Cochlear and middle ear effects on metabolism in the central auditory pathway during silence: A 2-deoxyglucose study

The [¹⁴C]2-deoxy-d-glucose (2-DG) autoradiographic technique was used to investigate metabolic activity in the central auditory pathways during silence. Relative 2-DG uptake was assessed in silence for three groups of Mongolian gerbils: control animals; those with unilateral cochlear ablations, and those with unilateral conductive hearing losses. Control subjects showed no differences between the two sides of their central auditory pathways. Subjects with unilateral cochlear ablations showed markedly lower 2-DG uptake in the major afferent projection pathway from the ablated cochlea compared with 2-DG uptake in contralateral structures. That is, relative 2-DG uptake was significantly lower ipsilateral to the ablation in the anteroventral and dorsal cochlear nuclei, and contralateral to the ablation in the ventral nucleus of the lateral lemniscus, the dorsal nucleus of the lateral lemniscus, and the inferior colliculus. No effect of ablation was seen in the superior olivary complex, the medial geniculate nucleus or the auditory cortex. Subjects with a unilateral conductive hearing loss, unexpectedly, showed significantly higher 2-DG incorporation in the major afferent projection from the impaired side. That is, relative 2-DG uptake was higher in the anteroventral cochlear nucleus, the dorsal cochlear nucleus and the lateral superior olivary nucleus ipsilateral to the hearing loss, and in the dorsal nucleus of the lateral lemniscus contralateral to the hearing loss. These increases in 2-DG uptake following conductive hearing loss represent a mechanism which may account for clinical hearing disorders such as tinnitus. It is concluded that, even under conditions of silence, the intact cochlea and middle ear conductive apparatus significantly influence metabolic activity in the central auditory pathway up through the level of the inferior colliculus.     

Plasticity in the development of afferent patterns in the inferior colliculus of the rat after unilateral cochlear ablation.

The central nucleus of the inferior colliculus (IC) is the site of convergence for nearly all ascending monaural and binaural projections. Several of these inputs, including inhibitory connections from the dorsal nucleus of the lateral lemniscus (DNLL), are highly ordered and organized into series of afferent bands or patches. Although inputs to the IC from the contralateral DNLL are present in the rat by birth [postnatal day 0 (P0)], the earliest indications of band formation are not evident until P4. Subsequently, the initially diffuse projection segregates into a pattern of bands and interband spaces, and by P12 adult-like, afferent-dense patches are established (Gabriele et al., 2000). To determine the role of the auditory periphery in the development of bands and patches before the onset of hearing (P12/P13), unilateral cochlear ablations were performed at P2 (before any evidence of banding). Rat pups were reared to P12, at which time glass pins coated with 1, 1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate were placed in fixed tissue in the commissure of Probst where DNLL fibers cross the midline. The results indicate that a unilateral cochlear ablation disrupts the normal development of afferent patches in the IC. Although the crossed DNLL projections labeled via commissural dye placement always mirrored each other in P12 controls, ablation cases exhibited a consistent, bilateral asymmetry in pattern formation and relative density of the labeled projections. Possible developmental mechanisms likely to be involved in the establishment of afferent bands and patches before the onset of hearing are discussed.     

Responses from two ifring patterns in inferior colliculus neurons to stimulation of the lateral lemniscus dorsal nucleus

Theγ-aminobutyric acid neurons (GABAergic neurons) in the inferior colliculus are classiifed into various patterns based on their intrin-sic electrical properties to a constant current injection. Although this classiifcation is associated with physiological function, the exact role for neurons with various ifring patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neuronsin vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the whole-cell patch clamp technique. Seven inferior colliculus neurons were tested and were classiifed into two ifring patterns: sustained-regular (n = 4) and sustained-adapting ifring patterns (n = 3). The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting ifring pattern were suppressed after stimulation, but recovered to normal levels following application of theγ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting ifring patterns. Additionally, GABAergic projections from the dorsal nu-cleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various ifring patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deifciencies.     

The effect of bilateral deafness on excitatory and inhibitory synaptic strength in the inferior colliculus

The consequences of deafness on the central auditory nervous system have been examined at many levels, from molecular to functional. However, there has never been a direct and selective measurement of excitatory synaptic function following total hearing loss. In the present study, gerbils were deafened at postnatal day 9, an age at which there is no deafferentation-induced cell death of ventral cochlear nucleus neurons. One to five days after bilateral cochlear ablation, the amplitude of evoked excitatory postsynaptic currents (EPSC) was measured with whole-cell voltage-clamp recordings in an inferior colliculus (IC) brain slice preparation in response to electrical stimulation of the ipsilateral lateral lemniscus (LL) or the commissure of the inferior colliculus (CIC). Deafness resulted in larger LL- and CIC-evoked EPSC amplitudes and durations. This result was observed at a depolarized holding potential. In addition, deafness caused a decrease in excitatory neurotransmitter release at the LL pathway, as assessed with a paired-pulse stimulation protocol. In contrast to its effect on excitatory synapses, bilateral cochlear ablation reduced inhibitory synaptic strength in IC neurons. The effects included a postsynaptic decrease in IPSC conductance, a 25-mV depolarization in the IPSC equilibrium potential and a decrease of neurotransmitter release. Thus normal innervation differentially affects excitatory and inhibitory synaptic strength in IC neurons, and these changes may contribute to alterations in auditory coding properties following sensory deprivation.     

Central acoustic tract in an echolocating bat: an extralemniscal auditory pathway to the thalamus

To determine the sources and targets of auditory pathways that bypass the inferior colliculus in the mustache bat, we injected WGA-HRP in the medial geniculate body and related auditory nuclei of the thalamus as well as in the lower brainstem. We used electrophysiological methods to verify that the injection electrode was in an area responsive to sound. The only thalamic injections that produced retrograde transport to cells in auditory nuclei caudal to the inferior colliculus were those that included the suprageniculate nucleus. These injections labeled a group of large multipolar cells lying between the ventral nucleus of the lateral lemniscus and the superior olivary complex. Neurons in this cell group have also been shown to project to the deep layers of the superior colliculus in the mustache bat. The pathway revealed by these studies is almost identical to the "central acoustic tract" in which fibers course medial to the lateral lemniscus and bypass the inferior colliculus to reach the deep superior colliculus and the suprageniculate nucleus.     

Time course of embryonic midbrain and thalamic auditory connection development in mice as revealed by carbocyanine dye tracing

Central auditory connections develop in mice before the onset of hearing, around postnatal day 7. Two previous studies have investigated the development of auditory nuclei projections and lateral lemniscal nuclear projections in embryonic rats, respectively. Here, we provide detail for the first time of the initiation and progression of projections from the inferior colliculus (IC) to the medial geniculate body (MGB) and from the MGB to the auditory cortex (AC). Overall, the developmental progression of projections follows that of terminal mitoses in various nuclei, suggesting the consistent use of a developmental timetable at a given nucleus, independent of that of other nuclei. Our data further suggest that neurons project specifically and reciprocally from the MGB to the AC as early as embryonic day 14.5. These projections develop approximately a day before the reciprocal connections between the MGB and IC and before development of projections from the auditory nuclei to the IC. The development of IC projections is prolonged and progresses from rostral to caudal areas. Brainstem nuclear projections to the IC arrive first from the lateral lemniscus nuclei then the superior olive and finally the cochlear nuclei. Overall, the auditory connection development strongly suggests that most of the overall specificity of nuclear connections is set up at least 2 weeks before the onset of sound-mediated cochlea responses in mice and, thus, is likely governed predominantly by molecular genetic clues.     

Organization of the inferior colliculus of the gerbil (Meriones unguiculatus): differences in distribution of projections from the cochlear nuclei and the superior olivary complex

The inferior colliculus (IC) receives its major ascending input from the cochlear nuclei, the superior olivary complex, and the nuclei of the lateral lemniscus. To understand better the terminal distribution of the inputs from these sources relative to one another, we made focal injections of a retrograde tracer, biotinylated dextran amine, in different parts of the IC in 74 gerbils (Meriones unguiculatus). The cases could be divided into three groups based on counts of labeled cells in brainstem auditory nuclei. Group 1 cases had labeled cells in both the cochlear nuclei and the lateral and medial superior olivary nuclei. Group 2 cases had labeled cells in the cochlear nuclei but few or none in the lateral and medial superior olivary nuclei. Both groups had labeled cells in the nuclei of the lateral lemniscus and the superior paraolivary nucleus. Group 3 cases had few labeled cells in any of the ascending auditory pathways. The group to which a case belonged was strongly related to the location of the injection site in the IC. The injection sites for both group 1 and group 2 were located in the central nucleus, but those for group 1 tended to be located laterally relative to those for group 2, which were located more medially and caudally. The injection sites for group 3 cases lay outside the central nucleus of the IC. The two regions of the central nucleus of the IC, distinguished on the basis of connectivity, are likely to subserve different functions.     

EM autoradiographic study of the projections from the dorsal nucleus of the lateral lemniscus: a possible source of inhibitory inputs to the inferior colliculus

The fine structure of the projection from the dorsal nucleus of the lateral lemniscus (DNLL) to the inferior colliculus is examined in the cat. Anterograde axonal transport of 3H-leucine and EM autoradiographic techniques are used to label axonal endings from DNLL. The primary finding is that axonal endings from DNLL contain pleomorphic synaptic vesicles and make symmetrical synaptic contacts. This morphology is associated with inhibitory synapses. The projection from DNLL is the source of approximately one-third of the axonal endings with pleomorphic vesicles in the central nucleus of the inferior colliculus. In the contralateral central nucleus, only labeled endings with pleomorphic vesicles are found. By comparison, on the ipsilateral side, both endings with pleomorphic vesicles and, to a lesser degree, endings with round vesicles are labeled. Endings from DNLL are more numerous per unit area on the contralateral side. About half of the labeled axonal endings from DNLL terminate upon small dendrites, and another third terminate upon more proximal dendrites and several types of cell bodies. Many axonal endings form multiple synaptic contacts, sometimes on more than one postsynaptic structure. Sites of termination for axonal endings include dendritic spines and branch points of dendrites. These data support the hypothesis that the DNLL pathway to the inferior colliculus may have an inhibitory function. Previous studies show that DNLL neurons exhibit immunoreactivity to GAD and GABA antibodies. The crossed projection of DNLL to the inferior colliculus forms tonotopically organized bands that terminate as endings with pleomorphic vesicles. These endings may supply GABAergic inputs to the inferior colliculus. Thus, bands from DNLL could provide inhibitory inputs and overlap with bands from other sources that provide excitatory inputs. Overlapping bands may form unique synaptic domains in the inferior colliculus. The uncrossed projections from DNLL may provide the inferior colliculus with a more diffusely organized projection that could include excitatory and inhibitory inputs. Since the DNLL on one side may inhibit the opposite DNLL and the inferior colliculus, the DNLL pathway may regulate ascending inhibition to the midbrain. Presumed inhibitory inputs from DNLL to the inferior colliculus could be involved in binaural information processing and contralateral dominance.     

Acoustic chiasm. IV: Eight midbrain decussations of the auditory system in the cat.

Conventional retrograde and orthograde axonal transport tract-tracing techniques were used in cats to explore the auditory decussations and commissures in the upper pons and midbrain. In all, 8 decussations differing either in origin or in contralateral termination were found. Three of the 8 decussations (from the dorsal nucleus of the lateral lemniscus to the contralateral dorsal nucleus of the lateral lemniscus, from the dorsal nucleus of the lateral lemniscus to the contralateral inferior colliculus, from the sagulum to the contralateral sagulum) reach their targets via the commissure of Probst. The remaining 5 decussations (from the inferior colliculus to the contralateral inferior colliculus or medial geniculate, from the intermediate nucleus of the lateral lemniscus to the contralateral medial geniculate, from the sagulum to the contralateral inferior colliculus or medial geniculate) reach their targets via the commissure of the inferior colliculus. The results also suggest that the commissure of Probst is not a general avenue for decussating auditory fibers of the lateral lemniscus but is instead a specific avenue only for fibers from the dorsal nucleus of the lateral lemniscus and sagulum. The results also show that, in the cat at least, the dorsal nucleus of the lateral lemniscus does not project beyond the inferior colliculus to either the superior colliculus or medial geniculate--the cells previously reported as doing so are probably those of the immediate neighbors of the dorsal nucleus, the intermediate nucleus of the lateral lemniscus and sagulum.     

The speeding of EPSC kinetics during maturation of a central synapse

Several factors contribute to the shape of excitatory postsynaptic currents (EPSCs) in CNS neurons, among them the kinetics of presynaptic release, transmitter clearance, and the properties and distribution of postsynaptic receptors. The decays of AMPA receptor-mediated EPSCs at rat cerebellar mossy fibre-granule cell (MF-gc) synapses follow a bi-exponential time-course. The fast component dominates the decay, accounting for 84-94% of the peak amplitude. Here we show that both components of decay, and also the risetimes, became faster during postnatal maturation. At adult, but not immature, synapses, the risetimes and decays of evoked multiquantal EPSCs were similar to those of monoquantal miniature (m)EPSCs. The faster risetimes at mature synapses reflected increased synchrony of multivesicular release, whereas the faster decays appeared to reflect changes in the properties of postsynaptic receptors. Inhibition of glutamate uptake was without effect on evoked EPSCs at both ages. Furthermore, after slowing receptor desensitization with cyclothiazide, the EPSCs at mature synapses decayed as slowly as EPSCs at immature synapses, suggesting that faster glutamate clearance does not account for the developmental speeding of EPSC decay. Our results support previous conclusions that glutamate clearance and receptor deactivation are important determinants of the fast decay component at immature synapses. Desensitization becomes increasingly important during development and plays a major role in shaping EPSC decay at mature synapses.     

The subcortical auditory structures in the Mongolian gerbil: II. Frequency‐related topography of the connections with cortical field AI

We investigated the frequency‐related topography of connections of the primary auditory cortical field (AI) in the Mongolian gerbil with subcortical structures of the auditory system by means of the axonal transport of two bidirectional tracers, which were simultaneously injected into regions of AI with different best frequencies (BFs). We found topographic, most likely frequency‐matched (tonotopic) connections as well as non‐topographic (non‐tonotopic) connections. AI projects in a tonotopic way to the ipsilateral ventral (MGv) and dorsal divisions (MGd) of the medial geniculate body (MGB), the reticular thalamic nucleus and dorsal nucleus of the lateral lemniscus, and the ipsi‐ and contralateral dorsal cortex of the inferior colliculus (IC) and central nucleus of the IC. AI receives tonotopic inputs from MGv and MGd. Projections from different BF regions of AI terminate in a non‐tonotopic way in the ipsilateral medial division of the MGB (MGm), the suprageniculate thalamic nucleus (SG) and brachium of the IC (bic), and the ipsi‐ and contralateral external cortex and pericollicular areas of the IC. The anterograde labeling in the intermediate and ventral nucleus of the lateral lemniscus, parts of the superior olivary complex, and divisions of the cochlear nucleus was generally sparse; thus a clear topographic arrangement of the labeled axons could not be ruled out. AI receives non‐tonotopic inputs from the ipsilateral MGm, SG, and bic. In conclusion, the tonotopic and non‐tonotopic corticofugal connections of AI can potentially serve for both conservation and integration of frequency‐specific information in the respective target structures. J. Comp. Neurol. 521:2772–2797, 2013. © 2013 Wiley Periodicals, Inc.     

Nucleus sagulum: projections of a lateral tegmental area to the inferior colliculus in the cat

The nucleus sagulum, an area of the midbrain tegmentum, has been considered a component of a lateral tegmental system within the ascending auditory pathway to the thalamus. In this study, connections of the nucleus sagulum within the midbrain were investigated in adult cats. Tracing methods using anterograde and retrograde axonal transport of markers were employed. The nucleus sagulum was identified as a region of principally small neurons (261 +/- 79 micron2) at the margin of the midbrain and neighboring the nuclei of the lateral lemniscus. Injections of tritiated leucine in the nucleus sagulum labeled axons that ended in dense patches within the superficial layers of the caudal portion of the dorsal cortex of the inferior colliculus on the ipsilateral side. Retrograde experiments confirmed this connection. Other axonal projections labeled in the anterograde studies included fibers ending in the dorsomedial nucleus, the superficial layers of the dorsal cortex, and the rostral nucleus of the inferior colliculus with some bilateral distribution. Outside of the inferior colliculus, sagulum injections labeled other axons ending in the ventral intercollicular tegmentum on both sides and in a dorsal and rostral region of the contralateral nucleus sagulum that appeared contiguous with the dorsal nucleus of the lateral lemniscus. The latter region included a population of larger neurons (340-540 micron2) and had different connections with the inferior colliculus. The distribution of axonal labeling after injections in the nucleus sagulum was contrasted with the distribution of projections from several neighboring areas of the lateral tegmentum, including the dorsal nucleus of the lateral lemniscus. None of these areas exhibited connections with the superficial layers of the caudal cortex of the inferior colliculus, which was the major target in the inferior colliculus of the nucleus sagulum. Thus, the results indicated that the nucleus sagulum is distinguished from adjacent regions of the lateral tegmentum by its connectivity. Its association with midbrain auditory pathways is supported by these connections as well as ascending ones to the auditory thalamus.     

Auditory brainstem of the ferret: sources of projections to the inferior colliculus

The organization of the auditory brainstem in adult, darkly pigmented ferrets was studied by using the retrograde transport of the lectin wheat germ agglutinin-horseradish peroxidase injected into one inferior colliculus. Retrogradely labelled neurons were found bilaterally in every nucleus of the auditory brainstem. The greatest number of labelled neurons was found in the cochlear nuclei contralateral to the injection site, the ipsilateral medial superior olivary nucleus, both lateral superior olivary nuclei, the ipsilateral ventral nucleus of the lateral lemniscus, both dorsal nuclei of the lateral lemniscus, and the contralateral inferior colliculus. Quantitative assessment of the projections from the cochlear nuclei showed that the number of contralaterally projecting neurons exceeded the number of ipsilaterally projecting neurons by about 50 to one. This ratio remained relatively stable over a wide range of volumes of injected lectin, whereas the absolute number of labelled neurons on each side varied by at least twofold for a constant volume of lectin. These results provide basic data on the ferret auditory system and demonstrate quantitatively some properties of the projections between the cochlear nucleus and the inferior colliculus.     

Auditory pathways to the cortex in Tupaia glis

The auditory system of the tree shrew, Tupaia glis, was investigated by identifying axonal degeneration after lesions of the lateral lemniscus, the inferior colliculus, the medial geniculate nucleus and the auditory cortex. The results show that the lateral lemniscus projects to the central nucleus of the inferior colliculus which in turn projects principally to the ventral division of the medial geniculate nucleus but to a lesser extent to the magnocellular division of the medial geniculate nucleus. The final step in the pathway to the cortex is achieved by a projection from the ventral division to the fourth layer of auditory koniocortex. There appear to be several auditory pathways parallel to this primary path. The lateral lemniscus projects to the dorsal division of the medial geniculate nucleus; the deeper layers of the superior colliculus project to the posterior nucleus; and both the dorsal division and the posterior nucleus project to the belt caudal to auditory koniocortex. The caudal division of the medial geniculate nucleus may constitute a relay in still another path from the pericentral division of the inferior colliculus. Finally, the magnocellular division also appears to be distinct insofar as its cortical projections are confined chiefly to the deeper layers. A comparison between the tree shrew and the cat reveals a similar organization in the two species. In the cat the starting point for understanding the organization of the several auditory pathways is the distinction between a core cortical zone which corresponds to koniocortex and to AI and a peripheral belt. The core receives essential projections from the ventral division; the belt receives sustaining projections from the cell groups which surround the ventral division. It is reasonable to hypothesize that this difference between the core and the belt is characteristic of all mammals.     

Connections of the dorsal nucleus of the lateral lemniscus: An inhibitory parallel pathway in the ascending auditory system?

This study examines the dorsal nucleus of the lateral lemniscus (DNLL) and its afferent and efferent connections. In Nissl-stained material, DNLL has three parts: dorsal, ventral, and lateral. Although each part contains neurons with similar Nissl patterns, the subdivisions may be distinguished by the size, shape, and orientation of the cells. The lateral DNLL contains a mixture of DNLL neurons and cells from the sagulum. Afferent connections to DNLL were investigated with anterograde axonal transport techniques. Bilateral inputs to DNLL arise from the anteroventral cochlear nucleus and lateral superior olive, while unilateral inputs are provided by the ipsilateral medial superior olive and the contralateral DNLL. The inputs appear to have a tonotopic organization. Afferent fibers to DNLL form horizontal bands that are continuous both mediolaterally and rostrocaudally. All parts of DNLL do not share the same inputs, and a medial-to-lateral gradient in the labeling of some pathways is evident. To study the efferent connections of DNLL, both retrograde and anterograde axonal transport techniques were used. The DNLL projects to the inferior colliculus and the contralateral DNLL. The topography of these projections suggests that areas of similar tonotopic organization are connected. In the inferior colliculus, the projection is heaviest to the central nucleus and extends to the adjacent dorsal and caudal cortex, the rostral pole nucleus, and the ventrolateral nucleus. Axons from DNLL terminate along the fibrodendritic laminae of the central nucleus as bands that are prominent on the contralateral side, whereas those on the ipsilateral colliculus are more diffuse. The afferent and efferent connections of DNLL constitute a multisynaptic pathway, parallel to the other ascending pathways to the inferior colliculus. The other ascending pathways include the direct pathways from the cochlear nucleus to the inferior colliculus and the indirect pathways via the superior olivary complex. Ascending pathways are discussed as to their relationship to the subdivisions of the inferior colliculus, the laterality of their projections, and their banding patterns in the central nucleus. In contrast to the excitatory pathways to the inferior colliculus, the neurons in DNLL may use GABA as a neurotransmitter. Axons from the DNLL terminate in the inferior colliculus as bands that could have a unique inhibitory function. Thus, the multisynaptic, DNLL pathway may provide feed-forward inhibitory inputs to the inferior colliculus, bilaterally, and to the contralateral DNLL.     

Convergence of lemniscal and local excitatory inputs on large GABAergic tectothalamic neurons

Large GABAergic (LG) neurons form a distinct cell type in the inferior colliculus (IC), identified by the presence of dense VGLUT2‐containing axosomatic terminals. Although some of the axosomatic terminals originate from local and commissural IC neurons, it has been unclear whether LG neurons also receive axosomatic inputs from the lower auditory brainstem nuclei, i.e., cochlear nuclei (CN), superior olivary complex (SOC), and nuclei of the lateral lemniscus (NLL). In this study we injected recombinant viral tracers that force infected cells to express GFP in a Golgi‐like manner into the lower auditory brainstem nuclei to determine whether these nuclei directly innervate LG cell somata. Labeled axons from CN, SOC, and NLL terminated as excitatory axosomatic endings, identified by colabeling of GFP and VGLUT2, on single LG neurons in the IC. Each excitatory axon made only a few axosomatic contacts on each LG neuron. Inputs to a single LG cell are unlikely to be from a single brainstem nucleus, since lesions of individual nuclei failed to eliminate most VGLUT2‐positive terminals on the LG neurons. The estimated number of inputs on a single LG cell body was almost proportional to the surface area of the cell body. Double injections of different viruses into IC and a brainstem nucleus showed that LG neurons received inputs from both. These results demonstrated that both ascending and intrinsic sources converge on the LG somata to control inhibitory tectothalamic projections. J. Comp. Neurol. 523:2277–2296, 2015. © 2015 Wiley Periodicals, Inc.     

Circuitry underlying spectrotemporal integration in the auditory midbrain

Combination sensitivity in central auditory neurons is a form of spectrotemporal integration in which excitatory responses to sounds at one frequency are facilitated by sounds within a distinctly different frequency band. Combination-sensitive neurons respond selectively to acoustic elements of sonar echoes or social vocalizations. In mustached bats, this response property originates in high-frequency representations of the inferior colliculus (IC) and depends on low and high frequency-tuned glycinergic inputs. To identify the source of these inputs, we combined glycine immunohistochemistry with retrograde tract tracing. Tracers were deposited at high-frequency (>56 kHz), combination-sensitive recording sites in IC. Most glycine-immunopositive, retrogradely labeled cells were in ipsilateral ventral and intermediate nuclei of the lateral lemniscus (VNLL and INLL), with some double labeling in ipsilateral lateral and medial superior olivary nuclei (LSO and MSO). Generally, double-labeled cells were in expected high-frequency tonotopic areas, but some VNLL and INLL labeling appeared to be in low-frequency representations. To test whether these nuclei provide low frequency-tuned input to the high-frequency IC, we combined retrograde tracing from IC combination-sensitive sites with anterograde tracing from low frequency-tuned sites in the anteroventral cochlear nucleus (AVCN). Only VNLL and INLL contained retrogradely labeled cells near (≤50 μm) anterogradely labeled boutons. These cells likely receive excitatory low-frequency input from AVCN. Results suggest that combination-sensitive facilitation arises through convergence of high-frequency glycinergic inputs from VNLL, INLL, or MSO and low-frequency glycinergic inputs from VNLL or INLL. This work establishes an anatomical basis for spectrotemporal integration in the auditory midbrain and a functional role for monaural nuclei of the lateral lemniscus.     

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 ir 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 electrophysi ological 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 morpholo 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 morpholo 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 centr 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 concentra tions of PL endings come from the ipsilateral lateral superior olive. In combination with inputs from the contralateral dorsal nucleus of the lateral lemniscus, PL endings from the superior olive may participate in many inhibitory synapses found in the central nucleus. These different patterns of synaptic input from the superior olivary complex will influence how binaural information is transmitted to the inferior colliculus. © 1995 Wiley-Liss, Inc.     

Fibroblast growth factor-2-like immunoreactivity in auditory brainstem nuclei of the developing and adult rat: Correlation with onset and loss of hearing

Fibroblast growth factor-2 (FGF-2; basic FGF) is widely distributed in the developing and adult brain and has numerous effects on cultured and lesioned neural cells. The physiological role of FGF-2 in the unlesioned nervous system, however, is still not understood. We have studied the distribution of FGF-2 in the developing, adult, and functionally impaired central auditory system of the rat using specific antibodies and peroxidase-antiperoxidase immunocytochemistry. FGF-2-like immunoreactivity (FGF-2-IR) occurred in neuronal cell bodies and/or nerve fibers but was very rarely observed in glial cells. Several auditory brainstem nuclei, including the superior paraolivary nucleus, the medial superior olive, the lateral and ventral trapezoid nuclei, and the central nucleus, as well as the external cortex of the inferior colliculus, were entirely devoid of FGF-2-IR. In the dorsal cochlear nucleus, the lateral superior olive, and the nuclei of the lateral lemniscus, FGF-2-IR was not detectable in nerve cell bodies prior to adult age. Neurons in the medial geniculate body exhibited FGF-2-IR only transiently, from postnatal day (P) 5 until P16. Neurons in the medial nucleus of the trapezoid body were immunoreactive from P8 onwards. FGF-2-IR in anteroventral and posteroventral cochlear neurons disappeared at P14, i. e., at the onset of hearing, but immunoreactivity returned after P21. A transient expression of FGF-2 around the time when hearing function commences was observed in the dorsal cortex of the inferior colliculus. Thus, regulation of neuronal FGF-2-IR in several, but not all, auditory, nuclei is related to the onset of hearing, in that IR disappears at that time or transiently appears. This suggests a causal link between the onset of hearing and FGF-2 expression. In support of this notion, ototoxic treatment with gentamycin abolished FGF-2-IR in the P16 medial geniculate body but not in other auditory brainstem centers. Thus, FGF-2 may be considered a regulator or indicator of the acquisition of functional activity and responsiveness to sensory stimuli in several areas of the auditory system. © 1995 Wiley-Liss, Inc.     

The effects of experimental brain-stem ischaemia on brain-stem auditory evoked potentials in primates.

We related intracranial auditory brain-stem evoked potentials (BAEPs) to the surface BAEP using a model of focal brain-stem ischaemia. In 17 baboons anaesthetised with alpha-chloralose, BAEPs were recorded bilaterally at the mastoids and in the caudal lateral lemniscus (LL) and inferior colliculus (IC), in response to monaural click stimulation. Electrodes at these sites were each connected to the positive input of a differential amplifier, and one other electrode, placed at the vertex, was connected to all the negative inputs. Measurements of local cerebral blood flow (CBF) by hydrogen clearance were made at the LL and IC sites. The LL wave form contained 5-7 positive peaks, the second (B wave) being dominant and coinciding with the negative wave II of the surface BAEP. Following graded ischaemia, produced by basilar artery occlusion and controlled hypotension, the latency changes of these two peaks were significantly correlated, as were those of the third wave (C wave) of the LL response and the surface wave III. In the IC, the contralateral wave form contained 4 positive waves (A-D) and a later, dominant, slow negative wave; changes in its peak latency and those of the slow negative surface wave were similarly correlated. The thresholds of local CBF for increases in latency of waves B and C in the LL were similar (12-15 ml/100 g/min), but in the IC the thresholds were 20, 30-35 and 20-24 ml/100 g/min for the B, C and slow negative waves, respectively. Our data indicate that a gradient of sensitivity to ischaemia is present along the brain-stem auditory pathways; this could explain the earlier change of the late, rather than early, BAEP components as reported in clinical cases involving brain-stem lesions.