Medial Superior Olivary Nucleus Research Articles

Structural Refinement of the Auditory Brainstem Neurons in Baboons During Perinatal Development.

Children born prematurely suffer from learning disabilities and exhibit reading, speech, and cognitive difficulties, which are associated with an auditory processing disorder. However, it is unknown whether gestational age at delivery and the unnatural auditory environment in neonatal intensive care units (NICU) collectively affect proper auditory development and neuronal circuitry in premature newborns. We morphologically characterized fetal development of the medial superior olivary nucleus (MSO), an area important for binaural hearing and sound localization, in the auditory brainstem of baboon neonates at different gestational ages. Axonal and synaptic structures and the tonotopic differentiation of ion channels in the MSO underwent profound refinements after hearing onset in the uterus. These developmental refinements of the MSO were significantly altered in preterm baboon neonates in the NICU. Thus, the maternal environment in uterus is critical for auditory nervous system development during the last trimester of pregnancy and critically affects the anatomic and functional formation of synapses and neural circuitry in the preterm newborn brain.

Human Superior Olivary Nucleus Neuron Populations in Subjects With Normal Hearing and Presbycusis.

Normative data on superior olivary nucleus neuron counts derived from human specimens are sparse, and little is known about their coherence with structure and function of the cochlea. The purpose of this study was to quantify the neuron populations of the divisions of the superior olivary nucleus in human subjects with normal hearing and presbycusis and investigate potential relationships between these findings and histopathology in the cochlea and hearing phenotype Methods: Histopathologic examination of temporal bone and brainstem specimens from 13 subjects having normal hearing or presbycusis was undertaken. The following was determined for each: number and density of superior olivary nucleus and cochlear nucleus neurons, inner and outer hair cell counts, spiral ganglion cell counts, and pure tone audiometry. The results demonstrate a significant relationship between cells within structures of the cochlear nucleus and the number of neurons of the medial superior olivary nucleus. No relationship between superior olivary nucleus neuron counts/density and cochlear histopathology or hearing phenotype was encountered. Normative data for superior olivary nucleus neuron populations are further established in the data presented in this study that includes subjects with normal hearing and also presbycusis.

Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus.

Experiments in several species have identified direct projections to the medial geniculate nucleus (MG) from cells in subcollicular auditory nuclei. Moreover, many cochlear nucleus cells that project to the MG send collateral projections to the inferior colliculus (IC) (Schofield et al., 2014). We conducted three experiments to characterize projections to the MG from the superior olivary and the lateral lemniscal regions in guinea pigs. For experiment 1, we made large injections of retrograde tracer into the MG. Labeled cells were most numerous in the superior paraolivary nucleus, ventral nucleus of the trapezoid body, lateral superior olivary nucleus, ventral nucleus of the lateral lemniscus, ventrolateral tegmental nucleus, paralemniscal region and sagulum. Additional sources include other periolivary nuclei and the medial superior olivary nucleus. The projections are bilateral with an ipsilateral dominance (66%). For experiment 2, we injected tracer into individual MG subdivisions. The results show that the subcollicular projections terminate primarily in the medial MG, with the dorsal MG a secondary target. The variety of projecting nuclei suggest a range of functions, including monaural and binaural aspects of hearing. These direct projections could provide the thalamus with some of the earliest (i.e., fastest) information regarding acoustic stimuli. For experiment 3, we made large injections of different retrograde tracers into one MG and the homolateral IC to identify cells that project to both targets. Such cells were numerous and distributed across many of the nuclei listed above, mostly ipsilateral to the injections. The prominence of the collateral projections suggests that the same information is delivered to both the IC and the MG, or perhaps that a common signal is being delivered as a preparatory indicator or temporal reference point. The results are discussed from functional and evolutionary perspectives.

Alteration of glycine receptor immunoreactivity in the auditory brainstem of mice following three months of exposure to radiofrequency radiation at SAR 4.0 W/kg.

The increasing use of mobile communication has triggered an interest in its possible effects on the regulation of neurotransmitter signals. Due to the close proximity of mobile phones to hearing-related brain regions during usage, its use may lead to a decrease in the ability to segregate sounds, leading to serious auditory dysfunction caused by the prolonged exposure to radiofrequency (RF) radiation. The interplay among auditory processing, excitation and inhibitory molecule interactions plays a major role in auditory function. In particular, inhibitory molecules, such a glycine, are predominantly localized in the auditory brainstem. However, the effects of exposure to RF radiation on auditory function have not been reported to date. Thus, the aim of the present study was to investigate the effects of exposure to RF radiation on glycine receptor (GlyR) immunoreactivity (IR) in the auditory brainstem region at 835 MHz with a specific absorption rate of 4.0 W/kg for three months using free-floating immunohistochemistry. Compared with the sham control (SC) group, a significant loss of staining intensity of neuropils and cells in the different subdivisions of the auditory brainstem regions was observed in the mice exposed to RF radiation (E4 group). A decrease in the number of GlyR immunoreactive cells was also noted in the cochlear nuclear complex [anteroventral cochlear nucleus (AVCN), 31.09%; dorsal cochlear nucleus (DCN), 14.08%; posteroventral cochlear nucleus (PVCN), 32.79%] and the superior olivary complex (SOC) [lateral superior olivary nucleus (LSO), 36.85%; superior paraolivary nucleus (SPN), 24.33%, medial superior olivary nucleus (MSO), 23.23%; medial nucleus of the trapezoid body (MNTB), 10.15%] of the mice in the E4 group. Auditory brainstem response (ABR) analysis also revealed a significant threshold elevation of in the exposed (E4) group, which may be associated with auditory dysfunction. The present study suggests that the auditory brainstem region is susceptible to chronic exposure to RF radiation, which may affect the function of the central auditory system.

Differential conduction velocity regulation in ipsilateral and contralateral collaterals innervating brainstem coincidence detector neurons.

Information processing in the brain relies on precise timing of signal propagation. The highly conserved neuronal network for computing spatial representations of acoustic signals resolves microsecond timing of sounds processed by the two ears. As such, it provides an excellent model for understanding how precise temporal regulation of neuronal signals is achieved and maintained. The well described avian and mammalian brainstem circuit for computation of interaural time differences is composed of monaural cells in the cochlear nucleus (CN; nucleus magnocellularis in birds) projecting to binaurally innervated coincidence detection neurons in the medial superior olivary nucleus (MSO) in mammals or nucleus laminaris (NL) in birds. Individual axons from CN neurons issue a single axon that bifurcates into an ipsilateral branch and a contralateral branch that innervate segregated dendritic regions of the MSO/NL coincidence detector neurons. We measured conduction velocities of the ipsilateral and contralateral branches of these bifurcating axon collaterals in the chicken by antidromic stimulation of two sites along each branch and whole-cell recordings in the parent neurons. At the end of each experiment, the individual CN neuron and its axon collaterals were filled with dye. We show that the two collaterals of a single axon adjust the conduction velocities individually to achieve the specific conduction velocities essential for precise temporal integration of information from the two ears, as required for sound localization. More generally, these results suggest that individual axonal segments in the CNS interact locally with surrounding neural structures to determine conduction velocity.

Altered brainstem auditory evoked potentials in a rat central sensitization model are similar to those in migraine

Migraine symptoms often include auditory discomfort. Nitroglycerin (NTG)-triggered central sensitization (CS) provides a rodent model of migraine, but auditory brainstem pathways have not yet been studied in this example. Our objective was to examine brainstem auditory evoked potentials (BAEPs) in rat CS as a measure of possible auditory abnormalities. We used four subdermal electrodes to record horizontal (h) and vertical (v) dipole channel BAEPs before and after injection of NTG or saline. We measured the peak latencies (PLs), interpeak latencies (IPLs), and amplitudes for detectable waveforms evoked by 8, 16, or 32kHz auditory stimulation. At 8kHz stimulation, vertical channel positive PLs of waves 4, 5, and 6 (vP4, vP5, and vP6), and related IPLs from earlier negative or positive peaks (vN1–vP4, vN1–vP5, vN1–vP6; vP3–vP4, vP3–vP6) increased significantly 2h after NTG injection compared to the saline group. However, BAEP peak amplitudes at all frequencies, PLs and IPLs from the horizontal channel at all frequencies, and the vertical channel stimulated at 16 and 32kHz showed no significant/consistent change. For the first time in the rat CS model, we show that BAEP PLs and IPLs ranging from putative bilateral medial superior olivary nuclei (P4) to the more rostral structures such as the medial geniculate body (P6) were prolonged 2h after NTG administration. These BAEP alterations could reflect changes in neurotransmitters and/or hypoperfusion in the midbrain. The similarity of our results with previous human studies further validates the rodent CS model for future migraine research.

Patterns of convergence in the central nucleus of the inferior colliculus of the Mongolian gerbil: organization of inputs from the superior olivary complex in the low frequency representation.

Projections to the inferior colliculus (IC) from the lateral and medial superior olivary nuclei (LSO and MSO) were studied in the gerbil (Meriones unguiculatus) with neuroanatomical tract-tracing methods. The terminal fields of projecting axons were labeled via anterograde transport of biotinylated dextran amine (BDA) and were localized on series of horizontal sections through the IC. In addition, to make the results easier to visualize in three dimensions and to facilitate comparisons among cases, the data were also reconstructed into the transverse plane. The results show that the terminal fields from the low frequency parts of the LSO and MSO are concentrated in a dorsal, lateral, and rostral area that is referred to as the “pars lateralis” of the central nucleus by analogy with the cat. This region also receives substantial input from both the contralateral and ipsilateral cochlear nuclei (Cant and Benson, 2008) and presumably plays a major role in processing binaural, low frequency information. The basic pattern of organization in the gerbil IC is similar to that of other rodents, although the low frequency part of the central nucleus in gerbils appears to be relatively greater than in the rat, consistent with differences in the audiograms of the two species.

Neuroanatomical dysmorphology of the medial superior olivary nucleus in sudden fetal and infant death

This study expands our understanding of the organization of the human caudal pons, providing a morphologic characterization of the medial superior olivary nucleus (MSO), component of the superior olivary complex (SOC) that plays an important role in the processing of acoustic information. We examined victims of sudden unexplained fetal and infant death and controls (n = 75), from 25 gestational weeks to 8 months of postnatal age, by complete autopsy and in-depth autonomic nervous system histological examination, particularly of the MSO nucleus, the focus of this study. Peculiar cytoarchitectural features of the MSO nucleus were found in sudden death cases, such as hypoplasia/agenesis and immature hypercellularity, frequently related to dysgenesis of contiguous structures involved in respiratory rhythm-generating circuit, in particular to hypoplasia of the retrotrapezoid and the facial nuclei. We propose the involvement of this nucleus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities. Besides, we highlight the fundamental role of the maternal smoking in pregnancy as etiological factor in the dysmorphic neuroanatomical development of the MSO nucleus.

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.

Asymmetric excitatory synaptic dynamics underlie interaural time difference processing in the auditory system.

Author SummaryAnimals can locate the source of a sound by detecting microsecond differences in the arrival time of sound at the two ears. Neurons encoding these interaural time differences (ITDs) receive an excitatory synaptic input from each ear. They can perform a microsecond computation with excitatory synapses that have millisecond time scale because they are extremely sensitive to the input's “rise time,” the time taken to reach the peak of the synaptic input. Current theories assume that the biophysical properties of the two inputs are identical. We challenge this assumption by showing that the rise times of excitatory synaptic potentials driven by the ipsilateral ear are faster than those driven by the contralateral ear. Further, we present a computational model demonstrating that this disparity in rise times, together with the neurons' sensitivity to excitation's rise time, can endow ITD-encoding with microsecond resolution in the biologically relevant range. Our analysis also resolves a timing mismatch. The difference between contralateral and ipsilateral latencies is substantially larger than the relevant ITD range. We show how the rise time disparity compensates for this mismatch. Generalizing, we suggest that phasic-firing neurons—those that respond to rapidly, but not to slowly, changing stimuli—are selective to the temporal ordering of brief inputs. In a coincidence-detection computation the neuron will respond more robustly when a faster input leads a slower one, even if the inputs are brief and have similar amplitudes.

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.

Characterization of the rhesus monkey superior olivary complex by calcium binding proteins and synaptophysin

This study was performed in order to characterize the main nuclei of the rhesus monkey superior olivary complex by means of antibodies against the calcium binding proteins parvalbumin, calbindin and calretinin and the synaptic vesicle protein synaptophysin. These markers revealed the neuronal morphology and organization of nuclei located within the rhesus monkey superior olivary complex. The architectural details included the distribution of axonal terminals on neurons. The medial superior olivary nucleus was present as a column of neurons. No clear segregation of calretinin-positive terminals was noticed on the medial and lateral dendritic fields of these neurons. The lateral superior olivary nucleus was characterized by a distinct nuclear shape. Calretinin-, parvalbumin- or calbindin-positive terminals contacted somata and dendrites. The medial nucleus of trapezoid body could be clearly differentiated as a distinct region in the rhesus monkey superior olivary complex. Somata of that nucleus showed calbindin- and parvalbumin-labelling whereas somatic calyces of Held were reavealed by calretinin and synaptophysin labelling. The results are discussed with respect to the processing of acoustic information in primate species and their ability to hear high and low frequencies, which is reflected by anatomical correlates.

Effects of pentylenetetrazole and 4-aminopyridine on the auditory brainstem response (ABR) and on the hearing sensitivity in the guinea pig in vivo

For exploring a possible connection between the reduced hearing sensitivity and certain abnormalities in the auditory brainstem responses (ABRs) in generalized epilepsy, the effects of two convulsing agents, namely pentylenetetrazole (PTZ) and of 4-aminopyridine (4-AP), on: (1) the cortical activity (EEG), (2) the hearing threshold and (3) the amplitudes and latencies of the ABR waves evoked by a stimulus of high intensity (100 dB) were investigated in guinea pigs. All animals injected (i.p.) with 100 mg/kg PTZ or with 2 mg/kg 4-AP developed generalized seizures, followed by characteristic EEG patterns for the post-ictal period, that were accompanied by a marked reduction of the hearing sensitivity (as indicated by the elevated threshold of the ABR), as well as by retro-cochlear changes (as judged by the changes in the later ABR waves in response to 100 dB). For instance, both convulsing agents decreased the amplitude and increased the latency of P4, that is the wave component of the ABRs generated in the lateral superior olivary nucleus and while PTZ increased the latency of P3, the wave component of the ABRs generated in the medial superior olivary nucleus, 4-AP dramatically increased its amplitude. Comparison of recordings taken at specific times for the duration of the post-ictal period (i.e. within about 1 h for PTZ and 2 h for 4-AP) reveals that the extent of the changes on the EEG matches with the increase in the auditory threshold and with the extent of the changes on the later waves of the ABR elicited by 100 dB. These data indicate that changes in the activity of the lateral and the medial nuclei of the superior olivary complex (SOC) accompany the hearing loss and the post-ictal epileptic cortical activity.

Characterization of the human superior olivary complex by calcium binding proteins and neurofilament H (SMI-32).

This study provides a morphologic characterization of the human superior olivary complex as revealed by immunohistochemistry by using antibodies against the calcium binding proteins parvalbumin, calbindin, calretinin, and the nonphosphorylated neurofilament H SMI-32. By combining these markers, it was possible to establish the neuronal architecture and details of the morphologic organization (including axonal terminals) of the different nuclei. The medial superior olivary nucleus is formed by a sheet of parallel-oriented cells. A clear segregation of axon terminals was noticed on the medially and laterally oriented dendrites of the mostly bipolar neurons. The lateral superior olivary nucleus lacked a distinct nuclear shape but was formed by several patches of rather irregularly arranged neurons. Calretinin or parvalbumin immunoreactive afferent terminals were observed which contacted somata or dendrites of these neurons. The immunolabeling also revealed the boundaries of the dorsal periolivary nucleus and morphologic detail of its neurons. A coherent nuclear structure that could be addressed as the medial nucleus of the trapezoid body was not identified by any single one or by combinations of the markers used. The data were also used to establish a three-dimensional-reconstruction of the three major subnuclei of the superior olivary complex. The results are discussed with respect to the possible role of the superior olivary complex in the processing of spatial acoustic information in the azimuthal plane.

Ultrastructural transynaptic effects of unilateral cochlear ablation in the gerbil medial superior olive

This study investigated the long-term effects of unilateral hearing loss on the structure of synapses within the gerbil medial superior olivary (MSO) nuclei. Five animals had complete (surgical) left cochlear ablation at postnatal day 18. Previous studies have shown this to produce, within 3 days, significant transneuronal atrophy in the left dendritic field of both MSOs. Electron micrographs from sagittal ultrathin sections through the MSOs of the cochlear-ablated animals were compared to those from unoperated normals. Qualitatively, the ultrastructural features were similar. Most of the axodendritic terminals were R-type (round-type vesicles, putative excitatory) whereas, in the central part of the nucleus, predominated by neuron soma profiles, terminals of P- and F-type (pleomorphic- and flattened-type vesicles, putative inhibitory) were present in equal numbers with R-type terminals. F-type terminals were infrequent and occurred most around lateral parts of the MSO somata. These three types of terminals seen around the somata and proximal dendrites all had extended profiles with multiple, discontinuous appositions. Quantitative analysis revealed that R-type axodendritic terminals became smaller and less densely populated with vesicles where they synapsed onto the remaining dendrites arrayed towards the ablated side of both MSOs, and axosomatic P-type afferent terminals were smaller in the contralateral nuclei. A significant reduction in the number of terminals and synapses occurred in the central, somatic, region of the ipsilateral MSO. However, the terminal vesicle concentration in the remaining terminals increased. The results indicate that cochlear ablation can induce transynaptic reduction in the size of afferent axon terminals within the MSO, and alter their vesicle concentration. These changes are likely to affect the probability of transmitter release and thus influence their signaling power within the nucleus.

Changes in calcium-binding protein expression in the auditory brainstem nuclei of the jaundiced Gunn rat

Sensorineural hearing loss and auditory dysfunction are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the auditory brainstem pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that the expression of calcium-binding proteins may be altered in the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins, calbindin-D28k and parvalbumin, in the brainstem auditory pathway of homozygous recessive jaundiced ( jj) Gunn rats was examined by light and electron microscopic immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous ( Nj) littermate control rats. Immunoreactive staining for both calbindin and parvalbumin was reduced in the cochlear nuclei and the superior olivary complex in jj rats. The extent of the reduction in immunoreactivity was related to the severity of the clinical symptoms. By contrast, immunoreactive staining in other brainstem areas (e.g., dorsal and ventral nuclei of the lateral lemniscus, inferior colliculus), thalamic (medial geniculate body) auditory areas, and neighboring non-auditory structures was similar in jaundiced and control rats. Calbindin-immunoreactive staining in the superior paraolivary and medial superior olivary nuclei in Nj rats was associated with myelinated axons, whereas parvalbumin-immunoreactive staining was localized postsynaptically in neuronal somata and dendrites. Immunoreactive staining for the calcium-binding proteins calbindin and parvalbumin in lower brainstem auditory nuclei shows abnormalities in areas susceptible to the effects of hyperbilirubinemia and provides a sensitive new way to assess bilirubin toxicity in the auditory system.

Organization of olivocochlear neurons in the cat studied with the retrograde tracer cholera toxin-B.

We employed cholera toxin-B (CTB), an efficient retrograde tracer, to examine olivocochlear (OC) neurons in the cat. Our primary goals were (1). to determine whether the cat has two types of lateral OC (LOC) neurons as is found in certain rodents and (2). to document the morphology, number, and caudorostral distribution of OC neurons, bilaterally. Adult cats received injections of CTB through the round window of the left cochlea, and, after 3-6 days, the brains were sectioned transversely and CTB was revealed immunocytochemically in every section. In three cats, OC neurons were mapped, counted differentially according to cell group, and the numbers of each plotted bilaterally from caudal to rostral. In one cat, measurements were made on labeled LOC and medial OC (MOC) neurons. The results indicate that LOC neurons can be divided into two groups based on their proximity to the lateral superior olive (LSO): a more populous group of small neurons that have intimate contact with the LSO, designated marginal-LOC neurons, and a less populous, morphologically heterogeneous group, lying more distantly from the LSO, designated para-LOC neurons. Para-LOC neurons lying dorsal and rostral to LSO were significantly larger than marginal-LOC. We hypothesize that the cat marginal-LOC neurons and most probably the larger para-LOC neurons correspond to rodent intrinsic and shell LOC neurons, respectively, which have focal versus diffuse projections beneath the inner hair cells. Concerning MOC neurons, we confirm and extend previous observations on the clustering of these neurons near the rostral tip of the medial superior olivary nucleus and also show that MOC neurons differ in size according to cell group. Finally, we compare the present counts of OC neurons (mean total 1607, consisting of 1058 LOC neurons and 549 MOC neurons innervating one cochlea) and their proportional distribution ipsilaterally and contralaterally with those reported previously. Our estimate of the number of LOC neurons is somewhat higher than those previously obtained either by retrograde labeling with horseradish peroxidase or by counting unmyelinated axons in the olivocochlear bundle. In contrast, our estimate of the number of MOC neurons is very similar to those previously reported.

Calcium channels triggering transmitter release in the rat medial superior olive

We used whole cell voltage clamp recordings from neurones in rat auditory brainstem slices to study the Ca 2+ channel types involved in triggering synaptic glutamate and glycine release in the medial superior olivary nucleus. Glutamate release from the anterior ventral cochlear (aVCN) bushy neurone synapse did not involve L-type Ca 2+ channels (α 1C–D; Ca V1.2–1.3), but was mediated with similar efficacies by both N-type (α 1B; Ca V2.2) and the P/Q-type Ca 2+ channels (α 1A; Ca V2.1). Glycine release from the medial nucleus of the trapezoid body (MNTB) synapse was mediated predominantly by P/Q-type Ca 2+ channels, but with a significant contribution from N-type Ca 2+ channels. Combined application of the P/Q- and N-type Ca 2+ channel toxins, ω-agatoxin IVA and ω-conotoxin GVIA, left a very small remnant of both the inhibitory and excitatory postsynaptic currents, probably reflecting a minimal contribution of R-type Ca 2+ channels (α 1E; Ca V2.3) to transmitter release. In contrast with aVCN bushy neurones, MNTB somata lacked both T- (α 1G–I; Ca V3.1–3.3) and L-type channels, but expressed a higher proportion of P/Q-type Ca 2+ channels.

Development of brain-derived neurotrophic factor and neurotrophin-3 immunoreactivity in the lower auditory brainstem of the postnatal gerbil.

The localization of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the gerbil auditory brainstem was studied during normal postnatal development. The principal objective of this paper was to compare the developmental distribution of BDNF and NT-3 proteins to the known developmental distribution of their cognate, high-affinity tyrosine kinase receptors. BDNF and NT-3 proteins were localized using standard immunohistochemistry. No specific immunoreactivity for BDNF or NT-3 was detected on the day of birth (P0) in any auditory structure, although fibers comprising the spinal tract of the Vth cranial nerve were well labelled with antibodies against BDNF. Diffuse immunoreactivity for both BDNF and NT-3 was first detected at P3 in the cochlear nucleus and in several second order auditory nuclei in the superior olivary complex. This diffuse immunoreactivity became clustered and restricted to neuronal cell bodies by P10. Immunoreactivity for both BDNF and NT-3 transiently disappeared in the lateral and medial superior olivary nuclei at P10. However, neurons in the medial nucleus of the trapezoid body remained immunopositive for both BDNF and NT-3. Fibers in the trapezoid body were labelled with BDNF immunoreactivity by P12. Between P12 and P15, the distribution of BDNF and NT-3 immunoreactivity in the cochlear nucleus and superior olivary complex became comparable to adult (P140) immunolabel. These results show that the normal developmental distribution of the neurotrophins BDNF and NT-3 in the lower auditory brainstem occurs during the first two postnatal weeks in parallel with the developmental expression of their cognate receptors, trkB and trkC.

Conductive hearing loss results in changes in cytochrome oxidase activity in gerbil central auditory system.

Conductive hearing loss (CHL) restricts auditory input to an intact peripheral auditory system. Effects of deprivation on the central auditory system (CAS) have been debated, although a number of studies support the hypothesis that CHL can cause modification of CAS structure and function. The present study was designed to test the hypothesis that unilateral CHL results in a decrease in cytochrome oxidase (CO) activity in CAS nuclei that receive major afferent input from the affected ear. Gerbils at postnatal day 12 (P21) or 6-8 weeks underwent left unilateral CHL (malleus removal), cochlear ablation, or a sham surgical procedure. After a survival time of 48 hours or 3 weeks, animals were sacrificed and tissue was processed for cytochrome oxidase histochemistry. Optical density (OD) measurements were made from individual neurons in the anteroventral cochlear nucleus (AVCN) and from medial and lateral dendritic fields in the medial superior olivary nucleus (MSO), the lateral superior olivary nucleus, and the inferior colliculus. The width of the CO-stained neuropil in MSO was also measured as an estimate of dendritic length. OD measures were corrected to neutral areas of the brain. Cochlear ablation caused significant decreases in CO activity in left lower brainstem nuclei, particularly in adult animals. Following CHL, a significant decrease in CO activity was observed in the ipsilateral AVCN and a significant increase was observed in the contralateral AVCN. Cochlear ablation resulted in decreased width of MSO neuropil containing dendrites that receive primary input from the ablated ear. CHL resulted in a significant increase in the width of MSO neuropil on both sides of the brain in the P21 animals that survived 3 weeks but not in P21 animals that survived only 48 hours or in the adult animals. Unilateral CHL is associated with changes in CO activity in the AVCN and may affect MSO dendritic length in younger animals.