Publications using TDT

Spatial and nonspatial auditory processing is hypothesized to occur in parallel dorsal and ventral pathways, respectively. In this study, we tested the spatial and nonspatial sensitivity of auditory neurons in the ventrolateral prefrontal cortex (vPFC), a cortical area in the hypothetical nonspatial pathway. We found that vPFC neurons were modulated significantly by both the spatial and nonspatial attributes of an auditory stimulus. When comparing these responses with those in anterolateral belt region of the auditory cortex, which is hypothesized to be specialized for processing the nonspatial attributes of auditory stimuli, we found that the nonspatial sensitivity of vPFC neurons was poorer, whereas the spatial selectivity was better than anterolateral neurons. Also, the spatial and nonspatial sensitivity of vPFC neurons was comparable with that seen in the lateral intraparietal area, a cortical area that is a part of the dorsal pathway. These data suggest that substantial spatial and nonspatial processing occurs in both the dorsal and ventral pathways.

Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

Ion channels in the degenerin-epithelial sodium channel (DEG-ENaC) family perform diverse functions, including mechanosensation. Here we explored the role of the vertebrate DEG-ENaC protein, acid-sensing ion channel 2 (ASIC2), in auditory transduction. Contributions of ASIC2 to hearing were examined by comparing hearing threshold and noise sensitivity of wild-type and ASIC2 null mice. ASIC2 null mice showed no significant hearing loss, indicating that the ASIC2 was not directly involved in the mechanotransduction of the mammalian cochlea. However, we found that (1) ASIC2 was present in the spiral ganglion (SG) neurons in the adult cochlea and that externally applied protons induced amiloride-sensitive sodium currents and action potentials in SG neurons in vitro , (2) proton-induced responses were greatly reduced in SG neurons obtained from ASIC2 null mice, indicating that activations of ASIC2 contributed a major portion of the proton-induced excitatory response in SG neurons, and (3) ASIC2 null mice were considerably more resistant to noise-induced temporary, but not permanent, threshold shifts. Together, these data suggest that ASIC2 contributes to suprathreshold functions of the cochlea. The presence of ASIC2 in SG neurons could provide sensors to directly convert local acidosis to excitatory responses, therefore offering a cellular mechanism linking hearing losses caused by many enigmatic causes (e.g., ischemia or inflammation of the inner ear) to excitotoxicity.

This paper provides a look at how modulated broad-band noises modulate the thalamic response evoked by brief probe sounds in the awake animal. We demonstrate that noise not only attenuates the response to probe sounds (masking) but also changes the temporal response pattern (scrambling). Two brief probe sounds, a Gaussian noise burst and a brief sinusoidal tone, were presented in silence and in three ongoing noises. The three noises were targeted at activating the auditory system in qualitatively distinct ways. Dynamic ripple noise, containing many random tone-like elements, is targeted at those parts of the auditory system that respond well to tones. International Collegium of Rehabilitative Audiology noise, comprised of the sum of several simultaneous streams of Schroeder-phase speech, is targeted at those parts of the auditory system that respond well to modulated sounds but lack a well defined response to tones. Gaussian noise is targeted at those parts of the auditory system that respond to acoustic energy regardless of modulation. All noises both attenuated and decreased the precise temporal repeatability of the onset response to probe sounds. In addition, the modulated noises induced context-specific changes in the temporal pattern of the response to probe sounds. Scrambling of the temporal response pattern may be a direct neural correlate of the unfortunate experience of being able to hear, but not understand, speech sounds in noisy environments.

Saltatory electric conduction requires clustered voltage-gated sodium channels (VGSCs) at axon initial segments (AIS) and nodes of Ranvier (NR). A dense membrane undercoat is present at these sites, which is thought to be key for the focal accumulation of channels. Here, we prove that βIVΣ1 spectrin, the only βIV spectrin with an actin-binding domain, is an essential component of this coat. Specifically, βIVΣ1 coexists with βIVΣ6 at both AIS and NR, being the predominant spectrin at AIS. Removal of βIVΣ1 alone causes the disappearance of the nodal coat, an increased diameter of the NR, and the presence of dilations filled with organelles. Moreover, in myelinated cochlear afferent fibers, VGSC and ankyrin G clusters appear fragmented. These ultrastructural changes can explain the motor and auditory neuropathies present in βIVΣ1 −/− mice and point to the βIVΣ1 spectrin isoform as a master-stabilizing factor of AIS/NR membranes.

The jamming avoidance response of the weakly electric fish Gymnarchus niloticus relies on determining the sign of the frequency difference (Df) between the fish's own electric organ discharge (EOD) and that of a neighbor, which is achieved by comparing modulations in amplitude (AM) and phase (PM) that result from the summation of their EODs. These two stimulus features are processed in separate pathways that converge in the torus semicircularis on combination-sensitive neurons, many of which are selective for the sign of Df. We recorded extracellular single-unit responses to independent stimulation with AM and PM and combined AM-PM stimulation to determine how sign selectivity is established. Responses to AM and PM frequently summated nonlinearly, leading to sign-selective responses as a result of facilitation to the preferred sign of Df and/or suppression to the nonpreferred sign of Df. Facilitation typically occurred when responses to AM and PM were aligned, whereas suppression typically occurred when they were offset. By experimentally manipulating the degree of alignment between these two responses, we found that the summed response was dependent on their relative timing. In addition, we found a unique class of units that were sensitive to differences in amplitude between two body surfaces. This sensitivity rendered such units immune to the problem of orientation ambiguity, in which the sign selectivity of a single neuron reverses with changes in stimulus orientation. We discuss potential synaptic mechanisms for driving nonlinear responses in these and other combination-sensitive neurons.

Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by ∼50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic (CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear.

Zebra finches ( Taeniopygia guttata ) learn a specific song pattern during a sensitive period of development, after which song changes little or not at all. However, recent studies have demonstrated substantial behavioral plasticity in song behavior during adulthood under a range of conditions. The current experiment examined song behavior of adult zebra finches temporarily deprived of auditory feedback by chronic exposure to loud white noise (WN). Long-term exposure to continuous WN resulted in disruption of song similar to that observed after deafening. When auditory feedback was restored by discontinuing WN, birds were either tutored using tape-recorded playback or housed with adult conspecific tutors. No evidence of learning new tutor syllables was observed, and recovery of pre-WN song patterns was very limited after restoration of hearing. However, many birds did reacquire some aspects of their pretreatment song, suggesting an adult form of learning that may retain some of the initial aspects of sensorimotor acquisition of song in which vocalizations are shaped to match a stored template representation. The failure to learn novel song elements and the modest degree of recovery observed overall suggest a limit on plasticity in adult birds that have acquired species-typical song patterns and may reflect an important species difference between zebra finches and Bengalese finches.

Monaurally deaf people lack the binaural acoustic difference cues in sound level and timing that are needed to encode sound location in the horizontal plane (azimuth). It has been proposed that these people therefore rely on spectral pinna cues of their normal ear to localize sounds. However, the acoustic head-shadow effect (HSE) might also serve as an azimuth cue, despite its ambiguity when absolute sound levels are unknown. Here, we assess the contribution of either cue in the monaural deaf to two-dimensional (2D) sound localization. In a localization test with randomly interleaved sound levels, we show that all monaurally deaf listeners relied heavily on the HSE, whereas binaural control listeners ignore this cue. However, some monaural listeners responded partly to actual sound-source azimuth, regardless of sound level. We show that these listeners extracted azimuth information from their pinna cues. The better monaural listeners were able to localize azimuth on the basis of spectral cues, the better their ability to also localize sound-source elevation. In a subsequent localization experiment with one fixed sound level, monaural listeners rapidly adopted a strategy on the basis of the HSE. We conclude that monaural spectral cues are not sufficient for adequate 2D sound localization under unfamiliar acoustic conditions. Thus, monaural listeners strongly rely on the ambiguous HSE, which may help them to cope with familiar acoustic environments.

Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear-specific proteins cochlin and beta-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131-150 or beta-tectorin 71-90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4(+) T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4(+) T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell-mediated organ-specific autoimmune disorder of the inner ear.

Auditory information can reach the lateral nucleus of the amygdala (LA) through a monosynaptic thalamic projection or a polysynaptic cortical route. The polymodal input from the perirhinal cortex (PR) is a major informational gateway to the LA and nearby structures. Pretraining PR lesions impair fear conditioning to a context, but there have been no reports that they cause deficits in delay conditioning to an auditory cue. The direct subcortical projection to the LA seems sufficient to support delay conditioning to a tone conditional stimulus (CS). We examined the effect of PR lesions on delay conditioning to two different tone conditional stimuli (4 and 22 kHz tones; both 10 sec duration) and two different rat ultrasonic vocalization (USV) conditional stimuli (10 sec of “22 kHz USVs”). The two USV conditional stimuli were multi-call segments that were recorded (digitized at 100 kHz) from two different rats. One USV CS was a continuous sequence of eight calls, and the other was a portion of a continuous sequence of six calls. PR lesions significantly impaired conditioning to both USV conditional stimuli and to the training context but had no significant effect on conditioning to either tone CS. The role of PR in fear conditioning appears not to be determined by whether the conditional stimuli serve as contexts or cues, but instead by the nature or complexity of the stimuli or stimulus configurations. These cue-specific effects of PR lesions are suggested to reflect differences in the stimulus features that are encoded in the two CS pathways to the LA.

It is believed that odor transduction in the mammalian main olfactory system only involves the cAMP-signaling pathway. Here, we report on odor responsiveness in mice with a disrupted cyclic nucleotide-gated (CNG) channel subunit A2. Several odorants, including putative pheromones, can be detected and discriminated by these mice behaviorally. These odors elicit responses in the olfactory epithelium, main olfactory bulb, and olfactory (piriform) cortex of CNGA2 knock-out mice. In addition, responses to odors detected by CNGA2 knock-out mice are relatively insensitive to inhibitors of the cAMP pathway. These results provide strong evidence that cAMP-independent pathways in the main olfactory system of mammals participate in detecting a subset of odors.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

The contention that normally binaural listeners can localize sound under monaural conditions has been challenged by Wightman and Kistler (J. Acoust. Soc. Am. 101:1050-1063, 1997), who found that listeners are almost completely unable to localize virtual sources of sound when sound is presented to only one ear. Wightman and Kistler's results raise the question of whether monaural spectral cues are used by listeners to localize sound under binaural conditions. We have examined the possibility that monaural spectral cues provide useful information regarding sound-source elevation and front-back hemifield when interaural time differences are available to specify sound-source lateral angle. The accuracy with which elevation and front-back hemifield could be determined was compared between a monaural condition and a binaural condition in which a wide-band signal was presented to the near ear and a version of the signal that had been lowpass-filtered at 2.5 kHz was presented to the far ear. It was found that accuracy was substantially greater in the latter condition, suggesting that information regarding sound-source lateral angle is required for monaural spectral cues to elevation and front-back hemifield to be correctly interpreted.

How do cortical neurons represent the acoustic environment? This question is often addressed by probing with simple stimuli such as clicks or tone pips. Such stimuli have the advantage of yielding easily interpreted answers, but have the disadvantage that they may fail to uncover complex or higher-order neuronal response properties. Here, we adopt an alternative approach, probing neuronal responses with complex acoustic stimuli, including animal vocalizations. We used in vivo whole-cell methods in the rat auditory cortex to record subthreshold membrane potential fluctuations elicited by these stimuli. Most neurons responded robustly and reliably to the complex stimuli in our ensemble. Using regularization techniques, we estimated the linear component, the spectrotemporal receptive field (STRF), of the transformation from the sound (as represented by its time-varying spectrogram) to the membrane potential of the neuron. We find that the STRF has a rich dynamical structure, including excitatory regions positioned in general accord with the prediction of the classical tuning curve. However, whereas the STRF successfully predicts the responses to some of the natural stimuli, it surprisingly fails completely to predict the responses to others; on average, only 11% of the response power could be predicted by the STRF. Therefore, most of the response of the neuron cannot be predicted by the linear component, although the response is deterministically related to the stimulus. Analysis of the systematic errors of the STRF model shows that this failure cannot be attributed to simple nonlinearities such as adaptation to mean intensity, rectification, or saturation. Rather, the highly nonlinear response properties of auditory cortical neurons must be attributable to nonlinear interactions between sound frequencies and time-varying properties of the neural encoder.

Focal excess sensory stimulation evokes reorganization of a sensory system. It is usually an expansion of the neural representation of that stimulus resulting from the shifts of the tuning curves (receptive fields) of neurons toward those of the stimulated neurons. The auditory cortex of the mustached bat has an area that is highly specialized for the processing of target-distance information carried by echo delays. In this area, however, reorganization is due to shifts of the delay-tuning curves of neurons away from those of the stimulated cortical neurons. Elimination of inhibition in the target-distance processing area in the auditory cortex by a drug reverses the direction of the shifts in neural tuning curves. Therefore, such unique reorganization in the time domain is due to strong lateral inhibition in the highly specialized area of the auditory cortex.

The term informational masking has traditionally been used to refer to elevations in signal threshold resulting from masker uncertainty. In the present study, the method of constant stimuli was used to obtain complete psychometric functions (PFs) from 44 normal-hearing listeners in conditions known to produce varying amounts of informational masking. The listener’s task was to detect a pure-tone signal in the presence of a broadband noise masker (low masker uncertainty) and in the presence of multitone maskers with frequencies and amplitudes that varied at random from one presentation to the next (high masker uncertainty). Relative to the broadband noise condition, significant reductions were observed in both the slope and the upper asymptote of the PF for multitone maskers producing large amounts of informational masking. Slope was affected more for some listeners and conditions while asymptote was affected more for others; consequently, neither parameter alone was highly predictive of individual thresholds or the amount of informational masking. Mean slopes and asymptotes varied nonmonotonically with the number of masker components in a manner similar to mean thresholds, particularly when the estimated effect of energetic masking on thresholds was subtracted out. As in past studies, the threshold data were well described by a model in which trial-by-trial judgments are based on a weighted sum of levels in dB at the output of independent auditory filters. The psychometric data, however, complicated the model’s interpretation in two ways: First, they suggested that, depending on the listener and condition, the weights can either reflect a fixed influence of masker components on each trial or the effect of occasionally mistaking a masker component for the signal from trial to trial. Second, they indicated that in either case the variance of the underlying decision variable as estimated from PF slope is not by itself great enough to account for the observed changes in informational masking.

The strength of the acoustic startle reflex (ASR) as a function of age was studied in adult C57BL/6J and CBA/CaJ mice, because altered ASR levels are a potential behavioral consequence of the neural reorganization that accompanies the early-onset hearing loss of the C57BL, in contrast to the normal-hearing CBA. For C57BL mice at 14-36 weeks of age, compared with 7-week-old mice, high-frequency thresholds measured with the auditory brainstem response (ABR) were less sensitive by about 25-30 dB while the hearing loss at low frequencies was 10-15 dB, but by 60 weeks losses of 45-50 dB were present across the entire spectrum. Their ASR amplitudes for 16 kHz tone pips were highest at 7 weeks and then declined with age, but, for 4 kHz tones the ASR increased in strength at 18 weeks and beyond to levels above that of the younger mice. This hyperreactivity persisted even in 60-week-old mice. The ASR for 16 kHz stimuli was positively correlated with hearing sensitivity, but the ASR for 4 kHz stimuli was positively correlated with hearing loss for mice that were 18-36 weeks of age. Furthermore, ASR amplitudes for 4 kHz stimuli were positively correlated with the 16 kHz ASR in young C57BL mice but negatively correlated in older mice. There were no similar ASR or ABR changes in adult CBA mice through 19 weeks of age. Correlations between ASR and ABR scores were always weakly positive, and correlations between 4 kHz and 16 kHz ASR amplitudes were always strongly positive. The ASR data in older C57BL mice with hearing loss are consistent with reports describing their increased neural representation of low-frequency sounds and reinforce the value of this strain for studying the functional consequences that accompany age-related cochlear degeneration.

The present study aimed to examine the effect of noise on vowel-like suprathreshold discrimination in cochlear-implant listeners. The task was to detect an increment in level at the middle harmonic (400 Hz) in the background of a seven-harmonic complex from 100 to 700 Hz in 100-Hz steps. The task was performed in the absence (control) and presence of a white noise presented over a 20-35-dB range from inaudible to loud. The present result shows that discrimination of suprathreshold harmonic stimuli was significantly enhanced, particularly at the soft signal level, with suprathreshold noise. This result suggests that tuning of the noise level is required to optimize performance of different tasks in cochlear implants.