Auditory Research publications

The intermediate nucleus of the lateral lemniscus (INLL) is a major input to the inferior colliculus (IC), the auditory midbrain center where multiple pathways converge to create neurons selective for specific temporal features of sound. However, little is known about how INLL processes auditory information or how it contributes to integrative processes at the IC. INLL receives excitatory projections from the cochlear nucleus and inhibitory projections from the medial nucleus of the trapezoid body (MNTB), so it must perform some form of integration. To address the question of what role inhibitory synaptic inputs play in the INLL of the big brown bat ( Eptesicus fuscus), we recorded sound-evoked responses of single neurons and iontophoretically applied bicuculline to block GABA A receptors or strychnine to block glycine receptors. Neither bicuculline nor strychnine had a consistent effect on response latency or frequency response areas. Bicuculline increased spike counts and response durations in most units, suggesting that GABAergic input suppressed the late part of the response and provided some gain control. Strychnine reduced the responses of some units with sustained discharge patterns to one or a few spikes at stimulus onset, but increased others. INLL is the only part of the auditory system where reduced responsiveness has been seen in vivo while blocking glycine. However, in vitro studies in the MNTB suggest that glycine can be facilitatory, possibly through presynaptic action. These results show that GABA consistently reduces spike counts and response durations, whereas glycine is suppressive in some INLL neurons but facilitatory in others.

An extension of the Wiener-Volterra theory to a Poisson-distributed impulse train input was used to characterize the temporal response properties of neurons in primary auditory cortex (AI) of the ketamine-anesthetized cat. Both first- and second-order “Poisson-Wiener” (PW) models were tested on their predictions of temporal modulation transfer functions (tMTFs), which were derived from extracellular spike responses to periodic click trains with click repetition rates of 2–64 Hz. Second-order (i.e., nonlinear) PW fits to the measured tMTFs could be described as very good in a majority of cases (e.g., predictability ≥80%) and were almost always superior to first-order (i.e., linear) fits. In all sampled neurons, second-order PW kernels showed strong compressive nonlinearities (i.e., a depression of the impulse response) but never expansive nonlinearities (i.e., a facilitation of the impulse response). In neurons with low-pass tMTFs, the depression decayed exponentially with the interstimulus lag, whereas in neurons with band-pass tMTFs, the depression was typically double-peaked, and the second peak occurred at a lag that correlated with the neuron's best modulation frequency. It appears that modulation-tuning in AI arises in part from an interplay of two nonlinear processes with distinct time courses.

The perception of two simultaneous tones was investigated in goldfish using classical respiratory conditioning and a stimulus generalization paradigm. Pairs of tones were used to make up a mixture of 150 Hz and a higher harmonic or a mistuned harmonic. Fish were conditioned to the two-tone mixture and then tested for generalization to several pure tones. The simultaneous tones tended to be segregated in perception, with the generalization gradient for single tones having two peaks corresponding to the frequencies of the tone pairs. There were no consistent differences in the generalization gradients following conditioning to harmonic or inharmonic tone pairs. In addition, experiments were carried out in which the two tones of the pair were heard on alternate trials, always as single tones, followed by generalization tests to single tones. There was more generalization in this experiment, reflecting the fact that conditioning and generalization test stimuli were both single tones. However, the shapes of the generalization gradients were similar to those in which fish were conditioned to two simultaneous tones, indicating that the simultaneity of the tones did not make them harder to segregate. As the frequency separation between the two components narrowed, segregation tended to fail.

Neural representation of pitch is influenced by lifelong experiences with music and language at both cortical and subcortical levels of processing. The aim of this article is to determine whether neural plasticity for pitch representation at the level of the brainstem is dependent upon specific dimensions of pitch contours that commonly occur as part of a native listener's language experience. Brainstem frequency following responses (FFRs) were recorded from Chinese and English participants in response to four Mandarin tonal contours presented in a nonspeech context in the form of iterated rippled noise. Pitch strength (whole contour, 250 msec; 40-msec segments) and pitch-tracking accuracy (whole contour) were extracted from the FFRs using autocorrelation algorithms. Narrow band spectrograms were used to extract spectral information. Results showed that the Chinese group exhibits smoother pitch tracking than the English group in three out of the four tones. Moreover, cross-language comparisons of pitch strength of 40-msec segments revealed that the Chinese group exhibits more robust pitch representation of those segments containing rapidly changing pitch movements across all four tones. FFR spectral data were complementary showing that the Chinese group exhibits stronger representation of multiple pitch-relevant harmonics relative to the English group across all four tones. These findings support the view that at early preattentive stages of subcortical processing, neural mechanisms underlying pitch representation are shaped by particular dimensions of the auditory stream rather than speech per se. Adopting a temporal correlation analysis scheme for pitch encoding, we propose that long-term experience sharpens the tuning characteristics of neurons along the pitch axis with enhanced sensitivity to linguistically relevant variations in pitch.

Background: The use of bilateral amplification is now common clinical practice for hearing aid users but not for cochlear implant recipients. In the past, most cochlear implant recipients were implanted in one ear and wore only a monaural cochlear implant processor. There has been recent interest in benefits arising from bilateral stimulation that may be present for cochlear implant recipients. One option for bilateral stimulation is the use of a cochlear implant in one ear and a hearing aid in the opposite nonimplanted ear (bimodal hearing). Purpose: This study evaluated the effect of wearing a cochlear implant in one ear and a digital hearing aid in the opposite ear on speech recognition and localization. Research Design: A repeated-measures correlational study was completed. Study Sample: Nineteen adult Cochlear Nucleus 24 implant recipients participated in the study. Intervention: The participants were fit with a Widex Senso Vita 38 hearing aid to achieve maximum audibility and comfort within their dynamic range. Data Collection and Analysis: Soundfield thresholds, loudness growth, speech recognition, localization, and subjective questionnaires were obtained six‐eight weeks after the hearing aid fitting. Testing was completed in three conditions: hearing aid only, cochlear implant only, and cochlear implant and hearing aid (bimodal). All tests were repeated four weeks after the first test session. Repeated-measures analysis of variance was used to analyze the data. Significant effects were further examined using pairwise comparison of means or in the case of continuous moderators, regression analyses. The speech-recognition and localization tasks were unique, in that a speech stimulus presented from a variety of roaming azimuths (140 degree loudspeaker array) was used. Results: Performance in the bimodal condition was significantly better for speech recognition and localization compared to the cochlear implant‐only and hearing aid‐only conditions. Performance was also different between these conditions when the location (i.e., side of the loudspeaker array that presented the word) was analyzed. In the bimodal condition, the speech-recognition and localization tasks were equal regardless of which side of the loudspeaker array presented the word, while performance was significantly poorer for the monaural conditions (hearing aid only and cochlear implant only) when the words were presented on the side with no stimulation. Binaural loudness summation of 1‐3 dB was seen in soundfield thresholds and loudness growth in the bimodal condition. Measures of the audibility of sound with the hearing aid, including unaided thresholds, soundfield thresholds, and the Speech Intelligibility Index, were significant moderators of speech recognition and localization. Based on the questionnaire responses, participants showed a strong preference for bimodal stimulation. Conclusions: These findings suggest that a well-fit digital hearing aid worn in conjunction with a cochlear implant is beneficial to speech recognition and localization. The dynamic test procedures used in this study illustrate the importance of bilateral hearing for locating, identifying, and switching attention between multiple speakers. It is recommended that unilateral cochlear implant recipients, with measurable unaided hearing thresholds, be fit with a hearing aid.

The interplay between excitation and inhibition in the auditory cortex is crucial for the processing of acoustic stimuli. However, the precise role that inhibition plays in the distributed cortical encoding of natural vocalizations has not been well studied. We recorded single units (SUs) and local field potentials (LFPs) in the awake mouse auditory cortex while presenting pup isolation calls to animals that either do (mothers) or do not (virgins) recognize the sounds as behaviorally relevant. In both groups, we observed substantial call-evoked inhibition. However, in mothers this was earlier, longer, stronger, and more stereotyped compared to virgins. This difference was most apparent for recording sites tuned to tone frequencies lower than the pup calls' high-ultrasonic frequency range. We hypothesize that this auditory cortical inhibitory plasticity improves pup call detection in a relatively specific manner by increasing the contrast between call-evoked responses arising from high-ultrasonic and lateral frequency neural populations.

Comparisons of left and right auditory input are required for sound source localization in most terrestrial vertebrates. Previous physiological and neuroanatomical studies have indicated that binaural convergence is present in the ascending auditory system of the toadfish. In this study, we introduce a new technique, otolith tipping, to reversibly alter directional auditory input to the central nervous system of a fish. The normal directional response pattern (DRP) was recorded extracellularly for auditory cells in the first-order descending octaval nucleus (DON) or the midbrain torus semicircularis (TS) using particle motion stimuli in the horizontal and mid-sagittal planes. The same stimuli were used during tipping of the saccular otolith to evaluate changes in the DRPs. Post-tipping DRPs were generated and compared with the pre-tipping DRPs to ensure that the data had been collected consistently from the same unit. In the DON, ipsilateral or contralateral tipping most often eliminated spike activity, but changes in spike rate(±) and DRP shape were also documented. In the TS, tipping most often caused a change in spike rate (±) and altered the shape or best axis of the DRP. The data indicate that there are complex interactions of excitatory and inhibitory inputs in the DON and TS resulting from the convergence of binaural inputs. As in anurans, but unlike other terrestrial vertebrates,binaural processing associated with encoding the direction of a sound source begins in the first-order auditory nucleus of this teleost.

Auditory thalamocortical connections are organized as parallel pathways originating in various nuclei of the medial geniculate body (MGB). The development of these pathways has not been studied. Therefore it remains unclear whether thalamocortical connections segregate before the onset of hearing or whether refinement of exuberant thalamocortical connections occurs following hearing onset. We studied this issue in the pallid bat. In adult pallid bats, parallel thalamocortical pathways represent two different sounds used in two different behaviors. The suprageniculate (SG) nucleus of the dorsal division of the MGB (MGBd) projects to a high‐frequency cortical region selective for the echolocation calls, but not to a low‐frequency cortical region sensitive to noise transients used in the localization of prey. Conversely, the ventral division (MGBv) projects to the low‐frequency, but not the high‐frequency, cortical region. Here we studied the development of these parallel pathways. Based on retrograde tracer injections in electrophysiologically characterized cortical loci, we show that there is an asymmetrical overlap in projection patterns from postnatal (P) day 15–60. The low‐frequency region receives extensive input from both the SG and the MGBv. In contrast, the high‐frequency region receives the great majority of its input from the SG, as in adults, whereas projections from the MGBv appear to make only a minor contribution, if any. By P150, these pathways are segregated and adult‐like. These data suggest that these anatomically segregated pathways arise through postnatal refinement of initially overlapping connections. J. Comp. Neurol. 515:231–242, 2009. © 2009 Wiley‐Liss, Inc.

Slow oscillations at frequencies <1 Hz manifest in many brain regions as discrete transitions between a depolarized up state and a hyperpolarized down state of the neuronal membrane potential. Although up and down states are known to differentially affect sensory-evoked responses, whether and how they are modulated by sensory stimuli are not well understood. In the present study, intracellular recording in anesthetized guinea pigs showed that membrane potentials of nonlemniscal auditory thalamic neurons exhibited spontaneous up/down transitions at random intervals in the range of 2–30 s, which could be entrained to a regular interval by repetitive sound stimuli. After termination of the entraining stimulation (ES), regular up/down transitions persisted for several cycles at the ES interval. Furthermore, the efficacy of weak sound stimuli in triggering the up-to-down transition was potentiated specifically at the ES interval for at least 10 min. Extracellular recordings in the auditory thalamus of unanesthetized guinea pigs also showed entrainment of slow oscillations by rhythmic sound stimuli during slow wave sleep. These results demonstrate a novel form of network plasticity, which could help to retain the information of stimulus interval on the order of seconds.

Usher syndrome 3A (USH3A) is an autosomal recessive disorder characterized by progressive loss of hearing and vision due to mutation in the clarin-1 (CLRN1) gene. Lack of an animal model has hindered our ability to understand the function of CLRN1 and the pathophysiology associated with USH3A. Here we report for the first time a mouse model for ear disease in USH3A. Detailed evaluation of inner ear phenotype in the Clrn1 knockout mouse (Clrn1(-/-)) coupled with expression pattern of Clrn1 in the inner ear are presented here. Clrn1 was expressed as early as embryonic day 16.5 in the auditory and vestibular hair cells and associated ganglionic neurons, with its expression being higher in outer hair cells (OHCs) than inner hair cells. Clrn1(-/-) mice showed early onset hearing loss that rapidly progressed to severe levels. Two to three weeks after birth (P14-P21), Clrn1(-/-) mice showed elevated auditory-evoked brainstem response (ABR) thresholds and prolonged peak and interpeak latencies. By P21, approximately 70% of Clrn1(-/-) mice had no detectable ABR and by P30 these mice were deaf. Distortion product otoacoustic emissions were not recordable from Clrn1(-/-) mice. Vestibular function in Clrn1(-/-) mice mirrored the cochlear phenotype, although it deteriorated more gradually than cochlear function. Disorganization of OHC stereocilia was seen as early as P2 and by P21 OHC loss was observed. In sum, hair cell dysfunction and prolonged peak latencies in vestibular and cochlear evoked potentials in Clrn1(-/-) mice strongly indicate that Clrn1 is necessary for hair cell function and associated neural activation.

Noise in animal housing facilities is an environmental variable that can affect hearing, behavior and physiology in mice. The authors measured sound levels in two rodent housing rooms (room 1 and room 2) during several 24-h periods. Room 1, which was subject to heavy personnel traffic, contained ventilated racks and static cages that housed large numbers of mice. Room 2 was accessed by only a few staff members, contained static cages only and housed fewer mice. In both rooms, background sound levels were usually about 80 dB, and transient noises caused sound levels to temporarily rise 30-40 dB above the baseline level; such peaks occurred frequently during work hours (8:30 AM to 4:30 PM) and infrequently during non-work hours. Noise peaks during work hours in room 1 occurred about two times as often as in room 2 (P = 0.01). Use of changing stations located in the rooms caused background noise to increase by about 10 dB. Loud noise and noise variability were attributed mainly to personnel activity. Attempts to reduce noise should concentrate on controlling sounds produced by in-room activities and experimenter traffic; this may reduce the variability of research outcomes and improve animal welfare.

In hair cells, mechanotransduction channels are gated by tip links, the extracellular filaments that consist of cadherin 23 (CDH23) and protocadherin 15 (PCDH15) and connect the stereocilia of each hair cell. However, which molecules mediate cadherin function at tip links is not known. Here we show that the PDZ-domain protein harmonin is a component of the upper tip-link density (UTLD), where CDH23 inserts into the stereociliary membrane. Harmonin domains that mediate interactions with CDH23 and F-actin control harmonin localization in stereocilia and are necessary for normal hearing. In mice expressing a mutant harmonin protein that prevents UTLD formation, the sensitivity of hair bundles to mechanical stimulation is reduced. We conclude that harmonin is a UTLD component and contributes to establishing the sensitivity of mechanotransduction channels to displacement.

Differences in sensory function between young (n = 42, 18-31 years old) and older (n = 137, 60-88 years old) adults were examined for auditory, visual, and tactile measures of threshold sensitivity and temporal acuity (gap-detection threshold). For all but one of the psychophysical measures (visual gap detection), multiple measures were obtained at different stimulus frequencies for each modality and task. This resulted in a total of 14 dependent measures, each based on four to six adaptive psychophysical estimates of 75% correct performance. In addition, all participants completed the Wechsler Adult Intelligence Scale (Wechsler, 1997). Mean data confirmed previously observed differences in performance between young and older adults for 13 of the 14 dependent measures (all but visual threshold at a flicker frequency of 4 Hz). Correlational and principal-components factor analyses performed on the data from the 137 older adults were generally consistent with task and modality independence of the psychophysical measures.

Two modified go/no-go tasks are compared for the measurement of frequency discrimination in albino rats. The first task required detection of an instantaneous, phase-matched frequency change, called a "tone-step," within a continuous reference tone. The more traditional second task required detection of a frequency change between repetitions of a reference sequence of repeating discrete tones. For each task frequency difference limens were measured over a range of reference frequencies from 2.31 to 27.7 kHz at 60 dB sound pressure level, with both upward and downward frequency shifts. All 24 subjects quickly learned the "tone-step" task to criterion, but only 13 could also learn the discrete tone task. Subjects' performance at either task generally improved with increasing reference frequency, and in both tasks upward frequency change thresholds were significantly higher than thresholds for downward changes. Overall mean Weber ratios were 1.73+/-0.27% for the "tone-step" task and 2.76+/-0.29% for the discrete tone task. However, subjects' performance on the "tone-step" task was not correlated with subsequent performance on the discrete tone task. We suggest that the lack of correspondence between tasks might be due to frequency discrimination processes interacting with short-term memory traces during inter-tone intervals in the discrete tone task.

Stress hormones released by an experience can modulate memory strength via the basolateral amygdala, which in turn acts on sites of memory storage such as the cerebral cortex [McGaugh, J. L. (2004). The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience, 27, 1-28]. Stimuli that acquire behavioral importance gain increased representation in the cortex. For example, learning shifts the tuning of neurons in the primary auditory cortex (A1) to the frequency of a conditioned stimulus (CS), and the greater the level of CS importance, the larger the area of representational gain [Weinberger, N. M. (2007). Associative representational plasticity in the auditory cortex: A synthesis of two disciplines. Learning & Memory, 14(1-2), 1-16]. The two lines of research suggest that BLA strengthening of memory might be accomplished in part by increasing the representation of an environmental stimulus. The present study investigated whether stimulation of the BLA can affect cortical memory representations. In male Sprague-Dawley rats studied under urethane general anesthesia, frequency receptive fields were obtained from A1 before and up to 75min after the pairing of a tone with BLA stimulation (BLAstm: 100 trials, 400ms, 100Hz, 400microA [+/-16.54]). Tone started before and continued after BLAstm. Group BLA/1.0 (n=16) had a 1s CS-BLAstm interval while Group BLA/1.6 (n=5) has a 1.6s interval. The BLA/1.0 group did develop specific tuning shifts toward and to the CS, which could change frequency tuning by as much as two octaves. Moreover, its shifts increased over time and were enduring, lasting 75min. However, group BLA/1.6 did not develop tuning shifts, indicating that precise CS-BLAstm timing is important in the anesthetized animal. Further, training in the BLA/1.0 paradigm but stimulating outside of the BLA did not produce tuning shifts. These findings demonstrate that the BLA is capable of exerting highly specific, enduring, learning-related modifications of stimulus representation in the cerebral cortex. These findings suggest that the ability of the BLA to alter specific cortical representations may underlie, at least in part, the modulatory influence of BLA activity on strengthening long-term memory.

Sound stimulates the tympanic membrane (TM) of anuran amphibians through multiple, poorly understood pathways. It is conceivable that interactions between the internal and external inputs to the TM contribute to the nonlinear effects that noise is known to produce at higher levels of the auditory pathway. To explore this issue, we conducted measurements of TM vibration in response to tones in the presence of noise in the frog Eupsophus calcaratus. Laser vibrometry revealed that the power spectra (n = 16) of the TM velocity in response to pure tones at a constant level of 80 dB sound-pressure level (SPL) had a maximum centered at an average frequency of 2,344 Hz (range 1,700-2,990 Hz) and a maximum velocity of 61.1 dB re 1 microm/s (range 42.9-66.6 dB re 1 microm/s). These TM-vibration velocity response profiles in the presence of increasing levels of 4-kHz band-pass noise were unaltered up to noise levels of 90 dB SPL. For the relatively low spectral densities of the noise used, the TM remains in its linear range. Such vibration patterns facilitate the detection of tonal signals in noise at the tympanic membrane and may underlie the remarkable vocal responsiveness maintained by males of E. calcaratus under noise interference.

Huia cavitympanum, an endemic Bornean frog, is the first amphibian species known to emit exclusively ultrasonic (i.e., >20 kHz) vocal signals. To test the hypothesis that these frogs use purely ultrasonic vocalizations for intraspecific communication, we performed playback experiments with male frogs in their natural calling sites. We found that the frogs respond with increased calling to broadcasts of conspecific calls containing only ultrasound. The field study was complemented by electrophysiological recordings from the auditory midbrain and by laser Doppler vibrometer measurements of the tympanic membrane's response to acoustic stimulation. These measurements revealed that the frog's auditory system is broadly tuned over high frequencies, with peak sensitivity occurring within the ultrasonic frequency range. Our results demonstrate that H. cavitympanum is the first non-mammalian vertebrate described to communicate with purely ultrasonic acoustic signals. These data suggest that further examination of the similarities and differences in the high-frequency/ultrasonic communication systems of H. cavitympanum and Odorrana tormota, an unrelated frog species that produces and detects ultrasound but does not emit exclusively ultrasonic calls, will afford new insights into the mechanisms underlying vertebrate high-frequency communication.

To identify sounds as novel, there must be some neural representation of commonly occurring sounds. Stimulus-specific adaptation (SSA) is a reduction in neural response to a repeated sound. Previous studies using an oddball stimulus paradigm have shown that SSA occurs at the cortex, but this study demonstrates that neurons in the inferior colliculus (IC) also show strong SSA using this paradigm. The majority (66%) of IC neurons showed some degree of SSA. Approximately 18% of neurons showed near-complete SSA. Neurons with SSA were found throughout the IC. Responses of IC neurons were reduced mainly during the onset component of the response, and latency was shorter in response to the oddball stimulus than to the standard. Neurons with near-complete SSA were broadly tuned to frequency, suggesting a high degree of convergence. Thus, some of the mechanisms that may underlie novelty detection and behavioral habituation to common sounds are already well developed at the midbrain.

The ventral and medial divisions of the medial geniculate body (MGBv and MGBm) respectively are the lemniscal and nonlemniscal thalamic auditory nuclei. Lemniscal neurons are narrowly frequency tuned and provide highly specific frequency information to the primary auditory cortex (AI), whereas nonlemniscal neurons are broadly frequency tuned and project widely to auditory cortical areas including AI. The MGBv and MGBm are presumably different not only in auditory signal processing, but also in eliciting cortical plastic changes. We electrically stimulated MGBv or MGBm neurons and found the following: (1) electric stimulation of narrowly frequency-tuned MGBv neurons evoked the shift of the frequency-tuning curves of AI neurons toward the tuning curves of the stimulated MGBv neurons. This shift was the same as that in the central nucleus of the inferior colliculus and AI elicited by focal electric stimulation of AI or auditory fear conditioning. The widths of the tuning curves of the AI neurons stayed the same or slightly increased. (2) Electric stimulation of broad frequency-tuned MGBm neurons augmented the auditory responses of AI neurons and broadened their frequency-tuning curves which did not shift. These cortical changes evoked by MGBv or MGBm neurons slowly disappeared over 45–60 min after the onset of the electric stimulation. Our findings indicate that lemniscal and nonlemniscal nuclei are indeed different in eliciting cortical plastic changes: the MGBv evokes tone-specific plasticity in AI for adjusting auditory signal processing in the frequency domain, whereas the MGBm evokes nonspecific plasticity in AI for increasing the sensitivity of cortical neurons.

Exogenous delivery of neurotrophic factors into the cochlea of deafened animals rescues spiral ganglion cells (SGCs) from degeneration. To be clinically relevant for human cochlear implant candidates, the protective effect of neurotrophins should persist after cessation of treatment and the treated SGCs should remain functional. In this study, the survival and functionality of SGCs were investigated after temporary treatment with brain-derived neurotrophic factor (BDNF). Guinea pigs in the experimental group were deafened, and 2 weeks later, the right cochleae were implanted with an electrode array and drug delivery cannula. BDNF was administered to the implanted cochleae during a 4-week period via a mini-osmotic pump. After completion of the treatment, the osmotic pumps were removed. Two weeks later, the animals were killed and the survival of SGCs was analyzed. To monitor the functionality of the auditory nerve, electrically evoked auditory brainstem responses (eABRs) were recorded in awake animals throughout the experiment. BDNF treatment resulted in enhanced survival of SGCs 2 weeks after cessation of the treatment and prevented the decreases in size and circularity that are seen in the untreated contralateral cochleae. The amplitude of the suprathreshold eABR response in BDNF-treated animals was significantly larger than in deafened control animals and comparable to that in normal-hearing control animals. The amplitude in the BDNF-treated group did not decrease significantly after cessation of treatment. The eABR latency in BDNF-treated animals was longer than normal and comparable to that in deafened control animals. These morphological and functional findings demonstrate that neurotrophic intervention had a lasting effect, which is promising for future clinical application of neurotrophic factors in implanted human cochleae.