Medial Superior Olivary Nucleus Research Articles

Episodic exposure to ethanol during development differentially affects brainstem nuclei in the macaque.

Neuronal vulnerability to ethanol may be non-specific, i.e., vulnerability may be conferred by the developmental state of the population or by the site of derivation. To address these issues, the effect of developmental exposure to ethanol on three brainstem nuclei; the trigeminal motor (MoV), facial motor (MoVII) and medial superior olivary (MSO) nuclei was determined. MoVII and MSO are generated at the same time and from the same rhombomere, r4. MoV is generated earlier from r2. Macaca nemestrina were exposed to ethanol or a control solution one day per week for six or 24 weeks of gestation. Brainstems of the mature offspring were sectioned and stained. The number of neurons and volume of each nucleus were determined stereologically. Neuron number was lower in MoV and MSO following exposure to ethanol whereas MoVII appeared unaffected. No significant effects of ethanol exposure were seen on the volume and weight of the brainstem, or the volume of the individual nuclei. These findings show that ethanol differentially affects brainstem nuclei in a targeted, rather than non-specific, manner. Furthermore, they show that serious ethanol-induced neurological deficits can be present without gross morphological changes.

Local collateral projections from the medial superior olive to the superior paraolivary nucleus in the gerbil

Local collateral projections from the medial superior olivary nucleus in the gerbil auditory brainstem were examined to study the possible communication of this nucleus with periolivary cell groups. The projections were investigated using intracellular and extracellular labeling with Biocytin in the medial superior olive (MSO) in brainstem tissue slices. Collateral axons were found to branch from the main axons of the central cells of the MSO as the latter passed through a dorsally neighboring periolivary nucleus, the superior paraolivary nucleus (SPN), toward the ipsilateral inferior colliculus (IC), their traditionally accepted target. Bouton-like endings and en passant varicosities of these collaterals appeared to contact the somata and proximal dendrites of cells within the SPN. Furthermore, close observation revealed that these collaterals terminate on at least two types of SPN cells. Intracellular labeling of the collateral axons of the MSO neurons combined with retrograde prelabeling of their target cells, however, revealed that the collaterals selectively contact the cells of the SPN that project to the ipsilateral IC. A link between the MSO and SPN has not been reported previously. This connection is of interest since SPN cells themselves project either to the cochlear nuclei (CN) or the IC. The MSO–SPN projection identified here raises the possibility that the latter may serve as an ancillary channel to convey MSO information to the IC.

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.

Immunfluorescence study of neuropeptides in identified neurons of the rat auditory superior olivary complex.

The present study was conducted to investigate the distribution and immunohistochemical characteristics of ascending and descending projection neurons of the rat superior olivary complex (SOC), a group of interrelated brainstem nuclei. Ascending neurons were identified by injection of cholera toxin B subunit (CTB) into the central nucleus of the inferior colliculus (IC), descending neurons were labeled by application of Fluoro-Gold (FG) into the scala tympani of the cochlea, ipsilaterally to the IC injection. In accordance with the literature, we observed neurons innervating the IC located in the lateral superior olivary nucleus (LSO) and dorsal periolivary groups (DPO) on both sides, in the superior paraolivary nucleus (SPO) predominantly ipsilateral, as well as in the ipsilateral medial superior olivary nucleus (MSO) and the medial nucleus of the trapezoid body (MNTB). Cochlear projection neurons were found predominantly in the ipsilateral LSO as well as in the bilateral SPO, DPO, MSO and MNTB. In addition, a considerable population of neurons in the ipsilateral LSO and SPO were identified as being both ascending and descending. To further characterize these double-projecting neurons, brainstem sections were incubated in antisera directed against different neuroactive substances. The majority of ascending/descending cells in the LSO contained calcitonin gene-related peptide, but not substance P (SP), met-enkephalin (ENK) or tyrosine hydroxylase (TH). Some of these neurons apparently were contacted by ENK- or SP-immunoreactive fibers and terminals. In addition, we found TH-immunoreactive neurons in the lateral MNTB region. These neurons, which were labeled upon tracer injection into the cochlea (but not upon IC injection), probably belong to the C1 catecholaminergic cell group and may represent a division of the uncrossed olivocochlear bundle. The present results reveal the existence of a previously unknown subpopulation of SOC neurons that project to both the cochlea and the inferior colliculus. Their CGRP immunoreactivity and their uncrossed projection pattern provide evidence that they may belong to the cholinergic, putatively excitatory cell group.

Effects of unilateral cochlear removal on dendrites in the gerbil medial superior olivary nucleus.

For most neurons, dendrites serve as the major pathway for incoming activity from other neurons. It might therefore be expected that dendrites are particularly sensitive to variations in the level of afferent input they receive. In the auditory brainstem, this expectation has been confirmed in neurons of the medial superior olivary nucleus (MSO). The MSO is uniquely suited to studies of afferent influences on dendrites, as lateral and medial dendrites of MSO neurons receive inputs almost exclusively from the ipsilateral and contralateral ears, respectively. Thus, the effects of unilateral afferent manipulations may be compared between defined dendrites on the same neurons. We have used unilateral deafening (by surgical destruction of the cochlea) in immature [postnatal day 18 (P18)] and adult gerbils to study the late maturation and effect of peripheral deafferentation on the dendrites of MSO neurons. In semi-thin, frontal sections from unoperated animals, we found a change between P18 and adulthood from a lateral to a medial bias in the symmetry of MSO dendrites. Cochlear removal in adulthood led to a reduction in the density of dendritic profiles on the side of the ablation in both MSOs. Cochlear removal at P18 led to a rapid (< 3 days) and sustained dendritic atrophy that was most marked in the caudal part of the nucleus. Electron microscope (EM) measurements in the sagittal plane on MSO dendrite profiles of animals unilaterally deafened at P18 showed a reduction in the number, but not in the area, of profiles on the side of the deafened ear. These results demonstrate a developmental change in the symmetry of MSO medial and lateral dendrites, and a rapid and long-lasting reduction in the number of distal dendrites produced by unilateral deafening either in infancy or adulthood.

A network model for the functional architecture of the mammalian medial superior olivary nucleus

The mammalian MSO is part of the superior olivary complex, the lowest level in the auditory pathway, which receives binaural input. The microarchitecture of the anatomical convergence of both paths is considered as fundamental for the nucleus’ function in time-domain processing. This architecture is mostly, according to a proposal of Jefress [L. Jefress, J. Comp. Physiol. Psychol., 35–39 (1948)], interpreted as a network of coincidence detectors. However, the topographic organization of the afferent innervation of the MSO shows much more complexity as is assumed in this model. The connection scheme of the afferent fibers indicates even aspects of terminal divergence, which should result in broadly tuned neurons instead of sharply tuned coincidence detectors. This study proposes a network model for the processing of interaural time delays (ITD) in the MSO based on connection patterns and response properties of the MSO fusiform cells. Instead of local coincidence detection, coding of ITD’s is distributed over a cluster of fusiform cells, where each individual cell’s degree of stimulus resolution is considered as low. While in the Jefress model each delay line is processed as a single channel, cluster formation based on MSO’s multipolar cells could be a mechanism for sampling over these different channels.

Refractory properties of auditory brain-stem responses evoked by electrical stimulation of human cochlear nucleus: evidence of neural generators

In this study of electrically-evoked auditory brain-stem responses (EABRs) elicited by cochlear nucleus stimulation, 3 waves were identified after the initial wave that is directly initiated by the electric stimulus. Varying the rate of periodic stimulation or the interval between pairs of stimuli revealed that the shorter the latency of a wave, the faster it recovered from activation (i.e. shorter refractory period). The slow recovery of the third wave and an accompanying contribution to the second wave could be accounted for by postsynaptic generation in the two medial superior olivary nuclei (MSO); the faster recovery of another contribution to the second wave by generation in an axonal tract bending around the contralateral MSO; and the fastest recovery of the first wave by another axonal pathway having larger axons. Comparison with the relative latencies and spatial distribution of an acoustically-evoked auditory brain-stem response (AABR) indicated that the third wave corresponds to wave V, the second to wave IV (called IVb), and the first to a wave that precedes wave IV (called IVa). The anatomical interpretations for the two later waves of the EABR are consistent with most of the extant data on the neural generators of AABR waves IV and V. Thus, the present data and analysis strengthen the identification of the electrically evoked responses as EABRs and provide a firmer foundation for intra-operative EABR monitoring to assist auditory brain-stem implant placement.

Immunohistochemical localization of neurocan in the lower auditory nuclei of the dog

Chondroitin sulfate proteoglycans are present at high levels in the lower auditory system of mammals. Axon terminals on the principal neurons in the superior olivary nuclei contain chondroitin 4- and 6-sulfate, while the broad extracellular matrix around axon terminals contains chondroitin sulfate D, a highly sulfated chondroitin sulfate rich in the disaccharide unit of GlcA(2S)β1→3GalNAc(6S), in the dog. In the present study, we investigated the immunohistochemical staining of neurocan, a brain-specific proteoglycan, in the lower auditory tract of the dog, including an analysis by immunoelectron microscopy. Immunolocalization of neurocan was conspicuous in the medial and lateral superior olivary nuclei and much less intense immunostaining was seen in the cochlear nucleus and posterior colliculus. No immunoreactivity were found in other nuclei. The immunostaining in the medial and lateral superior olivary nuclei was observed as perineuronal nets around large principal neurons at the light-microscopic level, while no immunostaining was observed in the upper segment of the medial superior olivary nucleus and the medial segment of the lateral superior olivary nucleus, in which medium-sized and small neurons were located. Immunoelectron microscopy revealed the reaction products of immunostaining on cell membranes of the perikarya of principal neurons and on cell membranes of presynaptic terminals which made axo-somatic synapses on the principal cells. No immunoreactivity was detected at synaptic junctions, in the extracellular matrix or within axon terminals. In the cochlear nucleus, immunoreactive perineuronal nets were found around a small number of neurons and immunoreactive nerve fibers were scattered in the anterior ventral cochlear nucleus. In the posterior colliculus, perineuronal nets, which were weakly immunostained, were sparsely distributed in the central nucleus. These results suggest that different locations of chondroitin sulfate proteoglycans, including neurocan, may be associated with focal sites composed of neuronal surface, terminal boutons and extracellular matrix in the lower auditory tract of the adult dog.

Effect of Adult-Onset Deafness on the Human Central Auditory System

Degenerative change in the central auditory system was assessed in seven subjects with profound bilateral adult-onset deafness. The degree of transneuronal atrophy was determined by measuring cell size at three levels of the brain stem auditory pathway (anteroventral cochlear nucleus, medial superior olivary nucleus, and inferior colliculus). Within subjects, the relative degree of cell shrinkage was similar across all levels of the central pathway. Across subjects, the best neuronal preservation was seen in a case of viral labyrinthitis with 1 year of bilateral dearness and a near-normal population of cochlear ganglion cells. Reduction in cell size was greatest in cases of bacterial labyrinthitis or Scheibe degeneration with reduced populations of ganglion cells and longer periods of deafness. At the level of the cochlear nucleus, there was no consistent difference in cell size between the side stimulated by a functioning prosthetic device and the nonstimulated side.

Somatostatin and substance P-like immunoreactivity in the auditory brainstem of the adult rat

The superior olivary complex (SOC) of the adult rat brainstem was studied in detail with regard to its innervation by neural elements showing immunoreactivity for two neuroactive peptides, somatostatin and substance P. Nerve fibres and varicosities showing positive immuno-reactivity for both peptides were particularly dense immediately dorsal and lateral to the lateral superior olivary nucleus (LSO) and dorsal to the superior paraolivary nucleus (SPN). Penetration of this curtain-like innervation into the SPN was limited, and the LSO showed only a very minor innervation by somatostatin-positive structures in its most medial (high frequency) lobe. Dense fibre labelling and varicosities were also apparent for both peptides immediately medial to the ventral and dorsal nuclei of the lateral lemniscus, and in the external cortex and dorsomedial zones of the inferior colliculus (IC). Labelled fibres and endings were also seen in the granule cell regions of anteroventral cochlear nucleus (AVCN) and the most dorsomedial parts of the dorsal cochlear nucleus (DCN). The majority of cells in the medial nucleus of the trapezoid body (MNTB) showed a prominent innervation by nerve terminals that stained positive for somatostatin only whereas the medial superior olivary nucleus (MSO) was devoid of label for both peptides. The ventral nucleus of the trapezoid body (VNTB) showed sparse but significant innervation by both somatostatin and substance P-positive structures. Hence the VNTB was the only defined nucleus of the SOC to show a significant substance P-positive innervation. Neuronal somata immuno-reactive for somatostatin were found in anteroventral and posteroventral cochlear nuclei (AVCN and PVCN) and the A5 and A7 cell groups adjacent to the LSO and the VNLL and DNLL and in all subdivisions of the inferior colliculus (IC). Somata showing only faint immunoreactivity for substance P were found in the VNLL, AVCN and PVCN. These results suggest a potential role for both peptides in auditory signal processing in the adult rat brain.

Expression of Calcium Binding Proteins in the Auditory Brainstem Pathway of the Jaundiced Gunn Rat † 829

Sensorineural hearing loss is one of the major sequelae of neonatal hyperbilirubinemia. Retrocochlear sites of lesions due to kernicterus are related to significant abnormalities in the wave latencies, interwave intervals, and amplitudes of the auditory brainstem response. In the present study, changes in the expression of the calcium binding proteins (CBP) parvalbumin and calbindin-D28k have been examined in the homozygous recessive jaundiced (jj) Gunn rat by light microscopic immunohistochemistry at 15-18 days postnatally. The density of immunoreactive staining for both CBPs was reduced in the cochlear nuclei and the superior olivary complex, particularly the superior paraolivary and medial superior olivary nuclei, in comparison to age-matched heterozygous (Nj) control rats. At both sites, the extent of the reduction in immunoreactivity was related to the severity of the clinical symptoms. By contrast, immunoreactive staining in other brainstem auditory(e.g., dorsal and ventral nuclei of the lateral lemniscus, inferior colliculus, medial geniculate body) and neighboring non-auditory structures was similar in jaundiced and control rats. The developmental retardation of CBPs coincides with the period of synaptic refinement in the auditory brainstem, and the inability to buffer intracellular calcium effectively may lead to bilirubin-induced neuronal cell death, possibly by inhibition of Ca2+/calmodulin-dependent kinase II activity.

Axonal morphology in fibrodendritic laminae of the dorsal nucleus of the lateral lemniscus: Afferent projections from the medial superior olivary nucleus

The distribution and morphology of axons projecting from the medial superior olivary nucleus to the dorsal nucleus of the lateral lemniscus were studied in the adult cat. Injections of Phaseolus vulgaris-leucoagglutinin, biocytin, or dextran-rhodamine in the medial superior olivary nucleus labeled axons that ascended in the lateral lemniscus. Before entering the inferior colliculus, collateral branches of these labeled axons ended in the dorsal nucleus of the lateral lemniscus in thin, horizontal bands forming laminae that extended throughout the rostral-caudal length of the dorsal nucleus of the lateral lemniscus. A dorsal-ventral topography was apparent in the position of the lamina with respect to the injection site, but no relation between the rostral-caudal location of labeled endings and the injection site was observed. There was a divergent pattern of connections within the horizontal laminae rather than a point-to-point organization. The terminal branches of the collateral axons exhibited round or oval boutons en passant and terminaux. Individual arbors reconstructed from serial sections distributed varicosities in circumscribed domains that were only a subcomponent of the area of the afferent laminae in which they were distributed. The spatial relationships of axonal domains of several axons labeled from a single injection in the medial superior olivary nucleus suggest a mosaic pattern in the laminar connections with the dorsal nucleus of the lateral lemniscus.

Morphometric development of the human fetal auditory system: inferior collicular nucleus

The development of the human inferior collicular nucleus was studied on serial sections of the brains of 9 fetuses at 12–34 weeks of gestation and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis of the development of the inferior collicular nucleus showed that its development accelerates after 18 weeks of gestation in terms of the columnar volume and length, size of neurons and circularity ratio. Large-sized neurons 2–3 times the area of small-sized neurons appeared after 18 weeks of gestation. The ratio of large neurons to the total ranged between 3 and 6% in the inferior collicular nucleus. The development of the inferior collicular nucleus was similar to that of the ventral cochlear nucleus and the medial superior olivary nucleus.

Auditory Deficits and Hearing Loss Associated with Focal Brainstem Haemorrhage

Four cases of central pontine haemorrhage are described in which auditory dysfunction was documented. Two cases had a hearing loss, in one of which there was recovery of the low frequencies. This case provides support for the tonotopic organization of the auditory pathways in the caudal pontine area, with the lowest frequencies being encoded medially. In all cases, there were abnormalities of the auditory brainstem responses, wave V being consistently involved, while wave III was abnormal in only one patient. In three cases, the masking level differences and crossed acoustic reflex thresholds were abnormal. The ipsilateral reflex thresholds were normal at least on one side in all cases. In the patient with the most significant hearing loss, loudness recruitment, assessed both psychophysically and with the acoustic reflex thresholds, was evident. These data are interpreted in terms of there being damage to the medial superior olivary nuclei and trapezoid body involving both afferent and efferent fibres.

Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization

This study was concerned with the distribution of a variety of putative neuromodulator and neurotransmitter systems in auditory regions of the rat brainstem using in situ hybridization histochemistry. Serial brain sections were screened for the presence of mRNAs for (i) precursors of the neuroactive substances cholecystokinin, somatostatin, proenkephalin and substance P (preprotachykinin), (ii) glutamic acid decarboxylase, the key synthesizing enzyme for GABA, or (iii) subunits αl, α2 and α3 of the GABA A receptor. Detectable message for all of these probes was found in at least one auditory brainstem area. There were clear differences in the distribution of the various mRNAs in subregions of the inferior colliculus, superior olivary complex, lateral lemniscus and cochlear nucleus. Cells expressing mRNA for glutamic acid decarboxylase were most prominent in the inferior colliculus, but were also present in all lower auditory brainstem nuclei, except the medial superior olivary nucleus and medial nucleus of trapezoid body. The mRNA for GABA Aα1 receptor subunits was detectable in all auditory regions investigated, although at different levels of expression. GABA Aα2 and α3 mRNA signals were seen in inferior colliculus, lateral lemniscus and in almost all superior olivary complex regions, but in fewer cells and at lower levels than the GABA Aα1 subtype. Moderate to high levels of preprocholecystokinin mRNA expression were seen in all subregions of the inferior colliculus. In other auditory brainstem areas, preprocholecystokinin mRNA levels were either low or absent. With regard to mRNAs for the neuroactive peptides somatostatin, preprotachykinin and preproenkephalin, all were expressed in the inferior colliculus but there were differences in their cellular distribution. For example, there were almost no preprotachykinin mRNA expressing cells in the central nucleus of inferior colliculus and levels of somatostatin mRNA were especially high in the dorsal cortex and in layer 3 of the external cortex of inferior colliculus. There were also differences in the pattern of expression of these mRNAs in the various brainstem auditory nuclei; there was no preprotachykinin mRNA in any part of the superior olivary complex, only somatostatin mRNA was found in the ventral cochlear nucleus, and expression of preproenkephalin mRNA was pronounced in the ventral nucleus of the trapezoid body and the rostral periolivary zone. The data are considered in light of the connectivity and functional organization of the auditory brainstem.

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)

Development of glycinergic cells and puncta in nuclei of the superior olivary complex of the postnatal ferret

The distribution of glycine-immunopositive cells and axonal endings was studied in the adult and early postnatal ferret superior olive. As in other species, the most prominent glycine-immunopositive cell group in the adult ferret superior olive was the medial nucleus of the trapezoid body. Other darkly immunostained cells were present, although more scattered, in most periolivary regions, including the lateral and ventral trapezoid body nuclei. In the lateral superior olivary nuclei, glycine-immunopositive cells were intermingled with immunonegative cells. A comparable population of cells in the ipsilateral lateral superior olivary nucleus was retrogradely labeled in cases with unilateral injections of tritiated glycine in the inferior colliculus. Glycine-immunopositive puncta were widely distributed in the neuropil in most periolivary regions, including dense accumulations in the dorsomedial periolivary region and ventral and lateral nuclei of the trapezoid body. In the lateral and medial superior olivary nuclei, immunopositive puncta were distributed around the principal cells in characteristic perisomatic halos. In postnatal ferrets, immunopositive cell bodies were first observed by postnatal day 7 and were distributed in regions comparable to regions in the adult, with the exception that immunopositive cells in the lateral superior olivary nucleus did not appear until about postnatal day 28. There was diffuse staining in the neuropil in principal and periolivary nuclei by postnatal day 7. During the third postnatal week, the immunostaining in the neuropil began to take on a more granular appearance and immunopositive puncta could be seen by postnatal day 35. In the lateral and medial superior olivary nuclei, the earliest distribution of immunostaining in the neuropil was nonuniform, being greater in the high-frequency, medial, and ventral regions, respectively. The density gradient in these areas was gradually eliminated over the next 2 postnatal weeks as immunostained processes and endings appeared over greater portions of the nuclei.

Localization of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor mRNAs in rat brain

Parathyroid hormone (PTH)-related peptide (PTHrP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP mRNA is also expressed in a variety of non-malignant tissues, suggesting that PTHrP is an endogenous peptide with as-yet unidentified autocrine or paracrine functions in normal tissues, including brain (Weir et al., Proc. Natl. Acad. Sci., 87 (1990) 108-112). In the present study, we used in situ hybridization to examine the expression of PTHrP and the common receptor for PTH and PTHrP in adult rat brain. Widespread yet anatomically discrete patterns of hybridization were observed using 35S-labeled antisense cRNA probes. PTHrP gene expression was highest in the supramamillary nucleus of the hypothalamus, medial superior olivary nucleus, and in subpopulations of cells in the neostriatum, hippocampus, and cerebral cortex. Other major sites of PTHrP gene expression included the amygdala, midline thalamic nuclei, pontine nuclei, choroid plexus, and the anterior pituitary gland. Highest levels of PTH/PTHrP receptor mRNA were in the mesencephalic portion of the trigeminal nucleus and the trigeminal ganglion, the lateral reticular, pontine and reticulotegmental nuclei, the hypoglossal nucleus and area postrema. Other major sites of PTH/PTHrP receptor expression included the anterodorsal nucleus of the thalamus, basolateral amygdala, entorhinal cortex, parasubiculum, cells in the Purkinje cell layer of the cerebellum, vestibular nuclei, ventral cochlear nucleus, the motor nucleus of the trigeminal, and the facial and external cuneate nuclei. The expression of genes encoding PTHrP and its receptor in discrete areas of the brain suggests that PTHrP may function as a neurotransmitter in the central nervous system.

Development of the human medial superior olivary nucleus: a morphometric study

The development of the human medial superior olivary nucleus was studied in serial sections of 10 fetuses at 12–35 weeks of gestation (WG), an infant at 2 months of age and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis suggested that the development of the human medial superior olivary nucleus accelerates between 16 and 21 WG in terms of columnar lengths and volumes, neuronal sizes and circularity ratios, while it matures gradually in terms of the amount of Nissl bodies.

Projections from the lateral nucleus of the trapezoid body to the medial superior olivary nucleus in the gerbil

We made small injections of horseradish peroxidase into the medial superior olivary nucleus (MSO) of gerbils in order to examine the sources of input into that nucleus. As previously described, the MSO receives inputs from neurons in the rostral part of both anteroventral cochlear nuclei. In addition, we found evidence for a projection from the ipsilateral lateral nucleus of the trapezoid body (LNTB). Our results are also compatible with previous reports that the medial nucleus of the trapezoid body (MNTB) projects to the MSO. It is likely that these projections into the MSO from the LNTB and MNTB are sources of inhibitory synaptic inputs.