The role of broadband inhibition in the rate representation of spectral cues for sound localization in the inferior colliculus

Previous investigations have shown that a subset of inferior colliculus neurons, which have been designated type O units, respond selectively to isolated features of the cat's head-related transfer functions (HRTFs: the directional transformation of a free-field sound as it propagates from the head to the eardrum). Based on those results, it was hypothesized that type O units would show enhanced spatial tuning in a virtual sound field that conveyed the full complement of HRTF-based localization cues. As anticipated, a number of neurons produced representations of virtual sound source locations that were spatially tuned, level tolerant, and effective under monaural conditions. Preferred locations were associated with spectral cues that complemented the highly individualized broadband inhibitory patterns of tuned neurons. That is, higher response magnitudes were achieved when spectral peaks coincided with excitatory influences at best frequency (BF: the most sensitive frequency) and spectral notches fell within flanking inhibitory regions. The directionally dependent modulation of narrowband ON-BF excitation by broadband OFF-BF inhibition was not a unique property of type O units.     

Contralateral Effects and Binaural Interactions in Dorsal Cochlear Nucleus

The dorsal cochlear nucleus (DCN) receives afferent input from the auditory nerve and is thus usually thought of as a monaural nucleus, but it also receives inputs from the contralateral cochlear nucleus as well as descending projections from binaural nuclei. Evidence suggests that some of these commissural and efferent projections are excitatory, whereas others are inhibitory. The goals of this study were to investigate the nature and effects of these inputs in the DCN by measuring DCN principal cell (type IV unit) responses to a variety of contralateral monaural and binaural stimuli. As expected, the results of contralateral stimulation demonstrate a mixture of excitatory and inhibitory influences, although inhibitory effects predominate. Most type IV units are weakly, if at all, inhibited by tones but are strongly inhibited by broadband noise (BBN). The inhibition evoked by BBN is also low threshold and short latency. This inhibition is abolished and excitation is revealed when strychnine, a glycine-receptor antagonist, is applied to the DCN; application of bicuculline, a GABA_A-receptor antagonist, has similar effects but does not block the onset of inhibition. Manipulations of discrete fiber bundles suggest that the inhibitory, but not excitatory, inputs to DCN principal cells enter the DCN via its output pathway, and that the short latency inhibition is carried by commissural axons. Consistent with their respective monaural effects, responses to binaural tones as a function of interaural level difference are essentially the same as responses to ipsilateral tones, whereas binaural BBN responses decrease with increasing contralateral level. In comparison to monaural responses, binaural responses to virtual space stimuli show enhanced sensitivity to the elevation of a sound source in ipsilateral space but reduced sensitivity in contralateral space. These results show that the contralateral inputs to the DCN are functionally relevant in natural listening conditions, and that one role of these inputs is to enhance DCN processing of spectral sound localization cues produced by the pinna.     

Role of the dorsal cochlear nucleus in the sound localization behavior of cats

The role of the dorsal cochlear nucleus (DCN) in directional hearing was evaluated by measuring sound localization behaviors before and after cats received lesions of the dorsal and intermediate acoustic striae (DAS/IAS). These lesions are presumed to disrupt spectral processing in the DCN without affecting binaural time and level difference cues that exit the cochlear nucleus via the ventral acoustic stria. Prior to DAS/IAS lesions, cats made accurate head orientation responses toward sound sources in the frontal sound field. After a unilateral DAS/IAS lesion, subjects showed increased errors in the azimuth and elevation of their responses; in addition, the final orientation of head movements tended to be more variable. Largest deficits in response elevation were observed in the hemifield that was ipsilateral to the lesion. When a second lesion was placed in the opposite DAS/IAS, increased orientation errors were observed throughout the frontal field. Nonetheless, bilaterally lesioned cats showed normal discrimination of changes in sound source location when tested with a spatial acuity task. These findings support previous interpretations that the DCN contributes to sound orientation behavior, and further suggest that the identification of absolute sound source locations and the discrimination between spatial locations involve independent auditory processing mechanisms.     

Excitatory and facilitatory frequency response areas in the inferior colliculus of the mustached bat

In the mustached bat's central nucleus of the inferior colliculus (ICC), many neurons display facilitatory or inhibitory responses when presented with two tones of distinctly different frequencies. Our previous studies have focused on spectral interactions between specific frequency bands contained in the bat's sonar vocalization. In this study, we describe excitatory and facilitatory frequency response areas across all frequencies in the mustached bat's audible range. We show that many neurons in the ICC have more extensive frequency interactions than previously documented. We recorded responses of 96 single units to single tones and combinations of two tones. Best frequencies of the units ranged from 59-15 kHz. Forty-one units had a single, excitatory frequency response area. The rest of the units had more complex frequency tuning that included multiple excitatory frequency response areas and facilitatory frequency response areas. Some of the facilitatory frequency interactions were between one sound with energy in a sonar frequency band and a second sound with energy in a non-sonar frequency band. We also found that neurons could be facilitated by more than one additional frequency band. Our findings of extensive frequency interactions in the ICC of the mustached bat suggest that some neurons may be well suited for the analysis of complex sounds, possibly including social communication sounds.     

Effects of Signal Level and Background Noise on Spectral Representations in the Auditory Nerve of the Domestic Cat

Background noise poses a significant obstacle for auditory perception, especially among individuals with hearing loss. To better understand the physiological basis of this perceptual impediment, the present study evaluated the effects of background noise on the auditory nerve representation of head-related transfer functions (HRTFs). These complex spectral shapes describe the directional filtering effects of the head and torso. When a broadband sound passes through the outer ear en route to the tympanic membrane, the HRTF alters its spectrum in a manner that establishes the perceived location of the sound source. HRTF-shaped noise shares many of the acoustic features of human speech, while communicating biologically relevant localization cues that are generalized across mammalian species. Previous studies have used parametric manipulations of random spectral shapes to elucidate HRTF coding principles at various stages of the cat’s auditory system. This study extended that body of work by examining the effects of sound level and background noise on the quality of spectral coding in the auditory nerve. When fibers were classified by their spontaneous rates, the coding properties of the more numerous low-threshold, high-spontaneous rate fibers were found to degrade at high presentation levels and in low signal-to-noise ratios. Because cats are known to maintain accurate directional hearing under these challenging listening conditions, behavioral performance may be disproportionally based on the enhanced dynamic range of the less common high-threshold, low-spontaneous rate fibers.     

On the Role of the Wideband Inhibitor in the Dorsal Cochlear Nucleus: A Computational Modeling Study

Principal cells (type IV units) in the dorsal cochlear nucleus (DCN) are uniquely sensitive to (are inhibited by) energy minima or notches in acoustic spectra, which provide cues to sound localization. The once accepted conceptual model of the DCN suggested that this sensitivity was shaped largely by inhibitory inputs from wideband inhibitors (WBIs), which received auditory nerve inputs over a wide frequency range and inhibited type IV units over a narrow frequency range. A computational model based on this wide-input narrow-output conceptual model was able to reproduce quantitatively type IV unit responses to notch-noise stimuli as a function of notch width. Recent physiological results have shown however that WBIs are unresponsive to notch-noise stimuli with wide notch widths and thus have narrower auditory nerve fiber input bandwidths than previously assumed. A computational model based on a narrow-input narrow-output model of the WBI was unable to account fully for the notch sensitivity of type IV units suggesting the need to add a new component to the DCN circuit. The goal of this study was to test whether making the output bandwidth of the WBIs wide while keeping their input bandwidth narrow could explain the responses of type IV units to notch-noise stimuli. Anatomical evidence supports this model configuration, and the results show that such a model can produce strong inhibition in type IV units for wide notches. The results thus suggest that WBIs, in narrow-input wide-output form, are sufficient to account for the notch sensitivity of DCN type IV units.     

Acoustic Basis of Directional Acuity in Laboratory Mice

The acoustic basis of auditory spatial acuity was investigated in CBA/129 mice by relating patterns of behavioral errors to directional features of the head-related transfer function (HRTF). Behavioral performance was assessed by training the mice to lick a water spout during sound presentations from a “safe” location and to suppress the response during presentations from “warning” locations. Minimum audible angles (MAAs) were determined by delivering the safe and warning sounds from different locations in the inter-aural horizontal and median vertical planes. HRTFs were measured at the same locations by implanting a miniature microphone and recording the gain of sound energy near the ear drum relative to free field. Mice produced an average MAA of 31° when sound sources were located in the horizontal plane. Acoustic measures indicated that binaural inter-aural level differences (ILDs) and monaural spectral features of the HRTF change systematically with horizontal location and therefore may have contributed to the accuracy of behavioral performance. Subsequent manipulations of the auditory stimuli and the directional properties of the ear produced errors that suggest the mice primarily relied on ILD cues when discriminating changes in azimuth. The MAA increased beyond 80° when the importance of ILD cues was minimized by testing in the median vertical plane. Although acoustic measures demonstrated a less robust effect of vertical location on spectral features of the HRTF, this poor performance provides further evidence for the insensitivity to spectral cues that was noted during behavioral testing in the horizontal plane.     

Histological and Physiological Investigation of Channelrhodopsin-2 and Halorhodopsin in the Dorsal Cochlear Nucleus

We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 (ChR2), or Halorhodopsin (HaloR) fused with mCherry (to form light gated cation channels or chloride pumps, respectively), into the dorsal cochlear nucleus (DCN). One to eighteen months later we examined the CN and inferior colliculus (IC) for evidence of virally transfected cells and processes. Production of ChR2 and HaloR was observed throughout the DCN. Rhodopsin localization within neurons was determined, with elongate, fusiform and giant cells identified based on morphology and location within the DCN. Production of ChR2 and HaloR was found at both the injection site as well as in regions projecting to and from the DCN. Light driven neuronal activity in the DCN was dependent upon the wavelength and intensity of the light, with only the appropriate wavelength resulting in activation and higher intensity light resulting in more neuronal activity. Transfecting cells via viral delivery of rhodopsins can be useful as a tract tracer and as a neuronal marker to delineate pathways. In the future rhodopsin delivery and activation may be developed as an alternative to electrical stimulation of neurons.     

Relearning Auditory Spectral Cues for Locations Inside and Outside the Visual Field

Previous research has demonstrated that, over a period of weeks, the auditory system accommodates to changes in the monaural spectral cues for sound locations within the frontal region of space. We were interested to determine if similar accommodation could occur for locations in the posterior regions of space, i.e. in the absence of contemporaneous visual information that indicates any mismatch between the perceived and actual location of a sound source. To distort the normal spectral cues to sound location, eight listeners wore small moulds in each ear. HRTF recordings confirmed that while the moulds substantially altered the monaural spectral cues, sufficient residual cues were retained to provide a basis for relearning. Compared to control measures, sound localization performance initially decreased significantly, with a sevenfold increase in front–back confusions and elevation errors more than doubled. Subjects wore the moulds continuously for a period of up to 60 days (median 38 days), over which time performance improved but remained significantly poorer than control levels. Sound localization performance for frontal locations (audio-visual field) was compared with that for posterior space (audio-only field), and there was no significant difference between regions in either the extent or rate of accommodation. This suggests a common mechanism for both regions of space that does not rely on contemporaneous visual information as a teacher signal for recalibration of the auditory system to modified spectral cues.     

Effects of excitant amino acids on acoustic responses of inferior colliculus neurons

Iontophoretic application of the excitant amino acids (EAAs), glutamate, aspartate and N-methyl-D-aspartate (NMDA) resulted in increased acoustically evoked and spontaneous firing of most neurons in the central nucleus of inferior colliculus (ICC). The excitatory effects of these EAAs were blocked by simultaneous application of EAA antagonists which selectively block the NMDA receptor subtype, 2-amino-5-phosphonovalerate or D-alpha-aminoadipate and to a lesser extent with non-selective EAA antagonists, such as glutamic acid diethylester. Application of NMDA receptor-selective EAA antagonists alone greatly reduced the firing of most ICC neurons examined, but non-selective EAA antagonists either increased or produced little change in firing of most ICC neurons examined. In this and previous studies cholinergic agonists were found to increase the firing of ICC neurons, but the cholinergic agonists were less effective in exciting ICC neurons than EAA agonists. Cholinergic antagonists in a previous study were considerably less effective in inhibiting the discharge of ICC neurons than were the EAA antagonists in the present study. These results, in conjunction with previous neurochemical and anatomical localization studies, support a possible role of an EAA as a candidate for afferent excitatory transmitter in neurons of the inferior colliculus.     

Sound pressure transformations by the head and pinnae of the adult Chinchilla (Chinchilla lanigera)

There are three main cues to sound location: the interaural differences in time (ITD) and level (ILD) as well as the monaural spectral shape cues. These cues are generated by the spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although the chinchilla has been used for decades to study the anatomy, physiology, and psychophysics of audition, including binaural and spatial hearing, little is actually known about the sound pressure transformations by the head and pinnae and the resulting sound localization cues available to them. Here, we measured the directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 9 adult chinchillas. The resulting localization cues were computed from the DTFs. In the frontal hemisphere, spectral notch cues were present for frequencies from ～6-18?kHz. In general, the frequency corresponding to the notch increased with increases in source elevation as well as in azimuth towards the ipsilateral ear. The ILDs demonstrated a strong correlation with source azimuth and frequency. The maximum ILDs were <10?dB for frequencies <5?kHz, and ranged from 10-30?dB for the frequencies >5?kHz. The maximum ITDs were dependent on frequency, yielding 236?μs at 4?kHz and 336?μs at 250?Hz. Removal of the pinnae eliminated the spectral notch cues, reduced the acoustic gain and the ILDs, altered the acoustic axis, and reduced the ITDs.     

Binaural evoked brain stem potentials. Effect of sound direction on inferior colliculus response]

Auditory evoked brain-stem responses were recorded using binaural stimulation on 12 test subjects. Rotation of the sound source in the horizontal plane was simulated digitally using a binaural mixing console. Binaural processing in the inferior colliculus was thus demonstrated in humans. The amplitude of the inferior colliculus response depends in an almost linear manner on sound direction and presents a typical directionality. While the amplitude is considered an important central code of sound direction, response latency of the inferior colliculus is controversial. The results confirm neuronal mechanisms which had been established by animal experiments for single units of the inferior colliculus and the auditory cortex.     

Rate Representation of Tones in Noise in the Inferior Colliculus of Decerebrate Cats

Neurons in the central nucleus of the inferior colliculus (ICC) of decerebrate cats show three major response patterns when tones of different frequencies and sound-pressure levels (SPLs) are presented to the contralateral ear. The frequency response maps of type I units are uniquely defined by a narrow excitatory area at best frequency (BF: a unit's most sensitive frequency) and surrounding inhibition at higher and lower frequencies. As a result of this receptive field organization, type I units exhibit strong excitatory responses to BF tones but respond only weakly to broadband noise (BBN). These response characteristics predict that type I units are well suited to encode narrowband signals in the presence of background noise. To test this hypothesis, the dynamic range properties of ICC unit types were measured under quiet conditions and in multiple levels of continuous noise. As observed in previous studies of the auditory nerve and cochlear nucleus, type I units showed upward threshold shifts and discharge rate compression in background noise that partially degraded the dynamic range properties of neural representations at high noise levels. Although the other two unit types in the ICC showed similar trends in threshold shift and noise compression, their ability to encode auditory signals was compromised more severely in increasing noise levels. When binaural masking effects were simulated, only type I units showed an enhanced representation of spatially separated signals and maskers that was consistent with human perceptual performance in independent psychoacoustic observations. These results support the interpretation that type I units play an important role in the auditory processing of narrowband signals in background noise and suggest a physiological basis for spatial factors that govern signal detection under free-field listening conditions.     

Responses to Combinations of Tones in the Nuclei of the Lateral Lemniscus

Combination-sensitive neurons integrate specific spectral and temporal elements in biologically important sounds, and they may underlie the analysis of biosonar and social vocalizations. Combination-sensitive neurons are found in the forebrain of a variety of vertebrates. In the mustached bat, they also occur in the central nucleus of the inferior colliculus (ICC). However, it is not known where combination-sensitive response properties emerge. To address this question, we used a two-tone paradigm to examine responses of single units to combination stimuli in a brainstem structure, the nuclei of the lateral lemniscus (NLL). We recorded and histologically localized 101 single units in the NLL. The majority (82%) of units had a single excitatory frequency tuning curve. Seven units had two separate excitatory frequency tuning curves but displayed no combinatorial interaction. Twelve units were combination-sensitive. Of these, three units were facilitated by the combination of two separate frequency bands and nine units were inhibited by combinatorial stimuli. The three facilitatory neurons had excitatory responses tuned to the second harmonic constant frequency (CF2, 57-60 kHz) component of the biosonar signal and were facilitated by a second signal within the first harmonic (Hl, 24-30 kHz) of the biosonar call. Most of the inhibitory interactions occurred between signals in the frequency bands associated with the frequency-modulated (FM) components of the biosonar call. The strongest combinatorial effects (facilitatory and inhibitory) were elicited by simultaneous onset of the two signals (i.e., 0 ms delay). All combination-sensitive units were in the intermediate nucleus of the NLL (INLL), which in bats is a hypertrophied structure that projects strongly to combination-sensitive neurons in the ICC. Thus, the combination-sensitive neurons in the INLL may impart their response properties onto ICC neurons. However, the small number of facilitatory combination-sensitive neurons in the NLL suggests that the majority of these combinatorial responses originate in the ICC.     

Differential Effect of Near-Threshold Stimulus Intensities on Sound Localization Performance in Azimuth and Elevation in Normal Human Subjects

The ability of humans to localize sounds remains relatively constant across a range of intensities well above detection threshold, and increasing the spectral content of the stimulus results in an improvement in localization ability. For broadband stimuli, intensities near detection threshold result in fewer and weaker binaural cues used in azimuth localization because the stimulus energy at the high- and low-frequency ends of the audible spectrum fall below detection threshold. Thus, the ability to localize broadband sounds in azimuth is predicted to be degraded at audible but near threshold stimulus intensities. The spectral cues for elevation localization (spectral peaks and notches generated by the head-related transfer function) span a narrower frequency range than those for azimuth. As the stimulus intensity decreases, the ability to detect the stimulus frequencies corresponding to the spectral notches will be more strongly affected than the ability to detect frequencies outside the range where these spectral cues are useful. Consequently, decreasing the stimulus intensity should degrade localization in both azimuth and elevation and create a greater deficit in elevation localization due to the narrower band of audible frequencies containing elevation cues compared to azimuth cues. The present study measured the ability of 11 normal human subjects to localize broadband noise stimuli along the midsagittal plane and horizontal meridian at stimulus intensities of 14, 22, and 30 dB above the subject's detection threshold using a go/no-go behavioral paradigm. Localization ability decreased in both azimuth and elevation with decreasing stimulus intensity, and this effect was greater on localization in elevation than on localization in azimuth. The differential effects of stimulus intensity on sound localization in azimuth and elevation found in the present study may provide a valuable tool in investigating the neural correlates of sound location perception.     

耳蜗急性纯音损伤后下丘及耳蜗核快速功能重组

实验比较高强度纯音损伤耳蜗局部区域前后，耳蜗背核及下丘接近损伤区边缘的神经元反应特性的改变。致损纯音的频率高于神经元的特征频率，且位于其兴奋区以外，所以不影响其兴奋性输入。结果发现此种纯音损伤在逾半数的神经元产生不同程度的去抑制效应，提示皮层的功能重组可能部分地起源于低位中枢的功能改变，下丘和耳蜗背核的抑制性神经网络具有相当程度的侧抑制组分。     

Monaural and binaural processing in the ventral nucleus of the lateral lemniscus: a major source of inhibition to the inferior colliculus

The ventral nucleus of the lateral lemniscus (VNLL) is a major source of input to the inferior colliculus. This paper reviews recent studies of neural responses in the VNLL of the unanesthetized rabbit. The VNLL has generally been viewed as a monaural nucleus, with its neurons responding primarily to stimulation of the contralateral ear. In the rabbit, the VNLL is divided into a medial division (VNLLm) comprising neurons intercalated in the medial limb of the lemniscus, a compact lateral division (VNLLl), and a dorsal division. The VNLLm contains an abundance of neurons sensitive to interaural temporal disparities (ITDs), one of the major binaural cues for sound localization. These neurons respond only at the onset of tones, and therefore appear to encode the ITDs of transients. Even in the VNLLl, many neurons are sensitive to binaural stimulation. The VNLLl contains a variety of neurons with different discharge patterns, the two most common of which are sustained and onset. The discharge patterns, frequency-tuning and dynamic ranges of VNLLl neurons indicate that this division is able to supply the inferior colliculus with a variety of inputs, each serving a different function in the analysis of sound.     

耳蜗急性纯音损伤后下丘及耳蜗核快速功能重组

实验比较高强度纯音损伤耳蜗局部区域前后，耳蜗背核及下丘接近损伤区边缘的神经元反应特性的改变。致损纯音的频率高于神经元的特征频率，且位于其兴奋区以外，所以不影响其兴奋性输入，结果发现此种纯音损伤在逾半数的神经元产生不同程度的去抑制效应，提示皮歧的功能重组可能部分地起源于低位中枢的功能改变，下丘和耳蜗背核的抑制性神经网络具有相当程度的侧抑制组分。     

The Structural Development of the Mouse Dorsal Cochlear Nucleus

The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) that is thought to be involved in sound localization in the vertical plane and in feature extraction of sound stimuli. The main principal cell type (pyramidal cells) integrates auditory and non-auditory inputs, which are considered to be important in performing sound localization tasks. This study aimed to investigate the histological development of the CD-1 mouse DCN, focussing on the postnatal period spanning the onset of hearing (P12). Fluorescent Nissl staining revealed that the three layers of the DCN were identifiable as early as P6 with subsequent expansion of all layers with age. Significant increases in the size of pyramidal and cartwheel cells were observed between birth and P12. Immunohistochemistry showed substantial changes in synaptic distribution during the first two postnatal weeks with subsequent maturation of the presumed mossy fibre terminals. In addition, GFAP immunolabelling identified several glial cell types in the DCN including the observation of putative tanycytes for the first time. Each glial cell type had specific spatial and temporal patterns of maturation with apparent rapid development during the first two postnatal weeks but little change thereafter. The rapid maturation of the structural organization and DCN components prior to the onset of hearing possibly reflects an influence from spontaneous activity originating in the cochlea/auditory nerve. Further refinement of these connections and development of the non-auditory connections may result from the arrival of acoustic input and experience dependent mechanisms.     

Functional specialization in non-primary auditory cortex of the cat: areal and laminar contributions to sound localization

The purpose of this study is to: (1) examine the relative contributions of the 13 acoustically-responsive regions of the cerebral cortex to sound localization; (2) examine the laminar contributions to spatial localization behavior for each of the cortical areas identified to be critical for accurately determining the position of a sound source; and (3) synthesize the findings from sound localization studies and the underlying corticocortical and corticotectal connections to develop a processing system for sound localization information within and between the cerebral cortex and the superior colliculus. First, we examined performance on a sound localization task before, during, and after unilateral or bilateral reversible cooling deactivation of each region of acoustically-responsive cortex. Overall, unilateral deactivation of primary auditory cortex and the dorsal zone (AI/DZ), the posterior auditory field (PAF), or the auditory field of the anterior ectosylvian sulcus (AES) yielded profound sound localization deficits in the contralateral field. Bilateral deactivations of the same regions yielded bilateral sound localization deficits. Second, graded cooling of AI/DZ or PAF showed that deactivation of only the superficial layers was required to elicit sound localization deficits. However, graded cooling of AES revealed that cooling of the superficial layers alone does not cause significant sound localization deficits. Profound deficits were identified only when cooling extended through the full thickness of AES cortex. Therefore, we propose that the superficial layers of AI/DZ or PAF and the deeper layers of AES are necessary for determining the precise location of a sound source. Finally, when these results are combined with data on corticocortical and corticotectal projections, we propose that signals processed in the superficial layers of AI, DZ, or PAF feed forward to the auditory field of AES. In turn, neurons in the deeper layers of AES project to the intermediate and deeper layers of the superior colliculus. Therefore, we propose that sound localization signals processed in primary and non-primary auditory cortex are transmitted to the superior colliculus by means of the auditory field of the AES.