Frequency selectivity in monkey auditory nerve studied with suprathreshold multicomponent stimuli.

Data from non-human primates can help extend observations from non-primate species to humans. Here we report measurements on the auditory nerve of macaque monkeys in the context of a controversial topic important to human hearing. A range of techniques have been used to examine the claim, which is not generally accepted, that human frequency tuning is sharper than traditionally thought, and sharper than in commonly used animal models. Data from single auditory-nerve fibers occupy a pivotal position to examine this claim, but are not available for humans. A previous study reported sharper tuning in auditory-nerve fibers of macaque relative to the cat. A limitation of these and other single-fiber data is that frequency selectivity was measured with tonal threshold-tuning curves, which do not directly assess spectral filtering and whose shape is sharpened by cochlear nonlinearity. Our aim was to measure spectral filtering with wideband suprathreshold stimuli in the macaque auditory nerve. We obtained responses of single nerve fibers of anesthetized macaque monkeys and cats to a suprathreshold, wideband, multicomponent stimulus designed to allow characterization of spectral filtering at any cochlear locus. Quantitatively the differences between the two species are smaller than in previous studies, but consistent with these studies the filters obtained show a trend of sharper tuning in macaque, relative to the cat, for fibers in the basal half of the cochlea. We also examined differences in group delay measured on the phase data near the characteristic frequency versus in the low-frequency tail. The phase data are consistent with the interpretation of sharper frequency tuning in monkey in the basal half of the cochlea. We conclude that use of suprathreshold, wide-band stimuli supports the interpretation of sharper frequency selectivity in macaque nerve fibers relative to the cat, although the difference is less marked than apparent from the assessment with tonal threshold-based data.

The volley theory and the spherical cell puzzle.

Temporal coding in the auditory nerve is strikingly transformed in the cochlear nucleus. In contrast to fibers in the auditory nerve, some neurons in the cochlear nucleus can show "picket fence" phase-locking to low-frequency pure tones: they fire a precisely timed action potential at every cycle of the stimulus. Such synchronization enhancement and entrainment is particularly prominent in neurons with the spherical and globular morphology, described by Osen [Osen KK (1969) Cytoarchitecture of the cochlear nuclei in the cat. J Comp Neurol 136:453-483]. These neurons receive large axosomatic terminals from the auditory nerve--the end bulbs and modified end bulbs of Held--and project to binaural comparator nuclei in the superior olivary complex. The most popular model to account for picket fence phase-locking is monaural coincidence detection. This mechanism is plausible for globular neurons, which receive a large number of inputs. We draw attention to the existence of enhanced phase-locking and entrainment in spherical neurons, which receive too few end-bulb inputs from the auditory nerve to make a coincidence detection of end-bulb firings a plausible mechanism of synchronization enhancement.

Interaural time sensitivity in the inferior colliculus of the albino cat.

Anatomical studies of the Creel albino cat have demonstrated a pronounced atrophy of cells in the medial superior olive, a structure thought to be important for the detection of interaural time differences (ITDs). We looked for physiological abnormalities in the binaural interaction of cells in three albino cats by recording from single cells in the central nucleus of the inferior colliculus to ITDs of tones and noise. We found that the sensitivity to ITDs of tones and noise was somewhat diminished in the albino cats as compared to normally pigmented cats, though this deficit was only evident when a population of cells was examined. The range of sensitivity of individual cells for both tones and noise was the same in albinos and pigmented animals. Our anatomical measurements showed a smaller reduction in cross-sectional area of cells in the medial superior olive than that reported earlier, and the cell bodies in the medial superior olive of the albinos were less elongated than in normal cats.

Projections of physiologically characterized spherical bushy cell axons from the cochlear nucleus of the cat: evidence for delay lines to the medial superior olive.

Bushy cells in the anteroventral cochlear nucleus (AVCN) receive their principal excitatory input from the auditory nerve and are the primary source of excitatory input to more centrally located brainstem auditory nuclei. Despite this pivotal position in the auditory pathway, details of the basic physiological information being carried by axons of these cells and their projections to more central auditory nuclei have not been fully explored. In an attempt to clarify these details, we have physiologically characterized and anatomically labeled individual axons of the spherical bushy cell (SBC) class of the cat AVCN. The characteristic frequencies (CFs) of our injected SBC population are low, all less than 12 kHz and primarily (83%) less than 3 kHz, while their spontaneous activity is comparatively high (mean of 59 spikes/sec). In response to short tone bursts at CF, low CF (< 1 kHz) SBC units can phase-lock better than auditory nerve fibers. SBCs with CFs above 1 kHz have primary-like responses at all stimulus levels and can show robust phase-locking to an off-CF, 500 Hz tone. When compared with our previously reported population of labeled globular bushy cells (GBC; Smith et al., 1991, J. Comp. Neurol. 304:387-407), some similarities and differences are apparent in both physiological response properties and axonal projection pattern. GBCs show no low frequency bias in CFs, have lower spontaneous rates, and the high CF units exhibit a primary-like-with-notch response at high stimulus levels as a consequence of a very well timed onset component. Low CF, GBC short tone responses are indistinguishable from those of SBCs. Anatomically, the axons of SBCs cross the midline in the dorsal component of the trapezoid body and typically innervate the medial superior olive (MSO) on both sides, the ipsilateral lateral superior olive (LSO), and the contralateral ventral nucleus of the lateral lemniscus (VNLL). The projections to the contralateral, but not the ipsilateral MSO, show a rostral to caudal delay line configuration, similar to the scheme first proposed by Jeffress (1948, J. Comp. Psychol. 41:35-39). The form of this delay line is consistent with the topographic map of interaural time delays reported by Yin and Chan (1990, J. Neurophysiol. 64:465-488). Projections to the ipsilateral LSO often take an indirect route. In contrast, GBC axons travel in the ventral component of the trapezoid body, never innervate the MSO, rarely innervate the ipsilateral LSO, and always innervate the contralateral medial nucleus of the trapezoid body. The terminal specializations of both SBC and GBC axons contain round vesicles.

Projections of physiologically characterized globular bushy cell axons from the cochlear nucleus of the cat.

We made intraaxonal recordings from 30 individual globular bushy cell axons in the trapezoid body of the cat using HRP-filled glass microelectrodes. With subsequent HRP injection, we determined their axonal projection patterns. For cells with characteristic frequencies (CFs) above 3 kHz, short-tone peristimulus time histograms (PSTHs) at CF were typically primarylike at low tone intensities and primarylike with notch (PLN) or onset with low sustained activity (OL) at higher stimulus levels. Cells with CFs between 1 and 3 kHz showed the same response features with the spikes in the sustained region of the response phase-locked to the stimulus tone. Cells with CFs below 1 kHz showed phase-locked PSTHs with exceptionally high levels of synchrony compared to eighth nerve fibers with comparable CFs. This exceptional phase-locking was also noted when cells with CFs of 1-3 kHz were presented with tones below 1 kHz. Although the globular bushy cell axons were not completely filled from the soma of origin to terminal fields in the contralateral brainstem, a number of consistent anatomical features were distinguished in the population. All but one of the myelinated axons crossed the midline in the middle, large fiber component of the trapezoid body. Ipsilaterally, the axon always gave off from one to four collateral branches whose major targets were the posterior periolivary nucleus (PPO) and the lateral nucleus of the trapezoid body (LNTB). Minor termination sites for ipsilateral collateral branches were the dorsolateral periolivary nucleus (DLPO) and the lateral superior olive (LSO). Contralaterally the axon gave rise to one or two calyces of Held in the medial nucleus of the trapezoid body (MNTB). Three other major collateral branches arose from the contralateral axon and innervated a consistent set of areas. One headed caudally to innervate an area just ventromedial to the facial nucleus. Another followed the sixth nerve dorsally to innervate the dorsomedial periolivary nucleus (DMPO). A third collateral headed rostrally toward the ventral nucleus of the lateral lemniscus (VNLL), giving off occasional small sidebranches. Although each injected axon gave rise to a collateral that innervated the MNTB, it did not necessarily give rise to all three of the other collateral branches.

Direction selectivity in human visual perception, investigated with low contrast gratings.

Velocity thresholds (VT's) of direction selective mechanism were measured with coarse low contrast gratings, visible only when moving. direction of movement was detected only in a movement perception domain (MPD), limited by upper and lower VT's and a minimum exposure time of movement. MPD expanded with increasing contrast or increasing stimulus area. MPD shifted towards higher velocities with lower spatial frequencies or with larger stimulus eccentricities. Form perception in MPD was best at optimal velocities; the spatial structure of the gratings was not evident at the VT level. These observations suggest a velocity tuned sensitivity of direction selective mechanisms and an association of movement and form perception with the activity of movement analysing neurons.

Envelope coding in the lateral superior olive. II. Characteristic delays and comparison with responses in the medial superior olive.

1. Spike rates of cells in the cat's lateral superior olive (LSO) depend on interaural level differences (ILDs) and envelope interaural time differences (ITDs) of amplitude-modulated tones presented to both ears. We previously proposed that these sensitivities arise from a common mechanism, which is the IE binaural interaction (Inhibited by the contralateral and Excited by the ipsilateral ear). As a further test of that proposal and to gain a better understanding of the importance of this ITD-sensitivity, responses to monaural and binaural modulation are compared here over a range of modulation frequencies. 2. At low modulation frequencies, LSO-IE cells respond maximally when the envelopes of the amplitude-modulated stimuli at the two ears are out-of-phase by a half-cycle. This phase difference changes in a systematic way, which varies from cell to cell, when modulation frequency is increased. Mean interaural phase, measured over a range of modulation frequencies, was subjected to a characteristic delay analysis. Two measures were extracted: characteristic delay, which reflects differences in conduction delay between ipsi- and contralateral pathways, and characteristic phase, which reflects their sign of interaction. Most characteristic delays were within the physiological range of ITDs. There was a small bias toward positive delays, indicating a longer conduction time for the contralateral pathway. Characteristic phases were tightly distributed approximately 0.5 cycles, consistent with the proposed IE mechanism for ITD-sensitivity. 3. Increases in the modulation frequency of binaural stimuli beyond approximately 300 Hz consistently caused a profound decrease in average spike rate, as well as a decrease in the modulation of spike rate by ITD. The upper limit of ITD-sensitivity was 800 Hz. Sensitivity to envelope ITDs therefore is limited to a much lower range of frequencies than sensitivity to ITDs in fine-structure, e.g., as found in the medial superior olive (MSO), which operates up to several kilo Hertz. 4. A small sample of high-frequency EE cells (excited by both ears) in MSO also was tested with binaural amplitude-modulated stimuli. MSO-EE cells showed weak envelope ITD-sensitivity over a limited range of modulation frequencies. Consistent with the EE interaction, characteristic phases clustered approximately 0 cycles. 5. Mean interaural phase was compared with the phase of responses to monaural modulation. The difference between the ipsilateral and contralateral phases correlated well with the phase measured binaurally, both for LSO and MSO cells. 6. Many features of LSO-IE responses were mimicked by the simplest possible computer model, consisting of subtraction and rectification of low-pass filtered envelope waveforms. Differences between model and physiological results are suggestive of a temporal limitation in the binaural interaction that creates the ITD-sensitivity. 7. These results provide additional evidence for LSO ITD-sensitivity paralleling human psychophysical results. The stimulus boundaries within which ITD-sensitivity occurs suggest that it has a limited role in free-field conditions. It is traditionally thought that, to contribute to the perceived change in spatial location of a sound source, the LSO needs to show a change in overall firing rate summed across cells. This is achieved with small ILDs, but requires large ITDs, because the latter cue is less potent in single cells and has varied effects across cells by virtue of differences in characteristic delay.

Response classes in the dorsal cochlear nucleus and its output tract in the chloralose-anesthetized cat.

Neurons in the dorsal cochlear nucleus (DCN) can be classified into three major physiological classes on the basis of responses to pure tone and broadband noise stimuli. A circuit diagram that associates these classes with different cell types has been proposed. According to this proposal, type II cells are inhibitory interneurons that respond well to tones and poorly to broadband noise, type IV cells are projection neurons with the opposite behavior, and type III cells are an inhomogeneous class with intermediate properties. To test the associations proposed, I compared the response type distribution in the DCN with its output tract, the dorsal acoustic stria (DAS), in chloralose-anesthetized cats. Axonal recordings in the DAS showed type III and IV responses as in DCN, but no type II responses. Compared with reports in decerebrate animals, fewer type IV neurons were encountered having sustained inhibition that generated strongly nonmonotonic responses to tones in both DCN and DAS. The presence of type II responses in the nucleus, but not in the output tract, offers strong support for the proposed association with DCN interneurons. On the other hand, the distinction between type III and IV responses needs refinement because the differences are only graded and because both types of responses occur in DAS, which shows that they are both associated with projection neurons.

Responses to amplitude-modulated tones in the auditory nerve of the cat.

Sinusoidally amplitude-modulated (AM) tones are frequently used in psychophysical and physiological studies, yet a comprehensive study on the coding of AM tones in the auditory nerve is lacking. AM responses of single auditory-nerve fibers of the cat are studied, systematically varying modulation depth, frequency, and sound level. Synchrony-level functions were nonmonotonic with maximum values that were inversely correlated with spontaneous rate (SR). In most fibers, envelope phase-locking showed a positive gain. Modulation transfer functions were uniformly low pass. Their corner frequency increased with characteristic frequency (CF), but changed little for CFs above 10 kHz. The highest modulation frequencies to which phase locking occurred were more than 0.8 oct lower than the highest frequencies to which phase locking to pure tones occurs. Cumulative, or unwrapped, phase increased linearly with modulation frequency: The slope was inversely related to CF, and slightly higher than group delays reported for pure tones. High SR, low CF fibers showed the poorest envelope phase locking. In some low CF fibers, phase locking increased at high levels, associated with "peak-splitting" phenomena. Changes in average rate due to modulation were small, and could be enhancement or suppression.

Envelope coding in the lateral superior olive. I. Sensitivity to interaural time differences.

1. Interaural level differences (ILDs), created by the head and pinna, have long been known to be the dominant acoustic cue for azimuthal localization of high-frequency tones. However, psychophysical experiments have demonstrated that human subjects can also lateralize complex high-frequency sounds on the basis of interaural time differences (ITDs) of the signal envelope. The lateral superior olive (LSO) is one of two pairs of binaural nuclei where the primary extraction of binaural cues for sound source location occurs. "IE" cells in LSO are inhibited by stimuli to the contralateral and excited by stimuli to the ipsilateral ear, and their response rate is therefore dependent on ILD. Anatomic specializations in the afferent pathways to the LSO suggest that this circuit also has a function in the detection of timing cues. We hypothesized that, besides ILD sensitivity, the IE property also conveys a sensitivity to ITDs of amplitude-modulated (AM) tones and could provide the physiological substrate for the psychophysical effect mentioned above. 2. In extracellular recordings from binaural LSO cells in barbiturate-anesthetized cats, response rate was a periodic function of ITDs of AM stimuli, i.e., all cells displayed ITD sensitivity. Binaural responses were smaller than responses to stimulation of the ipsilateral ear alone and were minimal when the envelopes in both ears were in-phase or nearly so. There was good correspondence between responses to ITDs and to dynamic interaural phase differences (IPDs), created by a difference in the envelope frequency to the two ears. Qualitatively, the responses were consistent with the outcome of an IE operation on temporally structured inputs. 3. To compare the relative importance of ILD and ITD, responses to combinations of the two cues were obtained. Despite robust ITD sensitivity in all binaural LSO cells encountered, the changes in response rate that would occur in response to naturally occurring ITDs were small in comparison with the changes expected for naturally occurring ILDs. The main limitation on ITD sensitivity was a steep decline in average discharge rate as the modulation frequency exceeded several hundred Hertz. 4. ITD sensitivity was also present to broadband stimuli, again with minimal rates occurring near 0 ITD. The sensitivity depended in a predictable fashion on the passband of filtered noise and was absent to binaurally uncorrelated noise bands. In response to clicks, ILDs interacted with ITD in a complicated fashion involving amplitude and latency effects. 5. Three low-characteristic frequency (CF) LSO cells were encountered that were IE and showed ITD sensitivity to the fine structure of low-frequency stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanical and "temporal" filtering as codeterminants of the response by cat primary fibers to amplitude-modulated signals.

From previous studies it appears that at least two factors limit the upper frequency at which auditory-nerve (AN) fibers can entrain to the envelope of a sinusoidally amplitude-modulated (AM) tone. Cochlear mechanical filtering insures that, in the local motion driving a fiber tuned to the carrier, sidetone amplitudes decrease as sidetone displacement envelopes separate with modulation frequency (fm). Only if at least one side-tone's amplitude is large enough, relative to carrier's, will there be modulation of basilar motion at the point tuned to the carrier. In addition, processes within haircell and fiber limit the upper frequency at which they follow variations in amplitude. To assess change, along the cochlea, in the two factors' relative importance. AN modulation transfer functions (MTFs) [Joris and Yin, J. Acoust. Soc. Am. 91, 215-232 (1992)] were replotted versus distance in mm between sidetones and carrier, using an empirical frequency-place function [Greenwood, J. Acoust. Soc. Am. 87, 2592-2605 (990)]. MTF bandwidths, converted to mm changed little over the apical 40% of cochlea but decreased basally. Expressed in Hz, they increased from apex to base and reached an upper limit at a characteristic frequency (CF) of 20 kHz. This is consistent with the idea that at high CFs phase-locking constraints limit envelope-following before mechanical filtering does, while in apical regions spatial filtering reduces envelope amplitude variation, hence envelope following, before limits on phase locking do. Consistently, MTF bandwidths parallel tuning curve bandwidths in the apical cochlea, but are smaller near the base, where tuning curve bandwidths and spatial filtering appear constant.

Envelope coding in the lateral superior olive. III. Comparison with afferent pathways.

Binaural cues for spatial localization of complex high-frequency sounds are interaural level and time differences (ILDs and ITDs). We previously showed that cells in the lateral superior olive (LSO) are sensitive to ITDs in the envelope of sinusoidally amplitude-modulated (AM) signals up to a modulation frequency of only approximately 800 Hz. To understand the limitations in this ITD-sensitivity, we here compare responses to monaural modulation in LSO and its input pathways, derived from cochlear nucleus and medial nucleus of the trapezoid body. These pathways have marked functional and morphological specializations, suggestive of adaptations for timing. Afferent cell populations were identified on the basis of electrophysiological signatures, and for each population, average firing rate and synchronization to AM tones were compared with auditory-nerve fibers and LSO cells. Except for an increase in modulation gain in some subpopulations, synchronization of LSO afferents was very similar to that in auditory nerve fibers in its dependency on sound pressure level (SPL), modulation depth, and modulation frequency. Distributions of cutoff frequencies of modulation transfer functions were largely coextensive with the distribution in auditory nerve. Group delays, measured from the phase of the response modulation as a function of modulation frequency, showed an orderly dependence on characteristic frequency and cell type and little dependence on SPL. Similar responses were obtained to a modulated broadband carrier. Compared with their afferents, LSO cells synchronized to monaurally modulated stimuli with a higher gain but often over a narrower range of modulation frequencies. Considering the scatter in afferent and LSO cell populations, ipsi- and contralateral responses were well matched in cutoff frequency and magnitude of delays. In contrast to their afferents, LSO cells show a decrease in average firing rate at high modulation frequencies. We conclude that the restricted modulation frequency range over which LSO cells show ITD-sensitivity does not result from loss of envelope information along the afferent pathway but is due to convergence or postsynaptic effects at the level of the LSO. The faithful transmission of envelope phase-locking in LSO afferents is consistent with their physiological and morphological adaptations, but these adaptations are not commensurate with the rather small effects of physiological ITDs reported previously, especially when compared with effects of ILDs. We suggest that these adaptations have evolved to allow a comparison of instantaneous amplitude fluctuations at the two ears rather than to extract interaural timing information per se.

Temporal and binaural properties in dorsal cochlear nucleus and its output tract.

The dorsal cochlear nucleus (DCN) is one of three nuclei at the terminal zone of the auditory nerve. Axons of its projection neurons course via the dorsal acoustic stria (DAS) to the inferior colliculus (IC), where their signals are integrated with inputs from various other sources. The DCN presumably conveys sensitivity to spectral features, and it has been hypothesized that it plays a role in sound localization based on pinna cues. To account for its remarkable spectral properties, a DCN circuit scheme was developed in which three inputs converge onto projection neurons: auditory nerve fibers, inhibitory interneurons, and wide-band inhibitors, which possibly consist of Onset-chopper (Oc) cells. We studied temporal and binaural properties in DCN and DAS and examined whether the temporal properties are consistent with the model circuit. Interneurons (type II) and projection (types III and IV) neurons differed from Oc cells by their longer latencies and temporally nonlinear responses to amplitude-modulated tones. They also showed evidence of early inhibition to clicks. All projection neurons examined were inhibited by stimulation of the contralateral ear, particularly by broadband noise, and this inhibition also had short latency. Because Oc cells had short-latency responses and were well driven by broadband stimuli, we propose that they provide short-latency inhibition to DCN for both ipsilateral and contralateral stimuli. These results indicate more complex temporal behavior in DCN than has previously been emphasized, but they are consistent with the recently described nonlinear behavior to spectral manipulations and with the connectivity scheme deduced from such manipulations.

Neural processing of amplitude-modulated sounds.

Amplitude modulation (AM) is a temporal feature of most natural acoustic signals. A long psychophysical tradition has shown that AM is important in a variety of perceptual tasks, over a range of time scales. Technical possibilities in stimulus synthesis have reinvigorated this field and brought the modulation dimension back into focus. We address the question whether specialized neural mechanisms exist to extract AM information, and thus whether consideration of the modulation domain is essential in understanding the neural architecture of the auditory system. The available evidence suggests that this is the case. Peripheral neural structures not only transmit envelope information in the form of neural activity synchronized to the modulation waveform but are often tuned so that they only respond over a limited range of modulation frequencies. Ascending the auditory neuraxis, AM tuning persists but increasingly takes the form of tuning in average firing rate, rather than synchronization, to modulation frequency. There is a decrease in the highest modulation frequencies that influence the neural response, either in average rate or synchronization, as one records at higher and higher levels along the neuraxis. In parallel, there is an increasing tolerance of modulation tuning for other stimulus parameters such as sound pressure level, modulation depth, and type of carrier. At several anatomical levels, consideration of modulation response properties assists the prediction of neural responses to complex natural stimuli. Finally, some evidence exists for a topographic ordering of neurons according to modulation tuning. The picture that emerges is that temporal modulations are a critical stimulus attribute that assists us in the detection, discrimination, identification, parsing, and localization of acoustic sources and that this wide-ranging role is reflected in dedicated physiological properties at different anatomical levels.

Enhancement of neural synchronization in the anteroventral cochlear nucleus. II. Responses in the tuning curve tail.

1. Discharges of neurons in the peripheral auditory system contain information about the temporal features of acoustic stimuli. Phase-locking of neurons in the anteroventral cochlear nucleus (AVCN) is usually reported to be less robust than in auditory nerve (AN) fibers, which provide their major input. In a companion paper we reported that some cells in AVCN of the cat show enhanced phase-locking compared with the AN when stimulated at the frequency to which they are most sensitive [characteristic frequency (CF)]. We called neurons "high-sync" when they showed vector strengths (R, a measure of phase-locking) > or = 0.9. Here we report phase-locking properties to stimuli at frequencies below CF. 2. Horseradish peroxidase-filled glass micropipettes or metal microelectrodes were inserted into the trapezoid body (TB), which is the large output tract of the AVCN. Acoustically driven fibers were classified on the basis of the shape of the poststimulus time (PST) histograms to short tone bursts at CF. We then presented low-frequency tones of increasing SPL and determined the maximum R value at 500 Hz (R500) for each fiber. Using the same experimental protocol we studied phase-locking in the ANs of two animals because maximal R values at the tuning curve tail have not been reported for AN fibers. 3. Although phase-locking in AN fibers is usually assumed to be independent of CF, we found that fibers with CF > 2 kHz tended to have higher R500 values than fibers with CF < or = 2 kHz. Moreover, R500 was > or = 0.9 in 20% (42 of 196) of the fibers studied and could be as high as 0.95. This population of fibers was defined as having "high-sync tails" and consisted almost entirely of fibers with low or medium spontaneous rate. 4. High-CF TB fibers stimulated at 500 Hz showed very high phase-locking. High-sync tails (R500 > or = 0.9) were found in 41 of 70 TB fibers. For a subset of these fibers (1/3 in total: 23 of 70) phase-locking was higher than is ever observed in the AN (R500 > or = 0.95); these fibers were defined as showing synchronization "enhancement." Virtually all fibers showing synchronization enhancement had primary-like-with-notch (PLN) PST histograms. Chopper and primary-like fibers showed high-sync tails for CFs > 3 kHz. 5. Synchronization filter functions were obtained for high-CF AN fibers by determining maximum synchronization for a range of stimuli below CF.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomy and physiology of principal cells of the medial nucleus of the trapezoid body (MNTB) of the cat.

We have recorded from principal cells of the medial nucleus of the trapezoid body (MNTB) in the cat's superior olivary complex using either glass micropipettes filled with Neurobiotin or horseradish peroxidase for intracellular recording and subsequent labeling or extracellular metal microelectrodes relying on prepotentials and electrode location. Labeled principal cells had cell bodies that usually gave rise to one or two primary dendrites, which branched profusely in the vicinity of the cell. At the electron microscopic (EM) level, there was a dense synaptic terminal distribution on the cell body and proximal dendrites. Up to half the measured cell surface could be covered with excitatory terminals, whereas inhibitory terminals consistently covered about one-fifth. The distal dendrites were very sparsely innervated. The thick myelinated axon originated from the cell body and innervated nuclei exclusively in the ipsilateral auditory brain stem. These include the lateral superior olive (LSO), ventral nucleus of the lateral lemniscus, medial superior olive, dorsomedial and ventromedial periolivary nuclei, and the MNTB itself. At the EM level the myelinated collaterals gave rise to terminals that contained nonround vesicles and, in the LSO, were seen terminating on cell bodies and primary dendrites. Responses of MNTB cells were similar to their primary excitatory input, the globular bushy cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with low characteristic frequencies (CFs) was low, whereas it tended to be higher for higher CF units. In response to short tones, a low frequency MNTB cell showed enhanced phase-locking abilities, relative to auditory nerve fibers. For cells with CFs >1 kHz, the short tone response often resembled the primary-like with notch response seen in many globular bushy cells, with a well-timed onset component. Exceptions to and variations of this standard response were also noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell response was delayed slightly, as would be expected given the synapse interposed between the two cell types. Our data thus confirm that, in the cat, the MNTB receives and converts synaptic inputs from globular bushy cells into a reasonably accurate reproduction of the bushy cell spike response. This MNTB cell output then becomes an important inhibitory input to a number of ipsilateral auditory brain stem nuclei.

Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus.

The anatomical and biophysical specializations of octopus cells allow them to detect the coincident firing of groups of auditory nerve fibers and to convey the precise timing of that coincidence to their targets. Octopus cells occupy a sharply defined region of the most caudal and dorsal part of the mammalian ventral cochlear nucleus. The dendrites of octopus cells cross the bundle of auditory nerve fibers just proximal to where the fibers leave the ventral and enter the dorsal cochlear nucleus, each octopus cell spanning about one-third of the tonotopic array. Octopus cells are excited by auditory nerve fibers through the activation of rapid, calcium-permeable, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors. Synaptic responses are shaped by the unusual biophysical characteristics of octopus cells. Octopus cells have very low input resistances (about 7 M Omega), and short time constants (about 200 microsec) as a consequence of the activation at rest of a hyperpolarization-activated mixed-cation conductance and a low-threshold, depolarization-activated potassium conductance. The low input resistance causes rapid synaptic currents to generate rapid and small synaptic potentials. Summation of small synaptic potentials from many fibers is required to bring an octopus cell to threshold. Not only does the low input resistance make individual excitatory postsynaptic potentials brief so that they must be generated within 1 msec to sum but also the voltage-sensitive conductances of octopus cells prevent firing if the activation of auditory nerve inputs is not sufficiently synchronous and depolarization is not sufficiently rapid. In vivo in cats, octopus cells can fire rapidly and respond with exceptionally well-timed action potentials to periodic, broadband sounds such as clicks. Thus both the anatomical specializations and the biophysical specializations make octopus cells detectors of the coincident firing of their auditory nerve fiber inputs.

Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency.

1. Encoding temporal features of the acoustic waveform is an important attribute of the auditory system. Auditory nerve (AN) fibers synchronize or phase-lock to low-frequency tones and transmit this temporal information to cells in the anteroventral cochlear nucleus (AVCN). Phase-locking in the AVCN is usually reported to be similar to or weaker than in the AN. We studied phase-locking in axons of the trapezoid body (TB), which is the output tract of the AVCN, and found, to our surprise, that most TB axons exhibited enhanced synchronization compared with AN fibers. 2. Responses from axons in the TB of the cat were obtained with horseradish peroxidase (HRP)- or Neurobiotin-filled micropipettes or metal microelectrodes. A series of short tone bursts at increasing sound pressure level (SPL) was presented at the characteristic frequency (CF) of the fiber and phase-locking was quantified with the vector strength R at each SPL. For each fiber the maximum R value (Rmax) was then determined. 3. Low-frequency fibers in the TB showed very precise phase-locking: Rmax values could approach 0.99. For the majority of fibers (33/44, 75%) with CF < 700 Hz, Rmax was > or = 0.9 and therefore higher than is ever observed in the AN. We define such fibers as "high-sync." Most of these fibers also entrained to the stimulus, i.e., they fired a precisely timed action potential to almost every stimulus cycle. Some fibers showed perfect entrainment, with maximum discharge rates equaling the stimulus frequency. 4. To exclude the possibility that stimulus paradigms or acoustic and recording equipment were the source of this enhancement, we obtained additional data on low-frequency AN fibers using the same experimental protocol as in our TB experiments. These AN data agree well with published reports. 5. The morphological class of some of the cells studied was identified on the basis of anatomic features revealed by intra-axonal injection of HRP or Neurobiotin. Labeled low-CF axons (N = 7), which were all high-sync, originated from AVCN bushy cells: five were globular and two were spherical bushy cell axons. 6. Spontaneous rate of high-sync fibers covered a range from 0 to 176 spikes/s but were biased toward low values (mean 16 spikes/s). Responses to broadband clicks and sinusoidally amplitude-modulated signals provided additional evidence of improved timing properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Receptive fields and binaural interactions for virtual-space stimuli in the cat inferior colliculus.

Sound localization depends on multiple acoustic cues such as interaural differences in time (ITD) and level (ILD) and spectral features introduced by the pinnae. Although many neurons in the inferior colliculus (IC) are sensitive to the direction of sound sources in free field, the acoustic cues underlying this sensitivity are unknown. To approach this question, we recorded the responses of IC cells in anesthetized cats to virtual space (VS) stimuli synthesized by filtering noise through head-related transfer functions measured in one cat. These stimuli not only possess natural combinations of ITD, ILD, and spectral cues as in free field but also allow precise control over each cue. VS receptive fields were measured in the horizontal and median vertical planes. The vast majority of cells were sensitive to the azimuth of VS stimuli in the horizontal plane for low to moderate stimulus levels. Two-thirds showed a "contra-preference" receptive field, with a vigorous response on the contralateral side of an edge azimuth. The other third of receptive fields were tuned around a best azimuth. Although edge azimuths of contra-preference cells had a broad distribution, best azimuths of tuned cells were near the midline. About half the cells tested were sensitive to the elevation of VS stimuli along the median sagittal plane by showing either a peak or a trough at a particular elevation. In general receptive fields for VS stimuli were similar to those found in free-field studies of IC neurons, suggesting that VS stimulation provided the essential cues for sound localization. Binaural interactions for VS stimuli were studied by comparing responses to binaural stimulation with responses to monaural stimulation of the contralateral ear. A majority of cells showed either purely inhibitory (BI) or mixed facilitatory/inhibitory (BF&I) interactions. Others showed purely facilitatory (BF) or no interactions (monaural). Binaural interactions were correlated with azimuth sensitivity: most contra-preference cells had either BI or BF&I interactions, whereas tuned cells were usually BF. These correlations demonstrate the importance of binaural interactions for azimuth sensitivity. Nevertheless most monaural cells were azimuth-sensitive, suggesting that monaural cues also play a role. These results suggest that the azimuth of a high-frequency sound source is coded primarily by edges in azimuth receptive fields of a population of ILD-sensitive cells.