Auditory Neurophysiology publications

Neurons in the superior paraolivary nucleus (SPON) of the rat respond to the offset of pure tones with a brief burst of spikes. Medial nucleus of the trapezoid body (MNTB) neurons, which inhibit the SPON, produce a sustained pure tone response followed by an offset response characterized by a period of suppressed spontaneous activity. This MNTB offset response is duration dependent and critical to the formation of SPON offset spikes [Kadner A, Kulesza RJ Jr, Berrebi AS (2006) Neurons in the medial nucleus of the trapezoid body and superior paraolivary nucleus of the rat may play a role in sound duration coding. J Neurophysiol. 95:1499-1508; Kulesza RJ Jr, Kadner A, Berrebi AS (2007) Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 97:1610-1620]. Here we examine the temporal resolution of the rat's MNTB/SPON circuit by assessing its capability to i) detect gaps in tones, and ii) synchronize to sinusoidally amplitude modulated (SAM) tones. Gap detection was tested by presenting two identical pure tone markers interrupted by gaps ranging from 0 to 25 ms duration. SPON neurons responded to the offset of the leading marker even when the two markers were separated only by their ramps (i.e. a 0 ms gap); longer gap durations elicited progressively larger responses. MNTB neurons produced an offset response at gap durations of 2 ms or longer, with a subset of neurons responding to 0 ms gaps. SAM tone stimuli used the unit's characteristic frequency as a carrier, and modulation rates ranged from 40 to 1160 Hz. MNTB neurons synchronized to modulation rates up to approximately 1 kHz, whereas spiking of SPON neurons decreased sharply at modulation rates >or=400 Hz. Modulation transfer functions based on spike count were all-pass for MNTB neurons and low-pass for SPON neurons; the modulation transfer functions based on vector strength were low-pass for both nuclei, with a steeper cutoff for SPON neurons. Thus, the MNTB/SPON circuit encodes episodes of low stimulus energy, such as gaps in pure tones and troughs in amplitude modulated tones. The output of this circuit consists of brief SPON spiking episodes; their potential effects on the auditory midbrain and forebrain are discussed.

Learning modifies the primary auditory cortex (A1) to emphasize the processing and representation of behaviorally relevant sounds. However, the factors that determine cortical plasticity are poorly understood. While the type and amount of learning are assumed to be important, the actual strategies used to solve learning problems might be critical. To investigate this possibility, we trained two groups of adult male Sprague-Dawley rats to bar-press (BP) for water contingent on the presence of a 5.0 kHz tone using two different strategies: BP during tone presence or BP from tone-onset until receiving an error signal after tone cessation. Both groups achieved the same high levels of correct performance and both groups revealed equivalent learning of absolute frequency during training. Post-training terminal "mapping" of A1 showed no change in representational area of the tone signal frequency but revealed other substantial cue-specific plasticity that developed only in the tone-onset-to-error strategy group. Threshold was decreased approximately 10 dB and tuning bandwidth was narrowed by approximately 0.7 octaves. As sound onsets have greater perceptual weighting and cortical discharge efficacy than continual sound presence, the induction of specific learning-induced cortical plasticity may depend on the use of learning strategies that best exploit cortical proclivities. The present results also suggest a general principle for the induction and storage of plasticity in learning, viz., that the representation of specific acquired information may be selected by neurons according to a match between behaviorally selected stimulus features and circuit/network response properties.

How do neuronal populations in the auditory cortex represent acoustic stimuli? Although sound-evoked neural responses in the anesthetized auditory cortex are mainly transient, recent experiments in the unanesthetized preparation have emphasized subpopulations with other response properties. To quantify the relative contributions of these different subpopulations in the awake preparation, we have estimated the representation of sounds across the neuronal population using a representative ensemble of stimuli. We used cell-attached recording with a glass electrode, a method for which single-unit isolation does not depend on neuronal activity, to quantify the fraction of neurons engaged by acoustic stimuli (tones, frequency modulated sweeps, white-noise bursts, and natural stimuli) in the primary auditory cortex of awake head-fixed rats. We find that the population response is sparse, with stimuli typically eliciting high firing rates (>20 spikes/second) in less than 5% of neurons at any instant. Some neurons had very low spontaneous firing rates (<0.01 spikes/second). At the other extreme, some neurons had driven rates in excess of 50 spikes/second. Interestingly, the overall population response was well described by a lognormal distribution, rather than the exponential distribution that is often reported. Our results represent, to our knowledge, the first quantitative evidence for sparse representations of sounds in the unanesthetized auditory cortex. Our results are compatible with a model in which most neurons are silent much of the time, and in which representations are composed of small dynamic subsets of highly active neurons.

In the mustached bat's inferior colliculus (IC), combination-sensitive neurons display time-sensitive facilitatory interactions between inputs tuned to distinct spectral elements in sonar or social vocalizations. Here we compare roles of ionotropic receptors to glutamate (iGluRs), glycine (GlyRs), and GABA (GABA A Rs) in facilitatory combination-sensitive interactions. Facilitatory responses to 36 single IC neurons were recorded before, during, and after local application of antagonists to these receptors. The NMDA receptor antagonist CPP [(±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid], alone ( n = 14) or combined with AMPA receptor antagonist NBQX ( n = 22), significantly reduced or eliminated responses to best frequency (BF) sounds across a broad range of sound levels, but did not eliminate combination-sensitive facilitation. In a subset of neurons, GABA A R blockers bicuculline or gabazine were applied in addition to iGluR blockers. GABA A R blockers did not “uncover” residual iGluR-mediated excitation, and only rarely eliminated facilitation. In nearly all neurons for which the GlyR antagonist strychnine was applied in addition to iGluR blockade (22 of 23 neurons, with or without GABA A R blockade), facilitatory interactions were eliminated. Thus, neither glutamate nor GABA neurotransmission are required for facilitatory combination-sensitive interactions in IC. Instead, facilitation may depend entirely on glycinergic inputs that are presumed to be inhibitory. We propose that glycinergic inputs tuned to two distinct spectral elements in vocal signals each activate postinhibitory rebound excitation. When rebound excitations from two spectral elements coincide, the neuron discharges. Excitation from glutamatergic inputs, tuned to the BF of the neuron, is superimposed onto this facilitatory interaction, presumably mediating responses to a broader range of acoustic signals.

The neural computations that underlie the processing of auditory-stimulus identity are not well understood, especially how information is transformed across different cortical areas. Here, we compared the capacity of neurons in the superior temporal gyrus (STG) and the ventrolateral prefrontal cortex (vPFC) to code the identity of an auditory stimulus; these two areas are part of a ventral processing stream for auditory-stimulus identity. Whereas the responses of neurons in both areas are reliably modulated by different vocalizations, STG responses code significantly more vocalizations than those in the vPFC. Together, these data indicate that the STG and vPFC differentially code auditory identity, which suggests that substantial information processing takes place between these two areas. These findings are consistent with the hypothesis that the STG and the vPFC are part of a functional circuit for auditory-identity analysis.

Gonadectomized and intact adult C57BL/6J (B6) mice of both sexes were exposed for 12h nightly to an augmented acoustic environment (AAE): repetitive bursts of a 70dB SPL noise band. The high-frequency AAE (HAAE) was a half-octave band centered at 20kHz; the low-frequency AAE (LAAE) was a 2-8kHz band. The effects of sex, gonadectomy, and AAE treatment on genetic progressive hearing loss (a trait of B6 mice) were evaluated by obtaining auditory brainstem response (ABR) thresholds at ages 3-, 6-, and 9-months. At 9-months of age, hair cell counts (cytocochleograms) were obtained, and morphometric measures of the anteroventral cochlear nucleus (AVCN) were obtained. LAAE treatment caused elevation in ABR thresholds (8-24kHz), with the highest thresholds occurring in intact females. LAAE treatment caused some loss of outer hair cells in the basal half of the cochlea (in addition to losses normally occurring in B6 mice), with intact females losing more cells than intact males. The loss of AVCN neurons and shrinkage of tissue volume that typically occur in 9-month-old B6 mice was lessened by LAAE treatment in intact (but not gonadectomized) male mice, whereas the degenerative changes were exacerbated in intact (but not gonadectomized) females. These LAAE effects were prominent in, but not restricted to, the tonotopic low-frequency (ventral) AVCN. HAAE treatment resulted in some loss of neurons in the high-frequency (dorsal) AVCN. In general, LAAE treatment plus male gonadal hormones (intact males) had an ameliorative effect whereas HAAE or LAAE treatment plus ovarian hormones (intact females) had a negative effect on age-related changes in the B6 auditory system.

The multichannel design of contemporary cochlear implants (CIs) is predicated on the assumption that each channel activates a relatively restricted and independent sector of the deaf auditory nerve array, just as a sound within a restricted frequency band activates a restricted region of the normal cochlea The independence of CI channels, however, is limited; and the factors that determine their independence, the relative overlap of the activity patterns that they evoke, are poorly understood. In this study, we evaluate the spread of activity evoked by cochlear implant channels by monitoring activity at 16 sites along the tonotopic axis of the guinea pig inferior colliculus (IC). "Spatial tuning curves" (STCs) measured in this way serve as an estimate of activation spread within the cochlea and the ascending auditory pathways. We contrast natural stimulation using acoustic tones with two kinds of electrical stimulation either (1) a loose fitting banded array consisting of a cylindrical silicone elastomer carrier with a linear series of ring contacts; or (2) a space-filling array consisting of a tapered silicone elastomer carrier that is designed to fit snugly into the guinea pig scala tympani with a linear series of ball contacts positioned along it Spatial tuning curves evoked by individual acoustic tones, and by activation of each contact of each array as a monopole, bipole or tripole were recorded. Several channel configurations and a wide range of electrode separations were tested for each array, and their thresholds and selectivity were estimated. The results indicate that the tapered space-filling arrays evoked more restricted activity patterns at lower thresholds than did the banded arrays. Monopolar stimulation (one intracochlear contact activated with an extracochlear return) using either array evoked broad activation patterns that involved the entire recording array at current levels <6dBSL, but at relatively low thresholds. Bi- and tri-polar configurations of both array types evoked more restricted activity patterns, but their thresholds were higher than those of monopolar configurations. Bipolar and tripolar configurations with closely spaced contacts evoked activity patterns that were comparable to those evoked by pure tones. As the spacing of bipolar electrodes was increased (separations >1mm), the activity patterns became broader and evoked patterns with two distinct threshold minima, one associated with each contact.

The basic helix-loop-helix (bHLH) transcription factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) and optic nerve development. Using Math5-lacZ knockout mice, we have identified an additional expression domain for Math5 outside the eye, in functionally connected structures of the central auditory system. In the adult hindbrain, the cytoplasmic Math5-lacZ reporter is expressed within the ventral cochlear nucleus (VCN), in a subpopulation of neurons that project to medial nucleus of the trapezoid body (MNTB), lateral superior olive (LSO), and lateral lemniscus (LL). These cells were identified as globular and small spherical bushy cells based on their morphology, abundance, distribution within the cochlear nucleus (CN), co-expression of Kv1.1, Kv3.1b and Kcnq4 potassium channels, and projection patterns within the auditory brainstem. Math5-lacZ is also expressed by cochlear root neurons in the auditory nerve. During embryonic development, Math5-lacZ was detected in precursor cells emerging from the caudal rhombic lip from embryonic day (E)12 onwards, consistent with the time course of CN neurogenesis. These cells co-express MafB and are post-mitotic. Math5 expression in the CN was verified by mRNA in situ hybridization, and the identity of positive neurons was confirmed morphologically using a Math5-Cre BAC transgene with an alkaline phosphatase reporter. The hindbrains of Math5 mutants appear grossly normal, with the exception of the CN. Although overall CN dimensions are unchanged, the lacZ-positive cells are significantly smaller in Math5 -/- mice compared to Math5 +/- mice, suggesting these neurons may function abnormally. The auditory brainstem response (ABR) of Math5 mutants was evaluated in a BALB/cJ congenic background. ABR thresholds of Math5 -/- mice were similar to those of wild-type and heterozygous mice, but the interpeak latencies for Peaks II-IV were significantly altered. These temporal changes are consistent with a higher-level auditory processing disorder involving the CN, potentially affecting the integration of binaural sensory information.

Cochlear implant surgery is currently the therapy of choice for profoundly deaf patients. However, the functionality of cochlear implants depends on the integrity of the auditory spiral ganglion neurons. This study assesses the combined efficacy of two classes of agents found effective in preventing degeneration of the auditory nerve following deafness, neurotrophic factors, and antioxidants. Guinea pigs were deafened and treated for 4 weeks with either local administration of GDNF or a combination of GDNF and systemic injections of the antioxidants ascorbic acid and Trolox. The density of surviving spiral ganglion cells was significantly enhanced and the thresholds for eliciting an electrically evoked brain stem response were significantly reduced in GDNF treated animals compared to deafened-untreated. The addition of antioxidants significantly enhanced the evoked responsiveness over that observed with GDNF alone. The results suggest multiple sites of intervention in the rescue of these cells from deafferentation-induced cell death.

Multisensory neurons in the dorsal cochlear nucleus (DCN) achieve their bimodal response properties [Shore (2005) Eur. J. Neurosci. , 21 , 3334–3348] by integrating auditory input via VIIIth nerve fibers with somatosensory input via the axons of cochlear nucleus granule cells [Shore et al. (2000) J. Comp. Neurol. , 419 , 271–285; Zhou & Shore (2004) J. Neurosci. Res. , 78 , 901–907]. A unique feature of multisensory neurons is their propensity for receiving cross‐modal compensation following sensory deprivation. Thus, we investigated the possibility that reduction of VIIIth nerve input to the cochlear nucleus results in trigeminal system compensation for the loss of auditory inputs. Responses of DCN neurons to trigeminal and bimodal (trigeminal plus acoustic) stimulation were compared in normal and noise‐damaged guinea pigs. The guinea pigs with noise‐induced hearing loss had significantly lower thresholds, shorter latencies and durations, and increased amplitudes of response to trigeminal stimulation than normal animals. Noise‐damaged animals also showed a greater proportion of inhibitory and a smaller proportion of excitatory responses compared with normal. The number of cells exhibiting bimodal integration, as well as the degree of integration, was enhanced after noise damage. In accordance with the greater proportion of inhibitory responses, bimodal integration was entirely suppressive in the noise‐damaged animals with no indication of the bimodal enhancement observed in a sub‐set of normal DCN neurons. These results suggest that projections from the trigeminal system to the cochlear nucleus are increased and/or redistributed after hearing loss. Furthermore, the finding that only neurons activated by trigeminal stimulation showed increased spontaneous rates after cochlear damage suggests that somatosensory neurons may play a role in the pathogenesis of tinnitus.

Objectives: The objective of this study was to describe the cortical evoked response to silent gaps in a group of young adults with normal hearing using stimulus conditions identical to those used in psychophysical studies of gap detection. Specifically, we sought to examine the P1-N1-P2 auditory evoked response to the onsets of stimuli (markers) defining a silent gap for within-channel (spectrally identical markers) and across-channel (spectrally different markers) conditions using four perceptually-equated gap durations. It was hypothesized that (1) P1, N1, and P2 would be present and consistent for 1st marker (before the gap) onsets; (2) for within-channel markers, P1, N1, and P2 would be present for 2nd marker (after the gap) onsets only when the gap was of a duration equal to or larger than the behaviorally measured gap detection threshold; and (3) for the across-channel conditions, P1, N1, and P2 would be present for 2nd marker onsets regardless of gap duration. This is expected due to the additional cue of frequency change following the gap. Design: Twelve young adults (mean age 26 years) with normal hearing participated. Within-channel and across-channel gap detection thresholds were determined using an adaptive psychophysical procedure. Next, cortical auditory evoked potentials (P1-N1-P2) were recorded with a 32-channel Neuroscan electroencephalogram system using within-channel and across-channel markers identical to those used for the psychophysical task and four perceptually weighted gap durations: (1) individual listener's gap detection threshold; (2) above gap detection threshold; (3) below gap detection threshold; and (4) a 1-ms gap identical to the gap in the standard interval of the psychophysical task. P1-N1-P2 peak latencies and amplitudes were analyzed using repeated-measures analyses of variance. A temporal-spatial principal component analysis was also conducted. Results: The latency of P2 and the amplitude of P1, N1, and P2 were significantly affected by the acoustic characteristics of the 2nd marker as well as the duration of the gap. Larger amplitudes and shorter latencies were generally found for the conditions in which the acoustic cues were most salient (e.g., across-channel markers, 1st markers, large gap durations). Interestingly, the temporal-spatial principal component analysis revealed activity elicited by gap durations equal to gap detection threshold in the latency regions of 167 and 183 ms for temporal-parietal and right-frontal spatial locations. Conclusions: The cortical response to a silent gap is unique to specific marker characteristics and gap durations among young adults with normal hearing. Specifically, when the onset of the 2nd marker is perceptually salient, the amplitude of the P1-N1-P2 response is relatively larger and the P2 latency is relatively shorter than for nonsalient 2nd marker onsets, providing noninvasive, nonbehavioral indicators of the neural coding of this important temporal cue in the thalamic-cortical region of the central auditory system. Gap duration appears to be most clearly indicated by P1 and T-complex amplitude.

We have identified a novel nucleus of the mammalian brain and termed it the tectal longitudinal column (TLC). Basic histologic stains, tract-tracing techniques and three-dimensional reconstructions reveal that the rat TLC is a narrow, elongated structure spanning the midbrain tectum longitudinally. This paired nucleus is located close to the midline, immediately dorsal to the periaqueductal gray matter. It occupies what has traditionally been considered the most medial region of the deep superior colliculus and the most medial region of the inferior colliculus. The TLC differs from the neighboring nuclei of the superior and inferior colliculi and the periaqueductal gray by its distinct connections and cytoarchitecture. Extracellular electrophysiological recordings show that TLC neurons respond to auditory stimuli with physiologic properties that differ from those of neurons in the inferior or superior colliculi. We have identified the TLC in rodents, lagomorphs, carnivores, nonhuman primates, and humans, which indicates that the nucleus is conserved across mammals. The discovery of the TLC reveals an unexpected level of longitudinal organization in the mammalian tectum and raises questions as to the participation of this mesencephalic region in essential, yet completely unexplored, aspects of multisensory and/or sensorimotor integration.

Perception of complex sounds depends on the encoding of the dynamic and static structures within the ongoing stimulus by the auditory system. Aging has been associated with deficits in both areas, thus, the difficulty that the elderly have in speech comprehension could due to hearing loss, or to a loss of temporal sensitivity, or some combination of both. We investigated the effects of sensorineural hearing loss (SNHL) on neural correlates of temporal resolution by recording the responses of inferior colliculus neurons to a gap detection paradigm. We used C57BL/6 (C57) strain of laboratory mouse, which carries the Ahl deafness gene that initiates a progressive high frequency SNHL beginning at about 2 months of age and rapidly progresses to total deafness by 18 months. We compared gap encoding from inferior collicular neurons from young, normal-hearing C57 mice and middle-aged, hearing-impaired, C57 mice, quantifying minimal gap threshold, and recovery functions. The proportion of unit types, spontaneous rates and degree of monotonicity were comparable between young and middle-aged C57 mice. As expected, single unit thresholds were elevated by 30-40 dB in middle-aged C57 mice. However, no significant differences in mean minimal gap thresholds or in the slopes of the gap recovery functions were found between the two age groups. Thus, the results suggest that moderate high frequency SNHL does not affect temporal processing as measured by the gap detection paradigm.

The clawed frog Xenopus laevis produces vocalizations consisting of distinct patterns of clicks. This study provides the first description of spontaneous, pure-tone and communication-signal evoked discharge properties of auditory nerve (n.VIII) fibers and dorsal medullary nucleus (DMN) cells in an obligatorily aquatic anuran. Responses of 297 n.VIII and 253 DMN units are analyzed for spontaneous rates (SR), frequency tuning, rate-intensity functions, and firing rate adaptation, with a view to how these basic characteristics shape responses to recorded call stimuli. Response properties generally resemble those in partially terrestrial anurans. Broad tuning exists across characteristic frequencies (CFs). Threshold minima are -101 dB re 1 mm/s at 675 Hz; -87 dB at 1,600 Hz; and -61 dB at 3,000 Hz (-90, -77, and -44 dB re 1 Pa, respectively), paralleling the peak frequency of vocalizations at 1.2-1.6 kHz with approximately 500 Hz in 3 dB bandwidth. SRs range from 0 to 80 (n.VIII) and 0 to 73 spikes/s (DMN). Nerve and DMN units of all CFs follow click rates in natural calls, < or =67 clicks/s and faster. Units encode clicks with a single spike, double spikes, or bursts. Spike times correlate closely with click envelopes. No temporal filtering for communicative click rates occurs in either n.VIII or the DMN.

The ascending and descending projections of the central auditory system form multiple tonotopic loops. This study specifically examines the tonotopic pathway from the auditory thalamus to the auditory cortex and then to the auditory midbrain in mice. We observed the changes of receptive fields in the central nucleus of the inferior colliculus of the midbrain evoked by focal electrical stimulation of the ventral division of the medial geniculate body of the thalamus. The receptive field of an auditory neuron was characterized by five parameters: the best frequency, minimum threshold, bandwidth, size of receptive field, and average spike number. We found that focal thalamic stimulation changed the parametric values characterizing the recorded collicular receptive fields toward those characterizing the stimulated thalamic receptive fields. Cortical inactivation with muscimol prevented the development of the collicular plasticity induced by focal thalamic stimulation. Our data suggest that the intact colliculo-thalamo-cortico-collicular loops are important for the coordination of sound-guided plasticity in the central auditory system.

The spectral, temporal, and intensive selectivity of neurons in the adult primary auditory cortex (A1) is easily degraded in early postnatal life by raising rat pups in the presence of pulsed noise. The nonselective frequency tuning recorded in these rats substantially endures into adulthood. Here we demonstrate that perceptual training applied in these developmentally degraded postcritical-period rats results in the recovery of normal representational fidelity. By using a modified go/no-go training strategy, structured noise-reared rats were trained to identify target auditory stimuli of specific frequency from a set of distractors varying in frequency. Target stimuli changed daily on a random schedule. Consistent with earlier findings, structured noise exposure within the critical period resulted in disrupted tonotopicity within A1 and in degraded frequency-response selectivity for A1 neurons. Tonotopicity and frequency-response selectivity were normalized by perceptual training. Changes induced by training endured without loss for at least 2 months after training cessation. The results further demonstrate the potential utility of perceptual learning as a strategy for normalizing deteriorated auditory representations in older (postcritical-period) children and adults.

Space-specific neurons in the barn owl's auditory space map gain spatial selectivity through tuning to combinations of the interaural time difference (ITD) and interaural level difference (ILD). The combination of ITD and ILD in the subthreshold responses of space-specific neurons in the external nucleus of the inferior colliculus (ICx) is well described by a multiplication of ITD- and ILD-dependent components. It is unknown, however, how ITD and ILD are combined at the site of ITD and ILD convergence in the lateral shell of the central nucleus of the inferior colliculus (ICcl) and therefore whether ICx is the first site in the auditory pathway where multiplicative tuning to ITD- and ILD-dependent signals occurs. We used extracellular recording of single neurons to determine how ITD and ILD are combined in ICcl of the anesthetized barn owl ( Tyto alba). A comparison of additive, multiplicative, and linear-threshold models of neural responses shows that ITD and ILD are combined nonlinearly in ICcl, but the interaction of ITD and ILD is not uniformly multiplicative over the sample. A subset (61%) of the neural responses is well described by the multiplicative model, indicating that ICcl is the first site where multiplicative tuning to ITD- and ILD-dependent signals occurs. ICx, however, is the first site where multiplicative tuning is observed consistently. A network model shows that a linear combination of ICcl responses to ITD–ILD pairs is sufficient to produce the multiplicative subthreshold responses to ITD and ILD seen in ICx.

Although the auditory cortex is known to be essential for normal sound localization in the horizontal plane, its contribution to vertical localization has not so far been examined. In this study, we measured the acuity with which ferrets could discriminate between two speakers in the midsagittal plane before and after silencing activity bilaterally in the primary auditory cortex (A1). This was achieved either by subdural placement of Elvax implants containing the GABA A receptor agonist muscimol or by making aspiration lesions after determining the approximate location of A1 electrophysiologically. Psychometric functions and minimum audible angles were measured in the upper hemifield for 500-, 200-, and 40-ms noise bursts. Muscimol-Elvax inactivation of A1 produced a small but significant deficit in the animals’ ability to localize brief (40-ms) sounds, which was reversed after removal of the Elvax implants. A similar deficit in vertical localization was observed after bilateral aspiration lesions of A1, whereas performance at longer sound durations was unaffected. Another group of ferrets received larger lesions, encompassing both primary and nonprimary auditory cortical areas, and showed a greater deficit with performance being impaired for long- and short-duration (500- and 40-ms, respectively) stimuli. These data suggest that the integrity of the auditory cortex is required to successfully utilize spectral localization cues, which are thought to provide the basis for vertical localization, and that multiple cortical fields, including A1, contribute to this task.

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.