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We have previously shown that mice lateral superior olive (LSO) neurons exhibit a large hyperpolarization-activated current (Ih), and that hyperpolarization-activated cyclic-nucleotide-gated type 1 channels are present in both the soma and dendrites of these cells. Here we show that the dendritic Ih in LSO neurons modulates the integration of multiple synaptic inputs. We tested the LSO neuron’s ability to integrate synaptic inputs by evoking excitatory post-synaptic potentials (EPSPs) in conjunction with brief depolarizing current pulses (to simulate a second excitatory input) at different time delays. We compared LSO neurons with the native Ih present in both the soma and dendrites (control) with LSO neurons without Ih (blocked with ZD7288) and with LSO neurons with Ih only present perisomatically (ZD7288+ computer-simulated Ih using a dynamic clamp). LSO neurons without Ih had a wider time window for firing in response to inputs with short time separations. Simulated somatic Ih (dynamic clamp) could not reverse this effect. Blocking Ih also increased the summation of EPSPs elicited at both proximal and distal dendritic regions, and dramatically altered the integration of EPSPs and inhibitory post-synaptic potentials. The addition of simulated peri-somatic Ih could not abolish a ZD7288-induced increase of responsiveness to widely separated excitatory inputs. Using a compartmental LSO model, we show that dendritic Ih can reduce EPSP integration by locally decreasing the input resistance. Our results suggest a significant role for dendritic Ih in LSO neurons, where the activation ⁄ deactivation of Ih can alter the LSO response to synaptic inputs.

In mammals, spatial hearing is supported by evaluation of two types of binaural disparities, interaural time difference (ITD) and interaural level difference (ILD), which is performed by auditory neurons in the superior olivary complex. Using a complex auditory model, which includes a binaural evaluation stage, the output of binaural neurons from medial and lateral superior olive is simulated and quantitatively compared with available experimental data. Both binaural disparities are evaluated using detection of coincidence of spikes arriving from the two channels: in case of ITD, the coincidence of two excitatory spikes is detected; in case of ILD, the coincidence of one excitatory and one inhibitory spike is detected. It is shown that using a physiologically realistic set of parameters, evaluation of both ITD and ILD based on coincidence detection is capable of reproducing the observed neuronal responses. Furthermore, the model is shown to qualitatively reproduce the just-noticeable differences of binaur...

Roberts and Meredith (1992) wrote: “For more than forty years, the efferent supply to the mammalian ear provided by the olivocochlea bundle has been an enigma,” and this is still true today, in particular for the development of efferents. The inner ear efferents are so unique in their physiology, axonal course, and distribution that this adds to the mystery of their role in hearing and balance (Christopher Kirk and Smith 2003). However, analyzing the development of the vestibulocochlear efferent system may not only give us new insight into the development of this system but may also help to understand how the distribution and neurochemcial properties of the adult vestibulocochlear efferent system all come about.

1. The sensitivity of lateral superior olive (LSO) neurons to interaural time differences was examined in an in vitro brain slice preparation. Brain slices, 400-500 microns, were taken through the superior olivary complex of C57 BL/6J mice and were maintained in an oxygenated saline solution for single-unit recording. Both extracellular and intracellular recordings were made with glass pipettes filled with 4 M potassium acetate. Responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located ipsilateral or contralateral to the olivary complex. Binaural interactions were studied by manipulating the timing and intensity of paired ipsilateral and contralateral pulses. 2. In extracellular recordings, stimulation of the ipsilateral trapezoid body usually elicited a single action potential, whereas stimulation of the contralateral trapezoid body failed to produce a spike response. Bilateral stimulation resulted in the complete suppression of the evoked spike, indicating the presence of a contralateral inhibitory effect. The degree of inhibition depended on the interpulse interval between ipsilateral and contralateral stimulation. With sufficiently large ipsilateral lead times, the probability of eliciting an extracellular spike was 1.0. As the interpulse interval was gradually shifted to reduce the ipsilateral lead time, the response probability precipitously dropped to 0.0. Most neurons could be completely suppressed by simultaneous stimulation. The dynamic range, defined as the range of interpulse intervals over which response probability changed from 0.9 to 0.1, was between 125 and 225 microseconds for most cells tested. 3. With increasing contralateral lead times, the extracellularly recorded spike was eventually released from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the development of dendritic arbors in a central auditory nucleus in the Mongolian gerbil, the lateral superior olive (LSO). The morphology of these arbors has been shown to vary with tonotopic position in adults, with high frequency neurons having a more restricted field. In the present study, qualitative observations were made on horseradish peroxidase-filled neurons from animals 1–11 days postnatal, and quantitative results were obtained from Golgi-impregnated material from animals 10 days postnatal and older. The tonotopic position of each cell was computed as a percent of the total distance along the LSO. The dendritic arbor high frequency neurons became spatially constrained along the frequency axis during the 3rd postnatal week, while those in the low frequency region retained a broader arborization into adulthood. This refinement was correlated with a decrease in total dendritic length and the number of branch points per neuron, particularly in the high frequency projection region. The distribution of octave bandwidths to which single LSO neurons responded in 13–16 day animals showed a similar course of maturation across the tonotopic axis: high frequency neurons responded to a larger number of octaves, and with greater variability, than those in adults. These data suggest that a specific alteration in dendrite morphology, which occurs after the onset of response to airborne sound, may contribute to adult frequency selectivity.

1. Previous studies of the superior olive of echolocating bats suggest that the lateral superior olive (LSO) retains the same structure and function as in other mammals but that the medial superior olive (MSO) is different in structure and possibly also in function. The present study is an examination of this idea in Pteronotus parnellii, a bat that has a large and well-defined MSO. 2. Using pure tones presented via earphones, we obtained data on frequency tuning for 60 single units and 96 multiunits in LSO and 94 single units and 154 multiunits in MSO. Of these we also obtained binaural response characteristics from 55 single units in LSO and 72 single units in MSO. 3. LSO and MSO each have a complete tonotopic representation, arranged in a sequence similar to that of other mammals studied. However, in both LSO and MSO there is an expanded representation of the frequencies around 60 kHz, the main frequency component of the bat's echolocation call; there is another expanded representation of the range around 90 kHz, the third harmonic of the call. The expansion of these frequency ranges suggests that the functions of LSO and MSO in Pteronotus are related to echolocation behavior. 4. The binaural characteristics of cells in LSO were essentially the same as those seen in other mammals. Most LSO units (93%) were excited by the ipsilateral ear and inhibited by the contralateral ear. The responses of nearly all LSO units were completely suppressed when the sound level at the two ears was equal. 5. The binaural characteristics of cells in MSO were different from those in nonecholocating mammals. Most MSO units (72%) were excited by the contralateral ear but were neither excited nor inhibited by the ipsilateral ear. Of the remaining units, 21% were excited by the contralateral ear and inhibited by the ipsilateral ear, and only 6% were excited by both ears. 6. The temporal discharge patterns of units in MSO differed from the tonic response pattern seen in LSO. Most MSO units had phasic response patterns, with a few spikes at the onset or offset of the stimulus; the response often changed from ON to OFF depending on stimulus frequency. 7. The results support the idea that in evolution LSO has remained unchanged, whereas MSO has undergone adaptation. The function of LSO in Pteronotus seems to be identical to that in other mammals, i.e., analysis of interaural sound level differences to derive azimuthal location. The function of MSO in Pteronotus must be different from that in nonecholocating mammals.(ABSTRACT TRUNCATED AT 400 WORDS)

The Lateral Superior Olive (LSO) codes for interaural intensity difference (IID), a cue used for sound localization. Between birth and maturation, the LSO undergoes plasticity driven by input neurons activity. During this developmental phase, a number of inputs are pruned out leading to a refinement of the frequency tuning. The goal of this paper is to show that, using a physiologically plausible network architecture and neuronal model, the activity dependent plasticity of the LSO can be modeled using Spike-Timing Dependent Plasticity (STDP). In particular, we show that the time properties of STDP coupled with the fact that the frequency axis in the LSO can be considered as a delay axis leads to the observed tonotopical map refinement. The response of both the individual neurons as well as population are shown to be in accordance with data taken from physiological analysis.

One way to localize sounds is to measure differences in sound intensity at the two ears. This comparison is made in the lateral superior olive, where signals from both ears converge. Magnusson et al. in this issue of Neuron show that dendritic GABA release can regulate this comparison, which may allow animals localizing sounds to adapt to listening conditions.

Bats, like other mammals, are known to use interaural intensity differences (IID) to determine azimuthal position. In the lateral superior olive (LSO) neurons have firing behaviors which vary systematically with IID. Those neurons receive excitatory inputs from the ipsilateral ear and inhibitory inputs from the contralateral one. The IID sensitivity of a LSO neuron is thought to be due to delay differences between the signals coming from both ears, differences due to different synaptic delays and to intensity-dependent delays. In this paper we model the auditory pathway until the LSO. We propose a learning scheme where inputs to LSO neurons start out numerous with different relative delays. Spike timing-dependent plasticity (STDP) is then used to prune those connections. We compare the pruned neuron responses with physiological data and analyse the relationship between IID’s of teacher stimuli and IID sensitivities of trained LSO neurons.

Mammals are known to use Interaural Intensity Difference (IID) to determine azimuthal position of high frequency sounds. In the Lateral Superior Olive (LSO) neurons have firing behaviours which vary systematicaly with IID. Those neurons receive excitatory inputs from the ipsilateral ear and inhibitory inputs from the contralateral one. The IID sensitivity of a LSO neuron is thought to be due to delay differences between both ears, delays due to different synaptic delays and to intensity-dependent delays. In this paper we model the auditory pathway until the LSO. Inputs to LSO neurons are at first numerous and differ in their relative delays. Spike Timing-Dependent Plasticity is then used to prune those connections. We compare the pruned neuron responses with physiological data and analyse the relationship between IID-s of teacher stimuli and IID sensitivities of trained LSO neurons., {"references":["","Pickles, J.O.: An introduction to the physiology of hearing, London: Academic Press (1982)","Tollin, D.J.: The Lateral Superior Olive: a Functional Role in Sound Source Localization. Neuroscientist, vol. 9(2) (2003) 127-143","Schaette, R., Gollisch T., Herz, A.: Spike-train vairability of auditory neurons in vivo: dynamic responses follow predicitions from constant stimuli. J. Neurophysiology, vol. 93 (2005) 3270-3281","Park, T.J., Grothe, B., Park, G.D., Schuller, G., Koch, U.: Neural delays shape selectivity to interaural differences in the lateral superior olive. J. Neuroscience, vol. 16(20) (1996) 6554-6566","Park, T.J, Monsivais P., and Park, G.D.: Processing of interaural intensity differences in the LSO: role of the interaural threshold differences. J. Neurophysiology, vol. 77 (1997) 2863-2878","Heil, P., Irvine, D.: First-spike timing of auditory-nerve fibers and comparison with auditory cortex. Neurophy., vol. 78 (1997) 2438-2454","Park, T.J.: Latency as a function of intensity in auditory neurons: influences of central processing. Hear. Res., vol. 148 (2000) 107-123","van Hemmen, J.L., Leibold C.: Spiking neurons learning phase delays: how mammals may develop auditory time difference sensitivity. Physical Review Letters, Vol. 94. (2005)","Sanes, D.H., Friauf, E.: Development and influence of inhibition in the lateral superior olivary nucleus. Hearing Research, vol. 147, (2000) 46-58\n[10] Sanes, D.H.: An in vitro analysis of sound localization mechanisms in the gerbil lateral superior olive. J. Neuroscience, vol. 10, (1990) 3494-3506\n[11] Gestner, W., Kistler, W.N.: Spiking neuron models. Cambridge University Press, Cambridge (2002)\n[12] The networks have been simulated using the Csim Toolbox available at http://www.lsm.tugraz.at/csim The parameters of the LIF neurons are: Rm=1M╬®, ¤äm=20ms, Vthresh=-0.045V, Vresting=-0.06V, Vreset=- 0.06V, Vinit=-0.06V, Trefract=1ms. The parameters of the synapses are ¤äContra=2ms, ¤äIpsi=0.5ms, Wmax=1e-4. The parameters of the windows are A+=2/3, B+=0.25, ╬À+=50e-6, ¤ä+ 0 =1/10ms, ¤ä+ 1 =1/200ms, ¤ä+ 2 =1/2ms, s*+=-1/800ms, A−=0.7, B−=0.25, ╬À−=50e-6, ¤ä−0 =1/5ms, ¤ä−1 =1/20ms, ¤ä−2 =1/2ms, s*−=-0.1ms."]}

This modeling study examines the possible functional roles of two hyperpolarization-activated conductances in lateral superior olive (LSO) principal neurons. Inputs of these LSO neurons are transformed into an output, which provides a firing-rate code for a certain interaural sound intensity difference (IID) range. Recent experimental studies have found pharmacological evidence for the presence of both the G KIR conductance as well as the inwardly rectifying outward G KIR conductance in the LSO. We addressed the question of how these conductances influence the dynamic range (IID versus firing rate). We used computer simulations of both a point-neuron model and a two-compartmental model to investigate this issue, and to determine the role of these conductances in setting the dynamic range of these neurons. The width of the dynamic regime, the frequency-current (f-I) function, first-spike latency, subthreshold oscillations and the interplay between the two hyperpolarization activated conductances are discussed in detail. The in vivo non-monotonic IID-firing rate function in a subpopulation of LSO neurons is in good correspondence with our simulation predictions. Two compartmental model simulation results suggest segregation of G h and G KIR conductances on different compartments, as this spatial configuration could explain certain experimental results.

Compared to our current knowledge of neuronal excitation, little is known about the development and maturation of inhibitory circuits. Recent studies show that inhibitory circuits develop and mature in a similar way like excitatory circuit. One such similarity is the development through excitation, irrespective of its inhibitory nature. Here in this current study, I used the inhibitory projection between the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO) as a model system to unravel some aspects of the development of inhibitory synapses. In LSO neurons of the rat auditory brainstem, glycine receptor-mediated responses change from depolarizing to hyperpolarizing during the first two postnatal weeks (Kandler and Friauf 1995, J. Neurosci. 15:6890-6904). The depolarizing effect of glycine is due to a high intracellular chloride concentration ([Cl-]i), which induces a reversal potential of glycine (EGly) more positive than the resting membrane potential (Vrest). In older LSO neurons, the hyperpolarizing effect is due to a low [Cl-]i (Ehrlich et al., 1999, J. Physiol. 520:121-137). Aim of the present study was to elucidate the molecular mechanism behind Clhomeostasis in LSO neurons which determines polarity of glycine response. To do so, the role and developmental expression of Cl-cotransporters, such as NKCC1 and KCC2 were investigated. Molecular biological and gramicidin perforated patchclamp experiments revealed, the role of KCC2 as an outward Cl-cotransporter in mature LSO neurons (Balakrishnan et al., 2003, J Neurosci. 23:4134-4145). But, NKCC1 does not appear to be involved in accumulating chloride in immature LSO neurons. Further experiments, indicated the role of GABA and glycine transporters (GAT1 and GLYT2) in accumulating Cl- in immature LSO neurons. Finally, the experiments with hypothyroid animals suggest the possible role of thyroid hormone in the maturation of inhibitory synapse. Altogether, this thesis addressed the molecular mechanism underlying the Cl- regulation in LSO neurons and deciphered it to some extent. Die Rolle von Plasmamembran -Transportern beim Chlorid-Gleichgewicht in Neuronen der auditorischen Hirnstamm während der Entwicklung

The superior olivary complex (SOC) is a conspicuous structure in the mammalian central auditory system. It is located ventrally in the pontine brain stem underneath the cerebellum and consists of several third-order nuclei. The general organization of the SOC is illustrated in Figure 3.1A. Usually three principal SOC nuclei are identified (for abbreviations, see list at end of chapter), the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB; Irving and Harrison 1967; for review see Schwartz 1992; see also Reuss 2000). These principal nuclei are surrounded by periolivary regions: the superior paraolivary nucleus (SPN), the lateral nucleus of the trapezoid body (LNTB), and the ventral nucleus of the trapezoid body (VNTB). In the rodent brain, the nomenclature occasionally refers to the LNTB and VNTB as the lateroventral (LVPO) and medioventral periolivary region (MVPO), respectively (Osen et al. 1984; Thompson and Thompson 1991). In cats and bats, a dorsomedial periolivary nucleus (DMPO) has been described and appears to be equivalent to the SPN of the rodent brain (Schofield and Cant 1991; Schwartz 1992; Ostapoff et al. 1997; Grothe and Park 2000). Rostrally and caudally to the SOC proper, two additional areas are located that are generally called the rostral and the caudal periolivary region (RPO and CPO, respectively).

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.

Sound location in azimuth is signaled by differences in the times of arrival (interaural time difference, ITDs) and the amplitudes (interaural level differences, ILDs) of the stimuli at the ears. Psychophysical studies have shown that low- and high-frequency sounds are localized based on ITDs and ILDs, respectively, suggesting that dual mechanisms mediate localization. The anatomical and physiological bases for this “duplex theory” of localization are found in the medial (MSO) and lateral (LSO) superior olives, two of the most peripheral sites in the ascending auditory pathway receiving inputs from both ears. The MSO and LSO are believed to be responsible for the initial encoding of ITDs and ILDs, respectively. Here the author focuses on ILDs as a cue to location and the role of the LSO in encoding ILDs. Evidence from disparate fields of study supports the hypothesis that the LSO is the initial ILD processor in the mammalian auditory system. NEUROSCIENTIST 9(2): 127–143, 2003.

The fundamental questions of sensory neuroscience are how neurons encode information and how neurons extract (process) information. For example, in the auditory system, sound location is determined by a combination of amplitude and time cues. The Lateral Superior Olive (LSO), one of the first nuclei to receive inputs from both ears, is thought to extract high-frequency localization information based on interaural level difference (ILD) and interaural time difference (ITD) cues. However, while the optimal localization processing system produces the same response for the same ILD regardless of source level,1 LSO responses are affected by source level.2 This sensitivity questions the presumption that the LSO is strictly an angle processor, and suggests that the LSO may be coding other stimulus features such as sound level. We have used a new analysis technique to analyze the significance of the LSO sensitivity to sound level compared to that of an optimal angle processor. We also examined the processing of two features: azimuthal angle and source level by the LSO network by comparing the response sensitivity of network inputs with that of its outputs.

Short-term adaptation was examined in single unit recordings from 113 superior olive neurons of anaesthetized 3- to 6-month-old Long-Evans rats. Responses to an equal intensity BF probe tone presented 1 ms after an 'adapting' BF tone were adapted by 56.3 +/- 2.6% (mean +/- S.E.) compared to responses at a 512 ms delay. The rapid decrease in discharge rate during adapting tones often approximated exponential time courses with time constants of less than 20 ms. The recovery from adaptation was exponential with time constants of 106 +/- 20.0 ms. The magnitude of adaptation and time course of recovery following monaural stimulation of binaurally excited (EE) neurons were not significantly different in both input pathways. Additionally, in 60% of EE neurons, an 'adapting' tone presented to one ear reduced subsequent responses to probe tones presented to the opposite ear. Binaural stimulation resulted in equal or greater adaptation of responses than monaural stimulation of either ear. The recovery of binaural excitatory responses generally followed a time course between recovery functions for ipsilateral and contralateral monaural stimuli. Lateral Superior Olive (LSO) neurons encode sound source location through the interaction of ipsilateral excitation and contralateral inhibition (IE). Ipsilaterally driven excitatory responses in LSO neurons exhibited the greatest magnitude of adaptation (68.5 +/- 21.1%). Adaptation of inhibition was observed in over half of IE neurons. Responses of LSO neurons to binaural BF probe stimuli were greatest immediately after a 200 ms BF 'inhibitory adapting' stimulus to the contralateral ear, and decreased with greater interstimulus delays. Responses to binaural stimulation were constant after prior binaural adaptation, when the magnitude and recovery of adaptation to monaural stimuli were similar for excitation and inhibition (8/25 IE cells). The functional significance and possible sites of adaptation processes are discussed.

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.

Computational models in this chapter are defined to include models that lead to explicit, quantitative predictions for the phenomena that are being modeled. They may be posed purely in terms of the information that is available for the task, in which case the computed predictions are evaluated using information-theoretical or other statistical communication theory techniques, or they may be posed in terms of mechanisms or algorithms. Both types of computational models are included in this chapter. We do not include models that have been suggested but not evaluated or models which are not sufficiently explicit to allow precise predictions.

We have examined the projection from the lateral superior olive (LSO) to the inferior colliculus (IC) in the ferret, with particular interest in the laterality of the projection and in the effects of unilateral cochlear removal in infancy. Large or small deposits of the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made in the IC of anesthetized adult ferrets that either were normally hearing or had been unilaterally deafened in infancy (P5 or P25). After 2 days, the ferrets were perfused, and frontal sections of the brainstem were treated with tetramethyl benzidine. For large deposits of WGA-HRP, equal numbers of labelled neurons were found evenly spread through both LSOs. Smaller deposits of WGA-HRP produced four results that contrasted with previous reports on the cat. First, many more labelled neurons were found in the contralateral than in the ipsilateral LSO. Second, the relative number of labelled neurons in each LSO was independent of whether the deposits were in the ventral or in the dorsal IC. Third, the total number of labelled LSO neurons was independent of whether the deposits were in the ventral or in the dorsal IC. Fourth, the proportion of ipsilateral to contralateral labelled neurons was slightly higher in the medial LSO than in the lateral LSO. Ventral IC deposits resulted in more labelled neurons in the medial LSO, and dorsal IC deposits resulted in more labelled neurons in the lateral LSO, as expected. Neonatal cochlear removal did not change any of these results. We conclude that, in the ferret, the organization of the crossed and uncrossed projections from the LSO to the IC differs from that of the cat, and any similarity with the optic chiasm is not obvious.

A vital function of the auditory system in all vertebrates is to identify sounds that are important for social interactions, predation and predator avoidance. Examples of these behaviorally important sounds are communication signals of conspecifics, noises made by movements of other animals and highly specialized species-specific sounds such as the biosonar signals used by echolocating bats. Identification of many behaviorally important sounds, especially those made by prey or predators, must occur rapidly to activate other neural systems that produce a motor response. Many biologically important sounds are characterized by simple temporal features, such as duration of the sound or its components, direction of a frequency sweep, or the rate of modulation in sounds that periodically change in frequency or amplitude. Many sounds are further characterized by complex sequences of elements that follow a specific order over time.

The purpose of this study was to investigate quantitatively the distribution of calcitonin gene-related peptide (CGRP)-positive neurons within the superior olivary complex (SOC) at various postnatal ages. In the lateral superior olive (LSO), most if not all, CGRP-positive cells correspond to the cholingeric portion of the lateral olivocochlear system which innervates the cochlea. Brains from 1-day old (P1) through juvenile (P30) hamsters were used. At all ages, CGRP-positive neurons were seen throughout the various nuclei of the SOC. There was a dramatic shift in the distribution of CGRP-positive neurons from being predominantly periolivary to being predominantly confined within the LSO. The number of CGRP-positive neurons clearly increased as a function of increasing age. At the earliest postnatal ages, the LSO contained few if any immunostained cells, whereas at later ages the LSO contained the majority (greater than 70%) of the immunostained cells. Assuming that these CGRP-positive cells within the LSO correspond to olivocochlear neurons, these data suggest that in hamsters the lateral olivocochlear system may be immature at birth up until the second postnatal week.

The duplex theory posits that low‐ and high‐frequency sounds are localized using two different acoustical cues, interaural time delays (ITDs) and interaural level differences (ILDs), respectively. Psychophysical data have generally supported the theory for pure tones. Anatomical and physiological studies have revealed two parallel brainstem pathways that appear to encode ITDs and ILDs separately. ITDs are extracted by medial superior olive neurons. ILDs are extracted by lateral superior olive (LSO) neurons. ILD‐sensitive neurons are also found in the inferior colliculus (IC). ILDs are a complex function of both source location and frequency such that lower and higher frequencies exhibit smaller and larger ILDs, respectively. LSO and IC neurons encode ILDs for high‐frequency sounds where the cues are physically available, but there are discrepancies regarding low‐frequency neurons. Although acoustically, low‐frequency ILDs are small, humans are sensitive to them and physiological studies have found low‐frequency neurons in the LSO and IC that could encode them. Here the hypothesis that low‐frequency ILDs are useful when sound source distance is varied is explored. These data demonstrate that a population of IC neurons is sufficient to encode the range of acoustic ILDs that would be experienced as a joint function of source location and distance.

Signal processing by neurons in the lateral superior olive, an auditory brain stem nucleus, is described based on the statistical analysis of extracellularly recorded single-unit data.

1. Preliminary to extending a point process model of lateral superior olive (LSO) unit activity to describe the units' binaural responses, the statistical properties of their discharges to binaural tone bursts were studied. The hypothesis that stimulation of the contralateral ear results in the simple reduction of the ipsilateral input was also examined. Single-unit activity was recorded extracellularly from the LSO of the anesthetized cat. The sustained discharges to characteristic frequency (CF) tone bursts presented simultaneously to the two ears were examined to determine whether the fine temporal (statistical) properties of these discharges differed from those of the discharges elicited by stimulating the ipsilateral ear alone. 2. The major effect of simultaneously stimulating the contralateral ear was the inhibition (i.e., the reduction in the mean discharge rate) of the sustained discharges to the ipsilateral control stimulus. The temporal pattern of discharges to the ipsilateral stimulus was also affected by stimulation of the contralateral ear. The discharges to binaural stimulation were more irregular in pattern: they often produced bimodal or multimodal interval histograms where unimodal interval histograms had been produced by the discharges to the ipsilateral control stimulus alone. The hazard function, an estimate of the unit recovery function, also often differed in form for the binaural and monaural discharges. 3. The binaural discharges could be distinguished from an ipsilaterally elicited discharge of comparable mean rate: there was a greater incidence of “short” interspike intervals in the binaural discharge. These short interspike intervals occurred most frequently in the discharges to the ipsilateral control stimulus alone and infrequently in the discharges to an ipsilateral stimulus that produced a mean rate similar to that of the binaural discharge. Thus the dead time estimates derived from the binaural discharges were more similar to the estimates derived from the ipsilateral control discharges than to those derived from the comparable-rate ipsilaterally elicited discharges. 4. Although the measures of the recovery properties of LSO unit discharges differed under monaural and binaural stimulus conditions, the serial dependence observed between successive interspike intervals in the binaurally elicited discharges was similar to that in the ipsilaterally elicited discharges. The conditional mean function, an estimate of the serial dependence or unit shifting function, did not differ greatly in form for the monaural and binaural discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

Auditory evoked potentials were recorded in patients undergoing neurosurgical operations to manage cranial nerve dysfunctions. Recordings were made intra-operatively from the distal portion of the eighth nerve, from the entrance of the eighth nerve into the brain stem, and from a site overlying the superior olivary complex (rostral and medial to the entrance of the eighth nerve). The potentials at the three different loci showed characteristic differences: the responses recorded at the entrance of the eighth nerve into the brain stem showed three peaks about 1 ms apart. The earliest peaks had longer latencies than did those recorded at a distal locus on the eighth nerve, which is consistent with what we know about propagation of nerve impulses in the auditory nerve. The responses recorded on the brain stem, rostral-medial to the eighth nerve, also showed three peaks but the amplitude of the third peak was greater than those of the other two. It is assumed that the first peak originates in the auditory nerve, the second peak in the cochlear nucleus, and the third peak in the lateral superior olive. The latencies of these peaks match the latencies of peaks II, III, and IV of scalp-recorded brain stem evoked potentials.

A general point process theory is developed to describe discharges recorded from lateral superior olivary units of the cat responding to ipsilaterally presented tone bursts and continuous tones. Statistical analysis of the stationary portion of the sequence of interspike intervals demonstrated that, for most units, the duration of each interval is statistically dependent only on the duration of the previous interval. A specific point process model is derived based on this analysis to describe the measured serial dependence as well as the deadtimes observed in interval histograms. The statistical dependence is well described as a shift of the interspike interval distribution, the shift depending on the duration of the previous interval. This model is then used to simulate the initial chopping in the tone burst responses. It is concluded that chopping responses and serial dependence do not result from properties of the unit's inputs; rather, they are consequences of the inherent characteristics of the unit.

We have investigated developmental alterations in the tonotopic projection of the gerbil lateral superior olive. Single neurons were characterized in the frequency domain and the recording site marked with fast green. Transverse tissue sections from the auditory brainstem of each animal were visualized with a video-equipped microscope, and the image was digitized for subsequent alignment. The three-dimensional display indicated little variation in the rostrocaudal axis, allowing us to collapse the data into a two-dimensional tonotopic map. The tonotopic map was found to change with age such that the characteristic frequency of neurons in a given anatomical location became successively higher during development. These results are consistent with the hypothesis that the place code gradually shifts in the developing cochlea.

In the cochlear nuclei nine different cell types are distinguished on the basis of Nissl preparations. Only three of these cell types are presented here. The large and small spherical cells are innervated from the ascending cochlear branches by means of typical bulbs of Held. The former cell group is apparently supplied only from the apical and middle part of the cochlea and projects bilaterally on the medial superior olive, while the latter group seems to be supplied from the entire cochlea and projects on the lateral superior olive on the same side. The octopus cells are innervated from the descending cochlear branches by means of small ring-shaped boutons. The axons of these cells run in the intermediate acoustic stria and terminate probably in the retroolivary and medial preolivary nuclei on both sides. The function of the three types of cells is discussed.

The course and termination of the stria of Monakow and stria of Held were studied with Nauta-Gygax technique following a localized lesion of the dorsal cochlear nucleus in the cat. A dense preterminal degeneration within all homolateral primary cochlear nuclei and a tract of degenerated fibers crossing the restiform body dorsally were found. This tract divides in two branches forming the stria of Held and stria of Monakow. The stria of Held followed the course described by classical anatomists. In the homolateral side, the stria gave terminals to the medial and lateral preolivary nuclei, lateral superior olive nucleus and retro-olivary groups. In the contralateral side, preterminal degeneration was found in the medial preolivary nucleus and medial retro-olivary group. The stria of Monakow is essentially crossed pathway given numerous terminals to the contralateral dorsal retro-olivary group, rostral part of the lateral preolivary nucleus, the ventral and dorsal nuclei of the lateral lemniscus, and nucleus of the inferior colliculus.

Discharges were recorded extracellularly from single units localized in the lateral superior olive (LSO) of barbiturate anesthetized cats. The statistical properties of the unit discharges to monaurally presented tone bursts were determined. Increasing the stimulus level of an ipsilaterally presented tone burst produced an increase in the discharge rate and the emergence and growth of a time‐locked discharge pattern in the initial portion of the response. The initial time‐locked response was transient and was followed by a nontime‐locked sustained response. In the sustained portion, increasing stimulus level produced increases in rate and changes in the interspike interval statistics. Average rate and interval statistics were found to be systematically related. LSO units were differentiated on the basis of rate and pattern of their initial discharges into two main types: the fast and slow chopping units. An analysis of the results indicated that some aspects of response type differences may be related to input characteristics rather than to neuron response mechanisms.

Superposition of point processes has often been suggested as an abstract model for the generation of neural discharge patterns due to its simplicity (input spike trains are simply merged and then retransmitted by the model neuron). The properties of the superposition of two renewal processes are examined in relation to the properties of its components. A satisfactory condition is found so that the superposition of two renewal processes possesses negative serial dependence of interevent intervals. However, the imposition of a dead time of approximately the same duration as that of the components on their superposition process is shown to remove much of this dependence. Thus, the adequacy of the simple superposition of renewal processes as a model for discharge patterns from regions that are typified by negative serial dependence (such as the lateral superior olive) may be limited, but may suffice for the discharges of primary-like units.

Investigations in the cat, rat, and guinea pig have shown that two separate populations of neurons form the efferent innervation of the cochlea (Warr and Guinan, 1979; White and Warr, 1983; Strutz and Bielenberg, 1984). Auditory nerve fibers at the base of inner hair cells (IHC) are innervated by small neurons that are located in the region of the lateral superior olive (LSO) predominantly or exclusively on the ipsilateral side. In rat and guinea pig, these neurons are found within the LSO, in cat they are located close to the LSO mainly in its dorsal hilus. Because of the position of these neurons in the olivary complex it was called lateral system. Outer hair cells (OHC) receive their efferent innervation from a group of large neurons in several periolivary nuclei. This medial system is organized bilaterally in all species studied so far.

Phaseolus vulgaris leucoagglutinin (PHA-L), a kidney bean lectin used as an anterograde tracer, was iontophoretically injected into the posteroventral cochlear nucleus (PVCN) of guinea pigs. PHA-L-labelled fiber segments and their terminal specializations were observed within the ipsilateral lateral superior olive (LSO) thereby establishing the existence of an efferent neural pathway from PVCN to this nucleus. Furthermore, the pathway is topographically organized with dorsal regions of PVCN projecting to the medial limb and ventral regions projecting to the lateral limb of LSO.

The guinea pig lateral superior olive was examined immunocytochemically using antisera against enkephalin and choline acetyltransferase sequentially on the same sections. A colocalization of choline acetyltransferase-like and enkephalin-like immunoreactivities was found in cells of the lateral superior olive that give rise to the lateral system of olivocochlear efferents. Only choline acetyltransferase-like immunoreactivity was observed in the group of olivary nuclei that give rise to the medial group of olivocochlear fibers.