Medial Nucleus Of Trapezoid Body Research Articles

Electrical signaling in cochlear efferents is driven by an intrinsic neuronal oscillator

Efferent neurons are believed to play essential roles in maintaining auditory function. The lateral olivocochlear (LOC) neurons-which project from the brainstem to the inner ear, where they release multiple transmitters including peptides, catecholamines, and acetylcholine-are the most numerous yet least understood elements of efferent control of the cochlea. Using invitro calcium imaging and patch-clamp recordings, we found that LOC neurons in juvenile and young adult mice exhibited extremely slow waves of activity (∼0.1 Hz). These seconds-long bursts of Na+ spikes were driven by an intrinsic oscillator dependent on L-type Ca2+ channels and were not observed in prehearing mice, suggesting an age-dependent mechanism underlying the intrinsic oscillator. Using optogenetic approaches, we identified both ascending (T-stellate cells of the cochlear nucleus) and descending (auditory cortex) sources of synaptic excitation, as well as the synaptic receptors used for such excitation. Additionally, we identified potent inhibition originating in the glycinergic medial nucleus of trapezoid body (MNTB). Conductance-clamp experiments revealed an unusual mechanism of electrical signaling in LOC neurons, in which synaptic excitation and inhibition served to switch on and off the intrinsically generated spike burst mechanism, allowing for prolonged periods of activity or silence controlled by brief synaptic events. Protracted bursts of action potentials may be essential for effective exocytosis of the diverse transmitters released by LOC fibers in the cochlea.

Cytoarchitecture of the medial nucleus of trapezoid body of three neotropical species of bats (Noctilio leporinus, Phyllostomus hastatus, and Carollia perspicillata) with different foraging behavior

Abstract The present study was taken to test the hypothesis that the medial nucleus of the trapezoid body (MNTB) of echolocating neotropical bats with different foraging behavior will exhibit morphological variations in relative size, degree of complexity and spatial distribution. The brains were collected from six male adult bats of each species: Noctilio leporinus (fish-eating), Phyllostomus hastatus (carnivorous/ omnivorous) and Carollia perspicillata (fruit-eating) and were double-embedded and transverse serial sections were cut and stained with cresyl fast violet. The results showed that the MNTB is well developed in all the bats in general and the mean length of the MNTB was 1160 ± 124 µm in N. leporinus, 400 ± 59 µm in P. hastatus and 320 ± 25µm in C. perspicillata. The body and brain weight do not reflect proportionately on the size of the MNTB in the present study. The hearing frequency spectrum did not covary with the size of the MNTB among the bats studied. The MNTB is clearly demarcated from the ventral nucleus of the trapezoid body (VNTB) only in P. hastatus. The MNTB comprised mainly three types of cells in all three bats: dense-staining multipolar cells (12.5 µm and 25.0 µm diameter); light-staining multipolar cells measuring (12.5 µm and 25.0 µm diameter) and light-staining round cells (5.0 µm diameter). The large sized MNTB was observed in N. leporinus, which suggests that it relies heavily on echolocation whereas P. hastatus and C. perspicillata use echolocation as well but also rely on hearing, smell and vision.

Endogenous Cholinergic Signaling Modulates Sound-Evoked Responses of the Medial Nucleus of the Trapezoid Body.

The medial nucleus of trapezoid body (MNTB) is a major source of inhibition in auditory brainstem circuitry. The MNTB projects well-timed inhibitory output to principal sound-localization nuclei in the superior olive (SOC) as well as other computationally important centers. Acoustic information is conveyed to MNTB neurons through a single calyx of Held excitatory synapse arising from the cochlear nucleus. The encoding efficacy of this large synapse depends on its activity rate, which is primarily determined by sound intensity and stimulus frequency. However, MNTB activity rate is additionally influenced by inhibition and possibly neuromodulatory inputs, albeit their functional role is unclear. Happe and Morley (2004) discovered prominent expression of α7 nAChRs in rat SOC, suggesting possible engagement of ACh-mediated modulation of neural activity in the MNTB. However, the existence and nature of this putative modulation have never been physiologically demonstrated. We probed nicotinic cholinergic influences on acoustic responses of MNTB neurons from adult gerbils (Meriones unguiculatus) of either sex. We recorded tone-evoked MNTB single-neuron activity in vivo using extracellular single-unit recording. Piggyback multibarrel electrodes enabled pharmacological manipulation of nAChRs by reversibly applying antagonists to two receptor types, α7 and α4β2. We observed that tone-evoked responses are dependent on ACh modulation by both nAChR subtypes. Spontaneous activity was not affected by antagonist application. Functionally, we demonstrate that ACh contributes to sustaining high discharge rates and enhances signal encoding efficacy. Additionally, we report anatomic evidence revealing novel cholinergic projections to MNTB arising from pontine and superior olivary nuclei.SIGNIFICANCE STATEMENT This study is the first to physiologically probe how acetylcholine, a pervasive neuromodulator in the brain, influences the encoding of acoustic information by the medial nucleus of trapezoid body, the most prominent source of inhibition in brainstem sound-localization circuitry. We demonstrate that this cholinergic input enhances neural discrimination of tones from noise stimuli, which may contribute to processing important acoustic signals, such as speech. Additionally, we describe novel anatomic projections providing cholinergic input to the MNTB. Together, these findings shed new light on the contribution of neuromodulation to fundamental computational processes in auditory brainstem circuitry and to a more holistic understanding of modulatory influences in sensory processing.

Subtle differences in synaptic transmission in medial nucleus of trapezoid body neurons between wild-type and Fmr1 knockout mice

In animal models for fragile X syndrome where the gene for fragile X mental retardation protein is knocked out (Fmr1 KO), neurotransmission in multiple brain regions shifts excitation/inhibition balance, resulting in hyperexcitability in neural circuits. Here, using whole-cell recordings from brainstem slices, we investigated synaptic transmission at the medial nucleus of trapezoid body (MNTB, a critical nucleus in the brainstem sound localization circuit), in Fmr1 KO and wild-type (WT) mice 2–3 weeks of age in both sexes. Surprisingly, neither synaptic excitation nor inhibition in KO neurons was significantly changed. The synaptic strength, kinetics, and short-term plasticity of synaptic excitation remained largely unaltered. Subtle differences were observed in response patterns, with KO neurons displaying less all-or-none eEPSCs. Similarly, synaptic inhibition mediated by glycine and GABA remains largely unchanged, except for a slower kinetics of mixed sIPSCs. In pharmacologically isolated glycinergic and GABAergic inhibition, no significant differences in synaptic strength and kinetics were detected between the two genotypes. These results demonstrate that at the cellular level synaptic transmission at MNTB is largely unaffected in Fmr1 KO mice by 2–3 weeks after birth, suggesting the existence of compensatory mechanisms that maintain the inhibitory output of MNTB to its targets in the auditory brainstem.

Neuroanatomical characterization of perineuronal net components in the human cochlear nucleus and superior olivary complex

The human auditory brainstem, especially the cochlear nucleus (CN) and the superior olivary complex (SOC) are characterized by a high density of neurons associated with perineuronal nets (PNs). PNs build a specific form of extracellular matrix surrounding the neuronal somata, proximal dendrites and axon initial segments. They restrict synaptic plasticity and control high-frequency synaptic activity, a prominent characteristic of neurons of the auditory brainstem. The distribution of PNs within the auditory brainstem has been investigated in a number of mammalian species. However, much less is known regarding PNs in the human auditory brainstem. The present study aimed at the immunohistochemical identification of PNs in the cochlear nucleus (CN) and superior olivary complex (SOC) in the human brainstem. We focused on the complex nature and molecular variability of PNs in the CN and SOC by using specific antibodies against the main PN components (aggrecan, brevican, neurocan and hyaluronan and proteoglycan link protein 1). Virtually all subnuclei within the ventral CN and SOC were found to be associated with PNs. Direct comparison between gerbil and human yielded similar fine structure of PNs and confirmed the typical tight interdigitation of PNs with synaptic terminals in both species. Noticeably, an elaborate combination of immunohistochemical labelings clearly supports the still debated existence of the medial nucleus of trapezoid body (MNTB) in the human brain. In conclusion, the present study demonstrates that PNs form a prominent extracellular structure on CN and SOC neurons in the human brain, potentially stabilizing synaptic contacts, which is in agreement with many other mammalian species.

Mechanism of auditory hypersensitivity in human autism using autism model rats.

Auditory hypersensitivity is one of the major complications in autism spectrum disorder. The aim of this study was to investigate whether the auditory brain center is affected in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. In autism model rats, SOC immunoreactivity was markedly decreased. Strength of immunostaining of SOC auditory fibers was also weak in autism model rats. Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus exerting inhibitory function in SOC, was significantly decreased in autism model rats. Auditory hypersensitivity may be, in part, due to impairment of inhibitory processing by the auditory brain center.

Differential morphology of the superior olivary complex of Meriones unguiculatus and Monodelphis domestica revealed by calcium-binding proteins.

In mammals, the superior olivary complex (SOC) of the brainstem is composed of nuclei that integrate afferent auditory originating from both ears. Here, the expression of different calcium-binding proteins in subnuclei of the SOC was studied in distantly related mammals, the Mongolian gerbil (Meriones unguiculatus) and the gray short-tailed opossum (Monodelphis domestica) to get a better understanding of the basal nuclear organization of the SOC. Combined immunofluorescence labeling of the calcium-binding proteins (CaBPs) parvalbumin, calbindin-D28k, and calretinin as well as pan-neuronal markers displayed characteristic distribution patterns highlighting details of neuronal architecture of SOC nuclei. Parvalbumin was found in almost all neurons of SOC nuclei in both species, while calbindin and calretinin were restricted to specific cell types and axonal terminal fields. In both species, calbindin displayed a ubiquitous and mostly selective distribution in neurons of the medial nucleus of trapezoid body (MNTB) including their terminal axonal fields in different SOC targets. In Meriones, calretinin and calbindin showed non-overlapping expression patterns in neuron somata and terminal fields throughout the SOC. In Monodelphis, co-expression of calbindin and calretinin was observed in the MNTB, and hence both CaBPs were also co-localized in terminal fields within the adjacent SOC nuclei. The distribution patterns of CaBPs in both species are discussed with respect to the intrinsic neuronal SOC circuits as part of the auditory brainstem system that underlie the binaural integrative processing of acoustic signals as the basis for localization and discrimination of auditory objects.

Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons.

BackgroundIn the auditory brainstem, ventral cochlear nucleus (VCN) axons project to the contralateral, but not ipsilateral, medial nucleus of trapezoid body (MNTB), terminating in the calyx of Held. Dorsal VCN neurons, representing high frequencies, synapse with medial MNTB neurons, while low frequency-coding ventral VCN neurons synapse with lateral MNTB neurons, reflecting tonotopic organization. The mechanisms that ensure strictly contralateral targeting and topographic ordering are incompletely understood. Here we examined the roles of ephrin-A signaling in both types of targeting.ResultsEphrin-A2 and ephrin-A5 are expressed in VCN cells during late embryonic and early postnatal development. At these ages ephrin-A2 is expressed in axons surrounding MNTB and ephrin-A5 is expressed in MNTB principal neurons. Ephrin-A2/A5 double knockout mice displayed axon targeting errors in which VCN axons project to MNTB on both sides of the brainstem, where they terminate in calyceal endings. Ephrin-A2 and ephrin-A5 single knockout mice showed a similar phenotype. In contrast to effects on contralateral targeting, ephrin-A2/A5 double knockout mice showed no defects in formation of tonotopically ordered projections from VCN to MNTB.ConclusionsThese findings demonstrate that distinct mechanisms regulate targeting of VCN axons to the contralateral MNTB and targeting to appropriate tonotopic locations. Ephrin-A signaling plays a similar role to ephrin-B signaling in the VCN-MNTB pathway, where both classes normally prevent formation of calyceal projections to ipsilateral MNTB. These classes may rely in part on common signaling pathways.

Developmental profiles of the intrinsic properties and synaptic function of auditory neurons in preterm and term baboon neonates.

The human fetus starts to hear and undergoes major developmental changes in the auditory system during the third trimester of pregnancy. Although there are significant data regarding development of the auditory system in rodents, changes in intrinsic properties and synaptic function of auditory neurons in developing primate brain at hearing onset are poorly understood. We performed whole-cell patch-clamp recordings of principal neurons in the medial nucleus of trapezoid body (MNTB) in preterm and term baboon brainstem slices to study the structural and functional maturation of auditory synapses. Each MNTB principal neuron received an excitatory input from a single calyx of Held terminal, and this one-to-one pattern of innervation was already formed in preterm baboons delivered at 67% of normal gestation. There was no difference in frequency or amplitude of spontaneous excitatory postsynaptic synaptic currents between preterm and term MNTB neurons. In contrast, the frequency of spontaneous GABA(A)/glycine receptor-mediated inhibitory postsynaptic synaptic currents, which were prevalent in preterm MNTB neurons, was significantly reduced in term MNTB neurons. Preterm MNTB neurons had a higher input resistance than term neurons and fired in bursts, whereas term MNTB neurons fired a single action potential in response to suprathreshold current injection. The maturation of intrinsic properties and dominance of excitatory inputs in the primate MNTB allow it to take on its mature role as a fast and reliable relay synapse.

Differential Distribution of Glycine Receptor Subtypes at the Rat Calyx of Held Synapse

The properties of glycine receptors (GlyRs) depend upon their subunit composition. While the prevalent adult forms of GlyRs are heteromers, previous reports suggested functional α homomeric receptors in mature nervous tissues. Here we show two functionally different GlyRs populations in the rat medial nucleus of trapezoid body (MNTB). Postsynaptic receptors formed α1/β-containing clusters on somatodendritic domains of MNTB principal neurons, colocalizing with glycinergic nerve endings to mediate fast, phasic IPSCs. In contrast, presynaptic receptors on glutamatergic calyx of Held terminals were composed of dispersed, homomeric α1 receptors. Interestingly, the parent cell bodies of the calyces of Held, the globular bushy cells of the cochlear nucleus, expressed somatodendritic receptors (α1/β heteromers) and showed similar clustering and pharmacological profile as GlyRs on MNTB principal cells. These results suggest that specific targeting of GlyR β-subunit produces segregation of GlyR subtypes involved in two different mechanisms of modulation of synaptic strength.

Unique features of extracellular matrix in the mouse medial nucleus of trapezoid body – Implications for physiological functions

The medial nucleus of the trapezoid body (MNTB) is a vital structure of sound localization circuits in the auditory brainstem. Each principal cell of MNTB is contacted by a very large presynaptic glutamatergic terminal, the calyx of Held. The MNTB principal cells themselves are surrounded by extracellular matrix components forming prominent perineuronal nets (PNs). Throughout the CNS, PNs, which form lattice-like structures around the somata and proximal dendrites, are associated with distinct types of neurons. PNs are highly enriched in hyaluronan and chondroitin sulfate proteoglycans therefore providing a charged surface structure surrounding the cell body and proximal neurites of these neurons. The localization and composition of PNs have lead investigators to a number of hypotheses about their functions including: creating a specific extracellular ionic milieu around these neurons, stabilizing synapses, and influencing the outgrowth of axons. However, presently the precise functions of PNs are still quite unclear primarily due to the lack of an ideal experimental model system that is highly enriched in PNs and in which the synaptic transmission properties can be precisely measured. The MNTB principal cells could offer such a model, since they have been extensively characterized electrophysiologically. However, extracellular matrix (ECM) in these neurons has not yet been precisely detailed. The present study gives a detailed examination of the ECM organization and structural differences in PNs of the mouse MNTB. The different PN components and their distribution pattern are scrutinized throughout the MNTB. The data are complemented by electron microscopic investigations of the unique ultrastructural localization of PN-components and their interrelation with distinct pre- and postsynaptic MNTB cell structures. Therefore, we believe this work identifies the MNTB as an ideal system for studying PN function.

Long term depression of MNTB-LSO synapses is expressed postsynaptically in developing circling mice

Early onset long term depression (LTD) during the first postnatal week has rarely been demonstrated at the medial nucleus of trapezoid body (MNTB) – lateral superior olive (LSO) synapses in spite of many favorable conditions, such as depolarizing synapses and glutamate co-release from MNTB terminals. Thus, we tested the early expression of LTD at MNTB-LSO synapses during the first postnatal week using circling mice, whose main transmitter is glutamate at MNTB-LSO synapses. Tetanic stimulation on MNTB elicited LTD of postsynaptic currents recorded at LSO neurons in P0–P3 homozygous (cir/cir) mice (45.8±0.3% of the control, n=7) and heterozygous (+/cir) mice (43.3±0.4% of the control, n=7). The magnitude of LTD decreased in P8–P12 heterozygous (+/cir) mice (84.5±0.3% of the control, n=7), but was maintained in P8–P12 homozygous (cir/cir) mice (38.2±0.3% of the control, n=9). Glutamatergic LTD observed in homozygous (cir/cir) mice and glycinergic LTD observed heterozygous (+/cir) mice showed similar pattern of change. As currents induced by the pressure application of glycine on LSO neurons were reduced by tetanic stimulation in P0–P3 heterozygous (+/cir) mice, LTD was thought to occur at postsynaptic sites. Our results suggest that LTD might occur in vivo and participate in the synaptic silencing and strengthening of MNTB-LSO synapses, which is most active during the first postnatal week.

Modelling homeostatic control of intrinsic excitability in single neurons

Event Abstract Back to Event Modelling homeostatic control of intrinsic excitability in single neurons Yann Sweeney1, 2* and Matthias Hennig1 1 University of Edinburgh, School of Informatics, United Kingdom 2 KTH Royal Institute of Technology, Department of Computational Biology, Sweden Intrinsic excitability in neurons is controlled by a number of homeostatic mechanisms, among which are the modulation of conductances in voltage-dependent ion channels and the modulation of the distance of the axon initial segment (AIS) from the soma. Due to their large size and good accessibility in slice experiments, a useful model system for these forms of homeostatic regulation are principal neurons of the medial nucleus of trapezoid body (MNTB) in the auditory brainstem. These act as relay neurons, receiving excitatory input and transmitting inhibitory signals to the auditory nuclei involved in sound localisation. One form of homeostasis of intrinsic excitability has been shown to be mediated by Nitric Oxide (NO), which is released by MNTB neurons in an activity-dependent manner and modulates Kv3 and Kv2 potassium channels conductance. We have investigated this homeostatic regulation in a multi-compartment MNTB neuron model, incorporating the localisation of ion channels in the soma and the AIS. The analysis of the model showed that the main effects of NO synthesis, a reduction of excitability and concomitant changes in action potential shape as observed in vitro (Steinert et al., Neuron, 2008, 2011), can be accounted for by increasing Kv2 conductances. Moreover, we found that the localisation of ion channels in the AIS, as opposed to the soma, results in a significantly faster action potential onset, with this effect increasing as the AIS is located more distally to the soma. Consistent with previous reports (Grubb & Burrone, Nature, 2010), the latter also increased neural excitability. We currently investigate how NO synthesis and AIS location affect the integration of synaptic inputs for different average activity levels and other statistical features of the input. Acknowledgements MRC Fellowship G0900425 EuroSPIN EMJD Fellowship EPSRC and BBSRC funded Doctoral Training Centre programme at School of Informatics, University of Edinburgh References [Steinert et al., 2008] Steinert, J. R., Kopp-Scheinpflug, C., Baker, C., Challiss, R. a J., Mistry, R., Haustein, M. D., Griffin, S. J., et al. (2008). Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse. Neuron, 60(4), 642-56. Elsevier Inc. doi:10.1016/j.neuron.2008.08.025 [Steinert et al., 2011] Steinert, J. R., Robinson, S. W., Tong, H., Haustein, M. D., Kopp-Scheinpflug, C., & Forsythe, I. D. (2011). Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability. Neuron, 71(2), 291-305. Elsevier Inc. doi:10.1016/j.neuron.2011.05.037 [Grubb & Burrone, 2010] Grubb, M. S., & Burrone, J. (2010). Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature, 465(7301), 1070-4. Nature Publishing Group. doi:10.1038/nature09160 Keywords: axon initial segment, Compartmental neuron model, Homeostasis, Ion Channels, MNTB, Nitric Oxide Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012. Presentation Type: Poster Topic: Other Citation: Sweeney Y and Hennig M (2012). Modelling homeostatic control of intrinsic excitability in single neurons. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00239 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Sep 2012; Published Online: 12 Sep 2012. * Correspondence: Mr. Yann Sweeney, University of Edinburgh, School of Informatics, Edinburgh, Edinburgh, EH8 9AB, United Kingdom, yann.sweeney@ed.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yann Sweeney Matthias Hennig Google Yann Sweeney Matthias Hennig Google Scholar Yann Sweeney Matthias Hennig PubMed Yann Sweeney Matthias Hennig Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

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.

Developmental changes in calcium channel types mediating synaptic transmission in rat auditory brainstem.

1. Calcium channel blockers were tested on excitatory postsynaptic currents (EPSCs) at the synapse formed by the calyx of Held on the principal cells in the medial nucleus of trapezoid body (MNTB) in brainstem slices of 4- to 14-day-old rats. 2. At postnatal day 4-9 (P4-9), EPSCs were irreversibly suppressed by the P/Q-type Ca2+ channel blocker omega-agatoxin-IVA (omega-Aga-IVA, 200 nM) and also by the N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTx, 2 microM). A small fraction of EPSCs was resistant to both toxins but abolished by Cd2+ (100 microM). 3. After P7, the omega-CgTx-sensitive EPSC fraction diminished and eventually disappeared after P10. Concomitantly the fraction insensitive to both toxins decreased and became undetectable after P10. 4. In contrast, the omega-Aga-IVA-sensitive EPSC fraction increased with development and became predominant after P10. All through the developmental period examined, the L-type Ca2+ channel blocker nicardipine (10 microM) had no effect. 5. We conclude that presynaptic Ca2+ channel types triggering transmitter release undergo developmental switching during the early postnatal period.

Input from the medial nucleus of trapezoid body to an interaural level detector

The medial nucleus of the trapezoid body (MNTB) contains components of a neural network that functions as an interaural level difference (ILD) detector. In the cat, lateral superior olivary (LSO) neurons compare the contralateral inhibitory input from the MNTB with an excitatory input from the ipsilateral anteroventral cochlear nucleus to extract information about binaural stimuli. To better specify the inhibitory inputs to the LSO and gain a better understanding of the inhibitory component of the LSO network, the response characteristics of MNTB neurons were examined in cats under stimulus conditions similar to those used to study LSO inhibitory responses. The inhibitory tuning curves of LSO units were wider than the tuning curves of MNTB units. Hence, MNTB neurons with similar, but not identical, characteristic frequencies converge to provide inhibitory input to single LSO neurons. Variations in the number of converging MNTB inputs produced a range of LSO excitatory-inhibitory threshold differences, thus creating a coding mechanism for representing the ILD. Convergence of MNTB inputs also increased the dynamic range over which contralateral stimulus level effects LSO binaural responses beyond the dynamic ranges of individual MNTB units, thus expanding the ILD range encoded by the LSO network. The differences between the first-spike latencies of MNTB and LSO tone burst responses were small and the precision of the LSO first-spike discharges was significantly greater than that of MNTB units. As tone bursts delivered simultaneously to the two ears can consistently inhibit LSO first-spike discharges, the inhibitory input must match the LSO precision by converging a number of the more variably timed MNTB discharges. Because of their precision LSO first-spike discharges may be used to encode interaural time-of-arrival differences of mid- to high-frequency transients. These findings add to the foundation for a comprehensive network model that describes the inputs to the LSO as point processes, delimits the biophysical mechanisms underlying excitatory and inhibitory interactions at the single neuron level, and reveals how these inputs determine the response to different binaural stimulus conditions.

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.

Brainstem location of efferent neurones projecting to the guinea pig cochlea

Retrograde transport of horseradish peroxidase using tetramethylbenzidine as a chromagen was used to map the cell bodies of origin of the efferent projection to the cochlea in the guinea pig. Large numbers of small labelled neurones were found within the body of the lateral superior olivary nucleus (LSO) ipsi-lateral to the injected cochlea. Labelled cells within the contra-lateral LSO were extremely rare (1% or less). Large labelled neurones were found both ipsi-laterally and contra-laterally in the dorsomedial periolivary region, including the medial nucleus of trapezoid body and in the ventral and lateral nuclei of the trapezoid body and the ventral nucleus of lateral lemniscus. It was concluded that some aspects of the distribution of these efferent neurones in the guinea pig are similar to the situation in the rat, whilst others resemble more closely the arrangement found in cat.

Late onset of auditory deprivation does not affect brainstem auditory neuron soma size.

Neuronal soma sizes from normal mice, mice with conductive losses from 45 days, and avocal mice subjected to sound deprivation from 45 days, were studied at 90 days, revealing no significant differences between groups for cochlear nuclear globular cells, or cells of medial nucleus of trapezoid body or inferior colliculus.