with nicotine produced immunolabel for activated MAPK in A1, primarily in layer 2/3 cell bodies. Immunolabel was blocked by intracortical microinjection of the nAChR antagonist dihydro-β-erythroidine, but not methyllycaconitine, implicating α4β2*, but not α7, nAChRs. Thus activation of MAPK in functionally distinct forebrain circuits—thalamocortical, local intracortical, and long-range intracortical—underlies nicotinic neuromodulation of A1.

To date, the functional and physiological impact on the mature brain of moderate-level environmental noises that do not cause noticeable peripheral deficits remains largely unstudied. Here we show that exposing adult rats to structured noise at a sound pressure level of 65 dB, which is markedly below the broadly accepted safety level standard, results in behavioural impairments and substantially impairs the function of the auditory cortex. The strong deterioration in cortical processing of acoustic inputs is independent of the modulation rates of structured noises. Almost equally strong effects result from 10-h daily versus 24-h daily exposure regimens. These results indicate that there can be substantial negative consequences for the auditory system documented at the cortical level, attributable to environmental exposure to structured noises delivered under conditions that do not directly impact hearing sensitivity. These noises are deemed to be 'safe' and are often present in modern human environments.

The dorsal cochlear nucleus (DCN) is a first relay of the central auditory system as well as a site for integration of multimodal information. Vesicular glutamate transporters VGLUT-1 and VGLUT-2 selectively package glutamate into synaptic vesicles and are found to have different patterns of organization in the DCN. Whereas auditory nerve fibers predominantly co-label with VGLUT-1, somatosensory inputs predominantly co-label with VGLUT-2. Here, we used retrograde and anterograde transport of fluorescent conjugated dextran amine (DA) to demonstrate that the lateral vestibular nucleus (LVN) exhibits ipsilateral projections to both fusiform and deep layers of the rat DCN. Stimulating the LVN induced glutamatergic synaptic currents in fusiform cells and granule cell interneurones. We combined the dextran amine neuronal tracing method with immunohistochemistry and showed that labeled projections from the LVN are co-labeled with VGLUT-2 by contrast to VGLUT-1. Wistar rats were exposed to a loud single tone (15 kHz, 110 dB SPL) for 6 hours. Five days after acoustic overexposure, the level of expression of VGLUT-1 in the DCN was decreased whereas the level of expression of VGLUT-2 in the DCN was increased including terminals originating from the LVN. VGLUT-2 mediated projections from the LVN to the DCN are likely to play a role in the head position in response to sound. Amplification of VGLUT-2 expression after acoustic overexposure could be a compensatory mechanism from vestibular inputs in response to hearing loss and to a decrease of VGLUT-1 expression from auditory nerve fibers.

Signal duration is important for identifying sound sources and determining signal meaning. Duration-tuned neurons (DTNs) respond preferentially to a range of stimulus durations and maximally to a best duration (BD). Duration-tuned neurons are found in the auditory midbrain of many vertebrates, although studied most extensively in bats. Studies of DTNs across vertebrates have identified cells with BDs and temporal response bandwidths that mirror the range of species-specific vocalizations. Neural tuning to stimulus duration appears to be universal among hearing vertebrates. Herein, we test the hypothesis that neural mechanisms underlying duration selectivity may be similar across vertebrates. We instantiated theoretical mechanisms of duration tuning in computational models to systematically explore the roles of excitatory and inhibitory receptor strengths, input latencies, and membrane time constant on duration tuning response profiles. We demonstrate that models of duration tuning with similar neural circuitry can be tuned with species-specific parameters to reproduce the responses of in vivo DTNs from the auditory midbrain. To relate and validate model output to in vivo responses, we collected electrophysiological data from the inferior colliculus of the awake big brown bat, Eptesicus fuscus , and present similar in vivo data from the published literature on DTNs in rats, mice, and frogs. Our results support the hypothesis that neural mechanisms of duration tuning may be shared across vertebrates despite species-specific differences in duration selectivity. Finally, we discuss how the underlying mechanisms of duration selectivity relate to other auditory feature detectors arising from the interaction of neural excitation and inhibition.

Objective: Sensorineural hearing loss leads to the progressive degeneration of spiral ganglion cells (SGC). Next to postoperative fibrous tissue growth, which should be suppressed to assure a close nerve-electrode interaction, the density of healthy SGC is one factor that influences the efficiency of cochlear implants (CI), the choice of treatment for affected patients. Rolipram, a phosphodiesterase-4 inhibitor, has proven neuroprotective and anti-inflammatory effects and might also reduce SGC degeneration and fibrosis, but it has to pass the cellular membrane to be biologically active. Methods: Lipidic nanocapsules (LNC) can be used as biodegradable drug carriers to increase the efficacy of conventional application methods. We examined the biological effects of rolipram and LNC's core encapsulated rolipram on SGC and dendritic cell (DC) tumor necrosis factor-α (TNF-α) production in vitro and on SGC survival in systemically-deafened guinea pigs in vivo. Results: Our results prove that rolipram does not have a beneficial effect on cultured SGC. Incorporation of rolipram in LNC increased the survival of SGC significantly. In the DC study, rolipram significantly inhibited TNF-α in a dose-dependent manner. The rolipram-loaded LNC provided a significant cytokine inhibition as well. In vivo data do not confirm the in vitro results. Conclusion: By transporting rolipram into the SGC cytoplasm, LNC enabled the neuroprotective effect of rolipram in vitro, but not in vivo. This might be due to dilution of test substances by perilymph or an inadequate release of rolipram based on differing in vivo and in vitro conditions. Nevertheless, based on in vitro results, proving a significantly increased neuronal survival when using LNC-rolipram compared to pure rolipram and pure LNC application, we believe that the combination of rolipram and LNC can potentially reduce neuronal degeneration and fibrosis after CI implantation. We conclude that rolipram is a promising drug that can be used in inner ear therapy and that LNC have potential as an inner ear drug-delivery system. Further experiments with modified conditions might reveal in vivo biological effects.

The ability to detect and track relevant acoustic signals embedded in a background of other sounds is crucial for hearing in complex acoustic environments. This ability is exemplified by a perceptual phenomenon known as “rhythmic masking release” (RMR). To demonstrate RMR, a sequence of tones forming a target rhythm is intermingled with physically identical “Distracter” sounds that perceptually mask the rhythm. The rhythm can be “released from masking” by adding “Flanker” tones in adjacent frequency channels that are synchronous with the Distracters. RMR represents a special case of auditory stream segregation, whereby the target rhythm is perceptually segregated from the background of Distracters when they are accompanied by the synchronous Flankers. The neural basis of RMR is unknown. Previous studies suggest the involvement of primary auditory cortex (A1) in the perceptual organization of sound patterns. Here, we recorded neural responses to RMR sequences in A1 of awake monkeys in order to identify neural correlates and potential mechanisms of RMR. We also tested whether two current models of stream segregation, when applied to these responses, could account for the perceptual organization of RMR sequences. Results suggest a key role for suppression of Distracter-evoked responses by the simultaneous Flankers in the perceptual restoration of the target rhythm in RMR. Furthermore, predictions of stream segregation models paralleled the psychoacoustics of RMR in humans. These findings reinforce the view that preattentive or “primitive” aspects of auditory scene analysis may be explained by relatively basic neural mechanisms at the cortical level.