Auditory Neurophysiology publications

In auditory cortex of the mustached bat, the FF (F means frequency modulation), dorsal fringe (DF), and ventral fringe (VF) areas consist of “combination-sensitive” neurons tuned to the pair of an emitted biosonar pulse and its echo with a specific delay (best delay: BD). The DF and VF areas are hierarchically at a higher level than the FF area. Focal electric stimulation of the FF area evokes “centrifugal” BD shifts of DF neurons, i.e., shifts away from the BD of the stimulated FF neurons, whereas stimulation of the DF neurons evokes “centripetal” BD shifts of FF neurons, i.e., shifts toward the BD of the stimulated DF neurons. In our current studies, we found that the feedforward projection from FF neurons evokes centrifugal BD shifts of VF neurons, that the feedback projection from VF neurons evokes centripetal BD shifts of FF neurons, that the contralateral projection from DF neurons evokes centripetal BD shifts of DF neurons, and that the centripetal BD shifts evoked by the DF and VF neurons are 2.5 times larger than the centrifugal BD shifts evoked by the FF neurons. The centrifugal BD shifts shape the selective neural representation of a specific target distance, whereas the centripetal BD shifts expand the representation of the selected specific target distance to focus on the processing of the target information at a specific distance. The centrifugal and centripetal BD shifts evoked by the feedforward and feedback projections promote finer analysis of a target at shorter distances.

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.

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.

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.

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.

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.

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.

Any sound can be separated mathematically into a slowly varying envelope and rapidly varying fine-structure component. This property has motivated numerous perceptual studies to understand the relative importance of each component for speech and music perception. Specialized acoustic stimuli, such as auditory chimaeras with the envelope of one sound and fine structure of another have been used to separate the perceptual roles for envelope and fine structure. Cochlear narrowband filtering limits the ability to isolate fine structure from envelope; however, envelope recovery from fine structure has been difficult to evaluate physiologically. To evaluate envelope recovery at the output of the cochlea, neural cross-correlation coefficients were developed that quantify the similarity between two sets of spike-train responses. Shuffled auto- and cross-correlogram analyses were used to compute separate correlations for responses to envelope and fine structure based on both model and recorded spike trains from auditory nerve fibers. Previous correlogram analyses were extended to isolate envelope coding more effectively in auditory nerve fibers with low center frequencies, which are particularly important for speech coding. Recovered speech envelopes were present in both model and recorded responses to one- and 16-band speech fine-structure chimaeras and were significantly greater for the one-band case, consistent with perceptual studies. Model predictions suggest that cochlear recovered envelopes are reduced following sensorineural hearing loss due to broadened tuning associated with outer-hair cell dysfunction. In addition to the within-fiber cross-stimulus cases considered here, these neural cross-correlation coefficients can also be used to evaluate spatiotemporal coding by applying them to cross-fiber within-stimulus conditions. Thus, these neural metrics can be used to quantitatively evaluate a wide range of perceptually significant temporal coding issues relevant to normal and impaired hearing.

Although systems that are involved in attentional selection have been studied extensively, much less is known about nonselective systems. To study these preparatory mechanisms, we compared activity in auditory cortex that was elicited by sounds while rats performed an auditory task ('engaged') with activity that was elicited by identical stimuli while subjects were awake but not performing a task ('passive'). We found that engagement suppressed responses, an effect that was opposite in sign to that elicited by selective attention. In the auditory thalamus, however, engagement enhanced spontaneous firing rates but did not affect evoked responses. These results indicate that neural activity in auditory cortex cannot be viewed simply as a limited resource that is allocated in greater measure as the state of the animal passes from somnolent to passively listening to engaged and attentive. Instead, the engaged condition possesses a characteristic and distinct neural signature in which sound-evoked responses are paradoxically suppressed.

Integration of multimodal information is essential for understanding complex environments. In the auditory system, multisensory integration first occurs in the cochlear nucleus (CN), where auditory nerve and somatosensory pathways converge (Shore, 2005). A unique feature of multisensory neurons is their propensity to receive cross-modal compensation after deafening. Based on our findings that the vesicular glutamate transporters, VGLUT1 and VGLUT2, are differentially associated with auditory nerve and somatosensory inputs to the CN, respectively (Zhou et al., 2007), we examined their relative distributions after unilateral deafening. After unilateral intracochlear injections of kanamycin (1 and 2 weeks), VGLUT1 immunoreactivity (ir) in the magnocellular CN ipsilateral to the cochlear damage was significantly decreased, whereas VGLUT2-ir in regions that receive nonauditory input was significantly increased 2 weeks after deafening. The pathway-specific amplification of VGLUT2 expression in the CN suggests that, in compensatory response to deafening, the nonauditory influence on CN is significantly enhanced. One undesirable consequence of enhanced glutamatergic inputs could be the increased spontaneous rates in CN neurons that occur after hearing loss and that have been proposed as correlates of the phantom auditory sensations commonly called tinnitus.

The specificity of auditory perceptual learning has been taken as an indicator of the likely locus within the brain at which underlying neuronal changes occur. This study examined interaural level difference (ILD) discrimination learning with sinusoidally amplitude modulated (SAM) tones and whether training-induced threshold improvements generalize from one side of auditory space to the other and to an untrained carrier frequency. A novel, dual-staircase adaptive method was adopted that was designed to prevent participants from identifying the nature of the adaptive track. ILD thresholds obtained with this method were compared with a constant-stimulus technique using otherwise identical stimuli. Adaptive thresholds derived from psychometric functions were found to be biased compared to those obtained from reversals. Although adaptive and constant-stimulus procedures appeared to yield different temporal patterns of learning, no global differences were found between them in terms of training outcomes. These data show that ILD discrimination learning with SAM tones does generalize to an untrained carrier frequency but does not generalize across the midline. This implies that the neural substrate for binaural plasticity is found at a relatively high level of the auditory pathway where information is combined across frequency and where each side of auditory space is represented separately.

High doses of salicylate, the anti-inflammatory component of aspirin, induce transient tinnitus and hearing loss. Systemic injection of 250 mg/kg of salicylate, a dose that reliably induces tinnitus in rats, significantly reduced the sound evoked output of the rat cochlea. Paradoxically, salicylate significantly increased the amplitude of the sound-evoked field potential from the auditory cortex (AC) of conscious rats, but not the inferior colliculus (IC). When rats were anesthetized with isoflurane, which increases GABA-mediated inhibition, the salicylate-induced AC amplitude enhancement was abolished, whereas ketamine, which blocks N-methyl-d-aspartate receptors, further increased the salicylate-induced AC amplitude enhancement. Direct application of salicylate to the cochlea, however, reduced the response amplitude of the cochlea, IC and AC, suggesting the AC amplitude enhancement induced by systemic injection of salicylate does not originate from the cochlea. To identify a behavioral correlate of the salicylate-induced AC enhancement, the acoustic startle response was measured before and after salicylate treatment. Salicylate significantly increased the amplitude of the startle response. Collectively, these results suggest that high doses of salicylate increase the gain of the central auditory system, presumably by down-regulating GABA-mediated inhibition, leading to an exaggerated acoustic startle response. The enhanced startle response may be the behavioral correlate of hyperacusis that often accompanies tinnitus and hearing loss.

We investigated the origin of spike frequency adaptation within a layered sensory network: the auditory pathway of locusts. Spike frequency adaptation as observed in an individual neuron may arise because of intrinsic or presynaptic adaptation mechanisms. To separate the contribution of different mechanisms, we recorded from the same cell during acoustic and intracellular current stimulation. We studied three identified neuron types that are representative for each network layer and participate in processing auditory patterns and localizing sound sources. By comparing current and acoustic stimulation, three distinct patterns of the distribution of adaptation mechanisms within the sensory network emerged: (1) balanced influence of both intrinsic and presynaptic adaptation mechanisms in an interneuron that summates over several receptor afferents (TN1), (2) predominantly inhibiting input as the source for spike frequency adaptation in a cell that transmits both pattern representation and directional information (BSN1), (3) primarily intrinsic, spike-triggered adaptation currents within an interneuron coding exclusively for direction (AN2). The time courses of spike frequency adaptation differed significantly between the cells types. Using the adaptation time constants, we were able to predict signal transmission properties for the different cells. We conclude that the adaptation mechanisms differ greatly among interneurons within this sensory pathway and are a function of their role in information processing.

An organism's ability to detect and discriminate sensory inputs depends on the recent stimulus history. For example, perceptual detection thresholds for a brief tone can be elevated by as much as 50 dB when following a masking stimulus. Previous work suggests that such forward masking is not a direct result of peripheral neural adaptation; the central pathway apparently modifies the representation in a way that further attenuates the input's response to short probe signals. Here, we show that much of this transformation is complete by the level of the inferior colliculus (IC). Single-neuron extracellular responses were recorded in the central nucleus of the awake marmoset IC. The threshold for a 20 ms probe tone presented at best frequency was determined for various masker-probe delays, over a range of masker sound pressure levels (SPLs) and frequencies. The most striking aspect of the data was the increased potency of forward maskers as their SPL was increased, despite the fact that the excitatory response to the masker was often saturating or nonmonotonic over the same range of levels. This led to probe thresholds at high masker levels that were almost always higher than those observed in the auditory nerve. Probe threshold shifts were not usually caused by a persistent excitatory response to the masker; instead we propose a wide-dynamic-range inhibitory mechanism locked to sound offset as an explanation for several key aspects of the data. These findings further delineate the role of subcortical auditory processing in the generation of a context-dependent representation of ongoing acoustic scenes.

Because we can perceive the pitch, timbre, and spatial location of a sound source independently, it seems natural to suppose that cortical processing of sounds might separate out spatial from nonspatial attributes. Indeed, recent studies support the existence of anatomically segregated “what” and “where” cortical processing streams. However, few attempts have been made to measure the responses of individual neurons in different cortical fields to sounds that vary simultaneously across spatial and nonspatial dimensions. We recorded responses to artificial vowels presented in virtual acoustic space to investigate the representations of pitch, timbre, and sound source azimuth in both core and belt areas of ferret auditory cortex. A variance decomposition technique was used to quantify the way in which altering each parameter changed neural responses. Most units were sensitive to two or more of these stimulus attributes. Although indicating that neural encoding of pitch, location, and timbre cues is distributed across auditory cortex, significant differences in average neuronal sensitivity were observed across cortical areas and depths, which could form the basis for the segregation of spatial and nonspatial cues at higher cortical levels. Some units exhibited significant nonlinear interactions between particular combinations of pitch, timbre, and azimuth. These interactions were most pronounced for pitch and timbre and were less commonly observed between spatial and nonspatial attributes. Such nonlinearities were most prevalent in primary auditory cortex, although they tended to be small compared with stimulus main effects.

Previous studies have indicated the importance of the spiral ligament (SL) in the pathogenesis of sensorineural hearing loss. The aim of this study was to establish a mouse model for SL degeneration as the basis for the development of new strategies for SL regeneration. We injected 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, at various concentrations into the posterior semicircular canal of adult C57BL/6 mice. Saline-injected animals were used as controls. Auditory function was monitored by measurements of auditory brain stem responses (ABRs). On postoperative day 14, cochlear specimens were obtained after the measurement of the endocochlear potential (EP). Animals that were injected with 5 or 10 mM 3-NP showed a massive elevation of ABR thresholds along with extensive degeneration of the cochleae. Cochleae injected with 1 mM 3-NP exhibited selective degeneration of the SL fibrocytes but alterations in EP levels and ABR thresholds were not of sufficient magnitude to allow for testing functional recovery after therapeutic interventions. Animals injected with 3 mM 3-NP showed a reduction of around 50% in the EP along with a significant loss of SL fibrocytes, although degeneration of spiral ganglion neurons and hair cells was still present in certain regions. These findings indicate that cochleae injected with 3 mM 3-NP may be useful in investigations designed to test the feasibility of new therapeutic manipulations for functional SL regeneration.