Ipsilateral Lateral Superior Olive Research Articles

The brainstem efferent acoustic chiasm in pigmented and albino rats

The present study examined whether structural peculiarities in the brain-efferent pathway to the organ of Corti may underlie functional differences in hearing between pigmented and albino individuals of the same mammalian species. Pigmented Brown-Norway rats and albino Wistar rats received unilateral injections of an aqueous solution of the retrograde neuronal tracer Fluorogold (FG) into the scala tympani of the cochlea to identify olivocochlear neurons (OCN) in the brainstem superior olivary complex. After five days, brains were perfusion-fixed and brainstem sections were cut and analyzed with respect to retrogradely labeled neurons. Intrinsic neurons of the lateral system were located exclusively in the ipsilateral lateral superior olive (LSO) in both groups. Shell neurons surrounding the LSO and in periolivary regions, which made up only 5–8% of all OCN, were more often contralaterally located in albino than in pigmented animals. A striking difference was observed in the laterality of neurons of the medial olivocochlear (MOC) system, which provided more than one third of all OCN. These neurons, located in the rostral periolivary region and in the ventral nucleus of the trapezoid body, were observed contralateral to 45% in pigmented and to 68% in albino animals. Our study, the first to compare the origin of the olivocochlear bundle in pigmented and albino rats, provides evidence for differences in the crossing pattern of the olivocochlear pathway. These were found predominantly in the MOC system providing the direct efferent innervation of cochlear outer hair cells. Our findings may account for the alterations in auditory perception observed in albino mammals including man.

Can auditory brainstem and midbrain processing of interaural level difference cues really explain perceptual performance?

Neurons in the lateral superior olive (LSO) are believed to be involved in processing of interaural level difference (ILD) cues for sound localization. However, the ILD-tuning of LSO neurons varies with the absolute sound pressure levels (SPLs) at the two ears, in contrast to the relatively robust perceptual processing of ILD cues at different absolute SPLs. Tsai et al. (J. Neurophysiol. 2010) proposed that if some inferior colliculus (IC) neurons compute the difference between the contralateral and ipsilateral LSO outputs, the dependencies on absolute SPLs could be canceled out. However, they only considered pure-tone stimulation of single neurons at their characteristic frequencies and at relatively low SPLs. In this study, we evaluated the hypothesis of Tsai and colleagues using computational models of populations of auditory nerve, LSO and IC neurons consistent with Tsai and colleagues’ proposal. Predictions from two different neural decoder algorithms applied to LSO and IC model outputs indicate that discharge-rate saturation and spread of excitation in the auditory nerve lead to even greater SPL-dependence of ILD coding across a population of LSO neurons than is apparent in single neurons, and the IC differencing operation proposed by Tsai and colleagues does relatively little to ameliorate this problem.

Embryonic assembly of auditory circuits: spiral ganglion and brainstem

During early development, peripheral sensory systems generate physiological activity prior to exposure to normal environmental stimuli. This activity is thought to facilitate maturation of these neurons and their connections, perhaps even promoting efficacy or modifying downstream circuitry. In the mammalian auditory system, initial connections form at embryonic ages, but the functional characteristics of these early neural connections have not been assayed. We investigated processes of embryonic auditory development using a whole-head slice preparation that preserved connectivity between peripheral and brainstem stations of the auditory pathway. Transgenic mice expressing fluorescent protein provided observation of spiral ganglion and cochlear nucleus neurons to facilitate targeted electrophysiological recording. Here we demonstrate an apparent peripheral-to-central order for circuit maturation. Spiral ganglion cells acquire action potential-generating capacity at embryonic day 14 (E14), the earliest age tested, and action potential waveforms begin to mature in advance of comparable states for neurons of the ventral cochlear nucleus (VCN) and medial nucleus of the trapezoid body (MNTB). In accordance, auditory nerve synapses in the VCN are functional at E15, prior to VCN connectivity with the MNTB, which occurs at least 1 day later. Spiral ganglion neurons exhibit spontaneous activity at least by E14 and are able to drive third-order auditory brainstem neurons by E17. This activity precedes cochlear-generated wave activity by 4 days and ear canal opening by at least 2 weeks. Together, these findings reveal a previously unknown initial developmental phase for auditory maturation, and further implicate the spiral ganglion as a potential controlling centre in this process.

Patterning of multiple layered projections to the auditory midbrain prior to experience

The precise arrangement of patterned inputs into discrete functional domains is a common organizational feature of primary sensory structures. While the specific organization of patterned connections has been well documented in the visual and somatosensory systems, comparatively little is known about the arrangement of neighboring afferent patterns in the emerging auditory system. Here we report early projection specificity for multiple converging inputs to the rat central nucleus of the inferior colliculus (ICC). Afferents arising from the dorsal cochlear nucleus (DCN), the dorsal nucleus of the lateral lemniscus (DNLL), and the lateral superior olive (LSO) establish discernible axonal layers a week prior to experience. By hearing onset, contralateral DCN and contralateral LSO layers are clearly defined and segregated from contralateral DNLL terminal zones. Layering of the ipsilateral LSO projection, on the other hand, exhibits considerable spatial overlap with the contralateral DNLL pattern. This fine laminar structure of interdigitating and overlapping inputs likely underlies the complex signal processing performed in the auditory midbrain and may serve as a model system for examining competitive interactions between neighboring excitatory and inhibitory projections early in development.

Anatomical plasticity in brainstem auditory nuclei following unilateral ablation of the inferior colliculus in neonatal rats

Anatomical plasticity of projections from brainstem auditory structures to the inferior colliculus (IC) was examined in albino rats to determine the effects of unilateral destruction of the IC during early development. The IC in the right hemisphere was destroyed by aspiration on postnatal day 3. Upon reaching adulthood, the rats were examined by retrograde tract tracing methods with fluoro-gold (FG) and [ 3H]-glycine to determine patterns of brainstem projections to the undamaged left IC. In our FG experiments, the results confirmed the presence of aberrant crossed projections from the right medial superior olive (MSO) to the undamaged left IC. Following injections of [ 3H]-glycine or FG into the undamaged left IC, however, no other aberrant projections were found in the superior olive, including those from the ipsilateral lateral superior olive (LSO) or the superior paraolivary nucleus (SPN). These results suggest that projections from the MSO to the IC may have the latent ability to create aberrant crossed projections during development. On the other hand, the neurons in LSO and SPN do not form aberrant projections following early unilateral IC lesions.

Cell death or survival: Molecular and connectional conditions for olivocochlear neurons after axotomy

We aimed to determine whether rat olivocochlear neurons survive axotomy inflicted through cochlear ablation, or if they degenerate. To estimate their intrinsic potential for axonal regeneration, we investigated the expression of the transcription factor c-Jun and the growth-associated protein-43 (GAP43). Axonal tracing studies based on application of Fast Blue into the cochlea and calcitonin gene-related peptide immunostaining revealed that many, but not all, lateral olivocochlear neurons in the ipsilateral lateral superior olive degenerated upon cochleotomy. A decrease of their number was noticed 2 weeks after the lesion, and 2 months postoperative the population was reduced to approximately one quarter (27–29%) of its original size. No further reduction took place at longer survival times up to 1 year. Most or all shell neurons and medial olivocochlear neurons survived axotomy. Following cochleotomy, 56–60% of the lateral olivocochlear neurons in the ipsilateral lateral superior olive were found to co-express c-Jun and GAP43. Only a small number of shell and medial olivocochlear neurons up-regulated c-Jun expression, and only a small number of shell neurons expressed GAP43. Up-regulation of c-Jun and GAP43 in lateral olivocochlear neurons upon axotomy suggests that they have an intrinsic potential to regenerate after axotomy, but cell counts based on the markers Fast Blue and calcitonin gene-related peptide indicate that this potential cannot be exploited and degeneration is induced instead. The survival of one quarter of the axotomized lateral olivocochlear neurons and of all, or almost all, shell and medial olivocochlear neurons appeared to depend on connections of these cells to other regions than the cochlea by means of axon collaterals, which remained intact after cochleotomy.

Electrical stimulation of the cochlear nerve in rats: analysis of c-Fos expression in auditory brainstem nuclei

We investigated functional activation of central auditory brainstem nuclei in response to direct electrical stimulation of the cochlear nerve using c-Fos immunoreactivity as a marker for functional mapping. The cochlear nerve was stimulated in the cerebellopontine angle of Lewis rats applying biphasic electrical pulses (120–250 μA, 5 Hz) for 30 min. In a control group, bilateral cochlectomy was performed in order to assess the basal expression of c-Fos in the auditory brainstem nuclei. The completeness of cochlear ablations and the response of auditory brainstem nuclei to electrical stimulation were electrophysiologically verified. C-Fos immunohistochemistry was performed using the free floating method. In anaesthetized animals with unilateral electrical stimulation of the cochlear nerve, increased expression of c-Fos was detected in the ipsilateral ventral cochlear nucleus (VCN), in the dorsal cochlear nucleus bilaterally (DCN), in the ipsilateral lateral superior olive (LSO) and in the contralateral inferior colliculus (IC). A bilateral slight increase of c-Fos expression in all subdivisions of the lateral lemniscus (LL) did not reach statistical significance. Contralateral inhibition of the nuclei of the trapezoid body (TB) was observed. Our data show that unilateral electrical stimulation of the cochlear nerve leads to increased expression of c-Fos in most auditory brainstem nuclei, similar to monaural auditory stimulation. They also confirm previous studies suggesting inhibitory connections between the cochlear nuclei. C-Fos immunoreactivity mapping is an efficient tool to detect functional changes following direct electrical stimulation of the cochlear nerve on the cellular level. This could be particularly helpful in studies of differential activation of the central auditory system by experimental cochlear and brainstem implants.

Axonal pathways to the lateral superior olive labeled with biotinylated dextran amine injections in the dorsal cochlear nucleus of rats.

The lateral superior olive (LSO) contains cells that are sensitive to intensity differences between the two ears, a feature used by the brain to localize sounds in space. This report describes a source of input to the LSO that complements bushy cell projections from the ventral cochlear nucleus (VCN). Injections of biotinylated dextran amine (BDA) into the dorsal cochlear nucleus (DCN) of the rat label axons and swellings in several brainstem structures, including the ipsilateral LSO. Labeling in the ipsilateral LSO was confined to a thin band that extended throughout the length of the structure such that it resembled an LSO isofrequency lamina. The source of this labeled pathway was not obvious, because DCN neurons do not project to the LSO, and VCN bushy cells were not filled by these injections. Filled neurons in several brainstem structures emerged as possible sources. Three observations suggest that most of the axonal labeling in the LSO derives from a single source. First, the number of labeled VCN planar multipolar cells and the amount of labeling in the LSO were consistent and robust across animals. In contrast, the number of labeled cells in most other structures was small and highly variable. Second, the locations of planar cells and filled axons in the LSO were related topographically to the position of the DCN injection site. Third, labeled terminal arborizations in the LSO arose from collaterals of axons in the trapezoid body (output tract of planar cells). We infer that planar multipolar cells, in addition to bushy cells, are a source of ascending input from the cochlear nucleus to the LSO.

The medial nucleus of the trapezoid body in the gerbil is more than a relay: comparison of pre- and postsynaptic activity.

The medial nucleus of the trapezoid body (MNTB) plays an important role in the processing of interaural intensity differences, a feature that is critical for the localization of sound sources. It is generally believed that the MNTB functions primarily as a passive relay in converting excitatory input originating from the contralateral cochlear nucleus (CN) into an inhibitory input to the ipsilateral lateral superior olive. However, studies showing that the MNTB itself is also the target of inhibitory input suggest that the MNTB may serve more than a sign-converting function. To examine the fidelity of signal transmission at the CN-MNTB synapse, presynaptic calyceal potentials ("prepotentials"), reflecting the excitatory input to the MNTB neuron, and postsynaptic action potentials were simultaneously monitored with the same electrode during in vivo extracellular recordings from the gerbil's MNTB. Presynaptic activity differed from postsynaptic activity in several respects: (1) Spontaneous and sound-evoked discharge rates were greater presynaptically than postsynaptically. (2) Frequency tuning was sharper postsynaptically than presynaptically. (3) Calyceal terminals and MNTB neurons both showed phasic-tonic response patterns to tonal stimulation, but the duration of the onset response and the level of the tonic component were reduced postsynaptically. (4) Phase-locking to sound frequencies up to 1 kHz was greater postsynaptically than presynaptically. (5) The rate-intensity characteristics of pre- and postsynaptic activities differed significantly from each other in half of the MNTB neurons. To test the hypothesis that acoustically evoked inhibition of MNTB neurons contributed to the relatively lower levels of postsynaptic discharge, two-tone stimulation was applied, wherein the response to one tone-burst, set at the neuron's characteristic frequency, can be reduced by addition of a second "inhibitory" tone. The inhibitory tone caused a much larger reduction in post- than in presynaptic activity, indicating an acoustically evoked inhibitory influence directly on MNTB units. These findings show that transmission at the CN-MNTB synapse does not occur in a fixed one-to-one manner and that the response of MNTB neurons reflects the integration of their excitatory and inhibitory inputs.

Model calculations of time dependent responses to binaural stimuli in the dorsal nucleus of the lateral lemniscus

In a previous paper (Reed and Blum, 1999), we examined the connectional hypotheses put forward by Markovitz and Pollak (1994) to explain the steady-state behavior of cells in the dorsal nucleus of the lateral lemniscus (DNLL). We found that the steady-state outputs of the four major binaural types of cells found in the DNLL (EI, EI/F, EE/I, and EE/FI) could be accounted for by known connectional patterns using only one or two cells per nucleus and quite simple hypotheses on cell behavior. In this study, we examine the time course of DNLL outputs in response to constant, ongoing, monaural or binaural sounds of various intensities. The model auditory nerve fibers ramp up linearly (usually in 2 ms) to full firing and the anteroventral cochlear nucleus cells have primary-like discharge patterns. Fixed time delays of 1 ms at each synapse are included; other time delays are employed when necessary to understand and reproduce specific features of the experimental data. We find that the connectional patterns utilized in our previous study can account for the rich variety of temporal response patterns found experimentally in the DNLL. Our main findings are: (1) all of the four major binaural types of cells can arise from modifications of the basic connectional pattern that produces EI cells; (2) both excitation and inhibition from the ipsilateral lateral superior olive (LSO) are required to understand DNLL responses; (3) pauser behavior can arise either from time delayed inhibition from a DNLL interneuron or by projection from the LSO; (4) two different mechanisms can account for the ipsilaterally evoked onset response; (5) to explain completely the temporal discharge pattern and binaural interactions of EE/FI cells, a projection from the contralateral DNLL via the commissure of Probst is necessary.

Ascending efferent projections of the superior olivary complex.

The superior olivary complex conveys information about binaural time and intensity to higher centers in the auditory pathway. This information is sent primarily to the subdivisions of the inferior colliculus and to the nuclei of the lateral lemniscus. Olivary projections are the predominant afferents to the central nucleus of the inferior colliculus. Electron microscopic observations of axonal endings in the central nucleus suggest that the ipsilateral medial superior olive and contralateral lateral superior olive make excitatory synapses. In contrast, the axons from the ipsilateral lateral superior olive to the central nucleus contain glycine and have a morphology consistent with inhibitory synapses. Little is known about the transmitter types used by olivary projections to the nuclei of the lateral lemniscus, but they are presumed to be similar to the collicular projections. Olivary ascending efferents are tonotopically organized and terminate in laminae in the inferior colliculus. They combine with other laminar afferents and postsynaptic neurons to create fibro-dendritic laminae in the colliculus. The key to the functional organization of the olivary efferents is the possible segregation of excitatory olivary efferents from each other in "synaptic domains" located on the laminae. This segregation may be the major determinant of response properties in the colliculus. Olivary efferents may converge with other non-olivary afferents on the same postsynaptic neurons in the colliculus. Inhibitory efferents from the lateral superior olive are essential in shaping the response properties of neurons in the colliculus. Olivary efferents to the nuclei of the lateral lemniscus are also key components of ascending pathways that inhibit neurons in the midbrain.

Auditory brainstem: Development and plasticity of GAP-43 mRNA expression in the rat

Expression of the growth and plasticity associated protein GAP-43 is closely related to synaptogenesis and synaptic remodeling in the developing as well as in the mature nervous system. We have studied the postnatal development of GAP-43 mRNA expression in the auditory brainstem and determined the time course of its reexpression following deafening through cochlear ablation using a digoxigenin-coupled mRNA probe. By the first postnatal day, GAP-43 mRNA was expressed at high levels in all auditory brainstem nuclei. But whereas GAP-43 mRNA is almost entirely lost in most of these nuclei in the adult animal, significant levels of this molecule are retained in the inferior colliculus and, most notably, in the lateral and medial superior olivary nucleus. As a consequence of unilateral cochleotomy, GAP-43 mRNA rose dramatically in some neurons of the ipsilateral lateral superior olive, whereas the hybridization signal decreased in others. Using double staining protocols, we found that those olivary neurons that increase their level of GAP-43 mRNA appear to be identical with the cells developing strong GAP-43 immunoreactivity after cochleotomy. By combining axonal tracing with in situ hybridization, we proved that at least some of the cells with increased levels of GAP-43 mRNA and protein are the cells of origin of olivocochlear projections. A substantial decrease of the level of GAP-43 mRNA took place in the inferior colliculus contralateral to the lesioned cochlea. Our results led us to suggest that neurons in the superior olivary complex may play a crucial role in orchestrating auditory brainstem plasticity.

Projection Neurons in the Superior Olivary Complex of the Rat Auditory Brainstem: A Double Retrograde Tracing Study

The superior olivary complex (SOC), a group of interrelated brainstem nuclei, sends efferents to a variety of neuronal structures including the cochlea and the inferior colliculus (IC). In the present study conducted in rats, we sought to investigate whether single SOC efferent neurons project to both cochlea and IC. These neurons were identified by retrograde axonal transport of the neuronal tracers fluoro-gold upon application to the cochlea and cholera toxin B subunit injected into the central nucleus of the IC. Projections to the cochlea were found to stem predominantly from the ipsilateral lateral superior olive (LSO) and medial superior olive (MSO) as well as from the bilateral superior paraolivary nucleus (SPO), dorsal periolivary groups (DPO) and the medial nucleus of the trapezoid body (MNTB). Neurons innervating the IC were seen in the bilateral LSO and DPO, in the SPO predominantly ipsilateral, as well as in the ipsilateral MSO and MNTB. We further observed that some neurons in the ipsilateral LSO, and a considerable part of those of the SPO were double-labeled. However, cells projecting to either IC or cochlea were much more numerous than double-labeled neurons.

Afferent regulation of glycine receptor distribution in the gerbil LSO.

Synaptic activity plays an important role in many aspects ofneuronal development, particularly the expression of proteins. In this study, the influence of inhibitory and excitatory afferents on the development of glycine receptor density in the lateral superior olive (LSO) of Mongolian gerbils was investigated. Afferent activity was manipulated by removing one or both cochleas at postnatal day 7, prior to the onset of sound-evoked responses. Due to the anatomy of the LSO, these manipulations result in either excitatory denervation, inhibitory denervation, or both. The density of glycine receptors in the LSO was determined at 21 days postnatal. Glycine receptors were either labeled with tritiated strychnine (3H-SN) or with an antibody directed against gephyrin, a protein closely associated with the receptor complex. Antibody binding was used to quantify the differential glycine receptor density between the medial limb (high frequency area) and the lateral limb (low frequency area) of the LSO. 3H-SN was used to quantify the amount of glycine receptors in each part of the LSO in control and experimental animals. In addition, changes in neuron density and neuron cross-sectional area were quantified following cochlear ablations. In control animals, the amount of glycine receptors is about 2- to 3-fold higher in the high-frequency than in the low-frequency region. In bilaterally ablated animals, the same density of glycine receptors was measured in the high- and low-frequency region. Unilateral ablations had no significant effect on glycine receptor distribution, either ipsi- or contralateral to the ablation. The neuron cross-sectional area decreased about 30% in the ipsilateral LSO of unilaterally ablated animals and in bilaterally ablated animals. However, alterations of soma density and cross-sectional area were similar in the high- and low-frequency projection region. These results suggest that the distribution of glycine receptors is only changed when excitatory and inhibitory afferents have been denervated.

Deafferentation weakens excitatory synapses in the developing central auditory system.

Decreased excitatory synaptic activity during development often leads to pre- and postsynaptic atrophy, as assessed anatomically. The present study considers the effect of decreased excitatory transmission on the maturation of synaptic strength. Towards this end, cochlear nucleus neurons, which project to the ipsilateral lateral superior olive (LSO), were denervated in gerbils at postnatal day 7, before the onset of hearing. This manipulation was intended to disrupt spontaneous glutamatergic transmission in the LSO while sparing the glycinergic afferents from the medial nucleus of the trapezoid body (MNTB). Afferent-evoked synaptic activity was assessed 1-6 days after ablation in a brain slice preparation using whole-cell current- and voltage-clamp recordings. In control animals, ipsilaterally evoked excitatory postsynaptic potentials (EPSPs) were present in 91% of neurons tested, but were observed in only 60% of neurons following cochlea removal. The maximum EPSP amplitude was significantly smaller in manipulated neurons compared with controls, and this was accompanied by a higher incidence of ipsilaterally evoked inhibitory postsynaptic potentials (IPSPs). To study the efficacy of excitatory synapses in greater detail, voltage-clamp recordings were made in the presence of strychnine and AP-5 [D(O)-2-amino-5-phosphonopentanoic acid]. The minimum excitatory postsynaptic current (EPSC) amplitude, presumed to reflect the efficacy of a single glutamatergic afferent, was approximately 40% smaller in manipulated neurons. In contrast, MNTB-evoked IPSPs were similar in neurons from control and ablated animals. However, manipulated neurons often exhibited a rebound depolarization after a hyperpolarizing current pulse or an afferent-evoked IPSP. In 70% of manipulated neurons, synaptically evoked rebound depolarizations were reduced, but not eliminated, by glutamate receptor antagonists. The glycine receptor antagonist strychnine did eliminate the IPSP-associated depolarization in these neurons. Collectively, these results suggest that functional denervation of excitatory afferents decreases their synaptic efficacy as result of both cell loss as well as decreased strength of individual surviving synapses.

Simultaneous anterograde labeling of axonal layers from lateral superior olive and dorsal cochlear nucleus in the inferior colliculus of cat

The laminar organization of the central nucleus of inferior colliculus includes layers of axons that may be important in shaping the responses of neurons. Depending on their source, some layered axons are afferents that are superimposed and terminate on the same postsynaptic neurons, while other layered afferents, such as those from the ipsilateral and contralateral lateral superior olive, terminate side-by-side. The specific pattern of convergence may dictate which populations of axons are presynaptic to layered disc-shaped neurons in the central nucleus. We compared the distribution of afferent axons from the dorsal cochlear nucleus and the lateral superior olive to the contralateral inferior colliculus in the cat. Injection sites in cochlear nucleus and superior olive were physiologically characterized by extracellular recordings of single and multiple units in response to monaural and binaural acoustic stimulation. Two separate injections were made in each case, and both injection sites contained units with overlapping best frequencies. Biotinylated dextran, fluorescent dextran, 3H-leucine, and wheat germ agglutinin conjugated to horseradish peroxidase were used as anterograde tracers. The present results show that layered axons from the dorsal cochlear nucleus and lateral superior olive are superimposed in part of the contralateral central nucleus. Both projections were arranged in rostro-caudally oriented axonal layers that converged in the ventral part of the central nucleus. However, in the dorsal part of the central nucleus, the same layer of axons from the dorsal cochlear nucleus did not terminate with afferents from the lateral superior olive. Within the overlapping layers in the ventral central nucleus, the overlap of axons from the dorsal cochlear nucleus and the lateral superior olive was uniform except for small patches that were usually smaller than the dendritic fields of disc-shaped neurons. These data suggest that the layers may create specific functional zones in the central nucleus of the inferior colliculus. One zone may contain neurons with binaural responses that combine the properties of the inputs from the contralateral lateral superior olive and the dorsal cochlear nucleus. A second zone may contain inputs from the cochlear nucleus but lack those of the lateral superior olive.

Plasticity of the auditory brainstem: effects of cochlear ablation on GAP-43 immunoreactivity in the rat.

In the adult brain, expression of the growth associated protein GAP-43 may serve as an indicator of synaptic remodeling. We have studied localization and time course of the re-expression of GAP-43 following deafening through cochlear ablation. As a consequence of unilateral cochlear lesioning, a substantial increase in the expression of GAP-43 was observed in the neuropil of all subnuclei of the ipsilateral cochlear nuclear complex. This expression of GAP-43 occurred in well-defined fibers and boutons. In the ventral cochlear nuclei, boutons immunoreactive for GAP-43 were often localized on cell bodies. However, they were found only on selected subpopulations of cochlear nucleus neurons, i.e., on cell bodies containing glutamate or calretinin immunoreactivity, but apparently not on GABAergic neurons. Olivocochlear neurons must have been axotomized by the operation. Following cochlear ablation, a dramatic re-expression of GAP-43 occurred in cell bodies of the ipsilateral lateral superior olive but not in the ventral nucleus of the trapezoid body. Position and number of these cells suggested that most, if not all, of them serve the lateral olivocochlear bundle. However, although axon collaterals are given off by certain types of olivocochlear neurons, a direct involvement of the immunoreactive cell bodies in the emergence of GAP-43 in the cochlear nucleus is not obvious. A transient rise of GAP-43 immunoreactivity that could not be attributed to axotomized neurons was observed in the contralateral dorsal cochlear nucleus and in the ipsilateral inferior colliculus. Given the functional significance attributed to GAP-43, we conclude that the sudden loss of spiral ganglion cells leads to a reactive synaptogenesis in complex patterns across several auditory brainstem nuclei.

Axonal projections from the lateral and medial superior olive to the inferior colliculus of the cat: a study using electron microscopic autoradiography.

The superior olivary complex is the first site in the central auditory system where binaural interactions occur. The output of these nuclei is direct to the central nucleus of the inferior colliculus, where binaural inputs synapse with monaural afferents such as those from the cochlear nuclei. Despite the importance of the olivary pathways for binaural information processing, little is known about their synaptic organization in the colliculus. The present study investigates the structure of the projections from the lateral and medial superior olivary nuclei to the inferior colliculus at the electron microscopic level. Stereotaxic placement and electrophysiological responses to binaural sounds were used to locate the superior olive. Anterograde axonal transport of 3H-leucine was combined with light and electron microscopic autoradiography to reveal the location and morphology of the olivary axonal endings. The results show that the superior olivary complex contributes different patterns of synaptic input to the central nucleus of the inferior colliculus. Each projection from the superior olivary complex to the colliculus differs in the number and combinations of endings. Axonal endings from the ipsilateral medial superior olive were exclusively the round (R) type that contain round synaptic vesicles and make asymmetrical synaptic junctions. This morphology is usually associated with excitatory synapses and neurotransmitters such as glutamate. Endings from medial superior olive terminate densely in the central nucleus. The projection from the contralateral lateral superior olive also terminates primarily as R endings. This projection also includes small numbers of pleomorphic (PL) endings that contain pleomorphic synaptic vesicles and usually make symmetrical synaptic junctions. The PL morphology is associated with inhibitory synapses and transmitters such as gamma-aminobutyric acid and glycine. All endings from the contralateral lateral superior olive terminate much less densely than endings from the medial olive. In contrast, the projection from the ipsilateral lateral superior olive contributes both R and PL endings in roughly equal proportions. These ipsilateral afferents are heterogeneous in density and can terminate in lower or higher concentrations than endings from the contralateral side. These data show that the superior olive is a major contributor to the synaptic organization of the central nucleus of the inferior colliculus. The ipsilateral projections of the medial and lateral superior olive may produce higher concentrations of R endings than other inputs to the central nucleus. Such endings may participate in excitatory synapses. The highest concentrations of PL endings come from the ipsilateral lateral superior olive.(ABSTRACT TRUNCATED AT 400 WORDS)

Lateral superior olive projections to the inferior colliculus in normal and unilaterally deafened ferrets

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.

Development of ventral cochlear nucleus projections to the superior olivary complex in gerbil

The postnatal development of the projection from the ventral cochlear nucleus to the principal nuclei in the superior olivary complex in gerbil (Meriones unguiculatus) was studied in an age-graded series of pups ranging from 0 to 18 days old. Small crystals of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) were inserted into the ventral cochlear nucleus of aldehyde-fixed brains, and the labeled projections were examined with epifluorescence microscopy. Selected sections were photooxidized in a solution of diaminobenzidine and subsequently processed for electron microscopy to examine the development of labeled synapses in the target nuclei. Horseradish peroxidase was injected into the ventral cochlear nucleus of adult gerbils to assess the form and persistence of projections observed in the neonatal animals. In addition, electrophysiological responses to acoustic stimuli of single units in the adult auditory brainstem were analyzed to confirm the functionality of the novel projection from the ventral cochlear nucleus to the contralateral lateral superior olive. By the day of birth (P0), developing axons from the ventral cochlear nucleus have already established highly ordered pathways to the three primary nuclei of the superior olivary complex: the ipsilateral lateral superior olive, the contralateral medial nucleus of the trapezoid body, and at the lateral and medial dendrites of the ipsilateral and contralateral medial superior olive, respectively. Developing axons from the ventral cochlear nucleus that innervated the contralateral medial nucleus of the trapezoid body lacked the terminal morphology characteristic of the calyx of Held, but began to adopt a more characteristic form on P5. The mature calyx appeared around P14-16. Exuberant developmental projections to topographically inappropriate areas of the superior olivary complex were not observed at the postnatal ages studied. In addition to the projections of the ventral cochlear nucleus to the superior olivary complex described in other species, we observed the development and maintenance of a major direct projection from the ventral cochlear nucleus to the contralateral lateral superior olive. On P0, ventral cochlear nucleus axons decussate in the dorsal trapezoid body, form a plexus at the dorsal edge of the contralateral medial superior olive, and enter the ventrolateral limb of the contralateral lateral superior olive. Over the next 2 weeks, fascicles of fibers form on the hilar and ventral aspects of the ventrolateral limb. Fibers arising from these fascicles form converging, but nonoverlapping, arborizations within the ventrolateral limb at right angles to the curvature of the nucleus. The medial region was devoid of labeled axons.(ABSTRACT TRUNCATED AT 400 WORDS)