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Albert S Berrebi - One of the best experts on this subject based on the ideXlab platform.
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forward masking in the medial nucleus of the Trapezoid Body of the rat
Brain Structure & Function, 2016Co-Authors: Albert S BerrebiAbstract:Perception of acoustic stimuli is modulated by the temporal and spectral relationship between sound components. Forward masking experiments show that the perception threshold for a probe tone is significantly impaired by a preceding masker stimulus. Forward masking has been systematically studied at the level of the auditory nerve, cochlear nucleus, inferior colliculus and auditory cortex, but not yet in the superior olivary complex. The medial nucleus of the Trapezoid Body (MNTB), a principal cell group of the superior olive, plays an essential role in sound localization. The MNTB receives excitatory input from the contralateral cochlear nucleus via the calyces of Held and innervates the ipsilateral lateral and medial superior olives, as well as the superior paraolivary nucleus. Here, we performed single-unit extracellular recordings in the MNTB of rats. Using a forward masking paradigm previously employed in studies of the inferior colliculus and auditory nerve, we determined response thresholds for a 20-ms characteristic frequency pure tone (the probe), and then presented it in conjunction with another tone (the masker) that was varied in intensity, duration, and frequency; we also systematically varied the masker-to-probe delay. Probe response thresholds increased and response magnitudes decreased when a masker was presented. The forward suppression effects were greater when masker level and masker duration were increased, when the masker frequency approached the MNTB unit’s characteristic frequency, and as the masker-to-probe delay was shortened. Probe threshold shifts showed an exponential decay as the masker-to-probe delay increased.
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encoding of temporal features of auditory stimuli in the medial nucleus of the Trapezoid Body and superior paraolivary nucleus of the rat
Neuroscience, 2008Co-Authors: Alexander Kadner, Albert S BerrebiAbstract:Abstract Neurons in the superior paraolivary nucleus (SPON) of the rat respond to the offset of pure tones with a brief burst of spikes. Medial nucleus of the Trapezoid Body (MNTB) neurons, which inhibit the SPON, produce a sustained pure tone response followed by an offset response characterized by a period of suppressed spontaneous activity. This MNTB offset response is duration dependent and critical to the formation of SPON offset spikes [Kadner A, Kulesza RJ Jr, Berrebi AS (2006) Neurons in the medial nucleus of the Trapezoid Body and superior paraolivary nucleus of the rat may play a role in sound duration coding. J Neurophysiol. 95:1499–1508; Kulesza RJ Jr, Kadner A, Berrebi AS (2007) Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 97:1610–1620]. Here we examine the temporal resolution of the rat's MNTB/SPON circuit by assessing its capability to i ) detect gaps in tones, and ii ) synchronize to sinusoidally amplitude modulated (SAM) tones. Gap detection was tested by presenting two identical pure tone markers interrupted by gaps ranging from 0 to 25 ms duration. SPON neurons responded to the offset of the leading marker even when the two markers were separated only by their ramps (i.e. a 0 ms gap); longer gap durations elicited progressively larger responses. MNTB neurons produced an offset response at gap durations of 2 ms or longer, with a subset of neurons responding to 0 ms gaps. SAM tone stimuli used the unit's characteristic frequency as a carrier, and modulation rates ranged from 40 to 1160 Hz. MNTB neurons synchronized to modulation rates up to ∼1 kHz, whereas spiking of SPON neurons decreased sharply at modulation rates ≥400 Hz. Modulation transfer functions based on spike count were all-pass for MNTB neurons and low-pass for SPON neurons; the modulation transfer functions based on vector strength were low-pass for both nuclei, with a steeper cutoff for SPON neurons. Thus, the MNTB/SPON circuit encodes episodes of low stimulus energy, such as gaps in pure tones and troughs in amplitude modulated tones. The output of this circuit consists of brief SPON spiking episodes; their potential effects on the auditory midbrain and forebrain are discussed.
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neurons in the medial nucleus of the Trapezoid Body and superior paraolivary nucleus of the rat may play a role in sound duration coding
Journal of Neurophysiology, 2006Co-Authors: Alexander Kadner, Randy J Kulesza, Albert S BerrebiAbstract:We describe neurons in two nuclei of the superior olivary complex that display differential sensitivities to sound duration. Single units in the medial nucleus of the Trapezoid Body (MNTB) and supe...
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ultrastructure of neurons and large synaptic terminals in the lateral nucleus of the Trapezoid Body of the cat
The Journal of Comparative Neurology, 1998Co-Authors: George A Spirou, Kevin C Rowland, Albert S BerrebiAbstract:Neurons of the lateral nucleus of the Trapezoid Body (LNTB), the most prominent periolivary nucleus of the cat superior olivary complex, form an important component of the descending auditory pathways and also innervate the medial superior olive. Cells forming the posteroventral subnucleus (pvLNTB), when investigated by light microscopy, exhibit morphological similarities with globular bushy cells of the cochlear nucleus and principal cells of the medial nucleus of the Trapezoid Body. These latter two cell types are integral components of brainstem circuitry mediating the early stages of sound localization. In this report, ultrastructural features of LNTB neurons are described. pvLNTB cell bodies are characterized by a round to oval shape, smooth nuclear membrane, and the relative paucity of stacks of rough endoplasmic reticulum. In addition, pvLNTB cell bodies and proximal dendrites are contacted by large synaptic terminals which contain round synaptic vesicles and form multiple asymmetric synaptic junctions. These ultrastructural characteristics are similar to those previously described for globular and principal cells and distinguish pvLNTB cells from cells of the main subnucleus. Large terminals contacting pvLNTB cells contain a specialized organelle assembly, including an adherens plaque associated by filamentous strands with a mitochondrion. We name this organelle assembly the mitochondria-associated adherens complex (MAC) and note its proximity to synaptic junctions. Because high activity rates are characteristic of large terminals in the lower auditory system, the MAC may play a specialized role in membrane stabilization at synapses which generate high rates of vesicle membrane turnover. J. Comp. Neurol. 398:257–272, 1998. © 1998 Wiley-Liss, Inc.
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glycine immunoreactivity in the lateral nucleus of the Trapezoid Body of the cat
The Journal of Comparative Neurology, 1997Co-Authors: George A Spirou, Albert S BerrebiAbstract:The central auditory system contains several predominantly glycine-immunoreactive nuclei, and one of these, the lateral nucleus of the Trapezoid Body, contains cell bodies exhibiting a spectrum of labeling intensity. By using post-embedding glycine immunocytochemistry on thin sections, and toluidine blue staining of adjacent sections, we established that darkly glycine-immunoreactive neurons constituted a distinct morphological class and form one of three subnuclei of the lateral nucleus of the Trapezoid Body, called the posteroventral subnucleus. These neurons resemble, in both labeling intensity and cell Body morphology, the principal cells of the medial nucleus of the Trapezoid Body. The other two subnuclei of the lateral nucleus of the Trapezoid Body, its main and hilus subnuclei, contained predominantly glycine-immunoreactive and glycine-immunonegative neurons, respectively. Glycine immunoreactivity was compared with γ-aminobutyric acid (GABA) immunoreactivity in order to identify other organizational features of the lateral nucleus of the Trapezoid Body. Cell bodies that displayed either dark glycine-immunoreactivity or which were glycine-immunonegative were GABA-immunonegative. Cell bodies that displayed GABA immunoreactivity were preferentially located in the main subnucleus. Patterns of distribution of axosomatic innervation in the lateral nucleus of the Trapezoid Body were revealed in which glycine-immunoreactive puncta were (1) more numerous than GABA-immunoreactive puncta on glycine-immunonegative cell bodies and (2) equal to or less numerous than GABA-immunoreactive puncta on glycine-immunoreactive cell bodies. The characteristics of neural circuitry revealed by glycine and GABA immunoreactivity in the lateral nucleus of the Trapezoid Body may be generalizable to other populations of neurons of the superior olivary complex and to other regions of the central nervous system containing glycinergic neurons, such as the retina. J. Comp. Neurol. 383:473-488, 1997. © 1997 Wiley-Liss, Inc.
Ian D Forsythe - One of the best experts on this subject based on the ideXlab platform.
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strain specific differences in the development of neuronal excitability in the mouse ventral nucleus of the Trapezoid Body
Hearing Research, 2017Co-Authors: James L Sinclair, Conny Koppscheinpflug, Margaret Barnesdavies, Ian D ForsytheAbstract:Abstract This investigation compared the development of neuronal excitability in the ventral nucleus of the Trapezoid Body (VNTB) between two strains of mice with differing progression rates for age-related hearing loss. In contrast to CBA/Ca (CBA) mice, the C57BL/6J (C57) strain are subject to hearing loss from a younger age and are more prone to damage from sound over-exposure. Higher firing rates in the medial olivocochlear system (MOC) are associated with protection from loud sounds and these cells are located in the VNTB. We postulated that reduced neuronal firing of the MOC in C57 mice could contribute to hearing loss in this strain by reducing efferent protection. Whole cell patch clamp was used to compare the electrical properties of VNTB neurons from the two strains initially in two age groups: before and after hearing onset at ∼ P9 and ∼P16, respectively. Prior to hearing onset VNTB neurons electrophysiological properties were identical in both strains, but started to diverge after hearing onset. One week after hearing onset VNTB neurons of C57 mice had larger amplitude action potentials but in contrast to CBA mice, their waveform failed to accelerate with increasing age, consistent with the faster inactivation of voltage-gated potassium currents in C57 VNTB neurons. The lower frequency action potential firing of C57 VNTB neurons at P16 was maintained to P28, indicating that this change was not a developmental delay. We conclude that C57 VNTB neurons fire at lower frequencies than in the CBA strain, supporting the hypothesis that reduced MOC firing could contribute to the greater hearing loss of the C57 strain.
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regulation of kv channel expression and neuronal excitability in rat medial nucleus of the Trapezoid Body maintained in organotypic culture
The Journal of Physiology, 2010Co-Authors: Huaxia Tong, Susan W. Robinson, Tatyana Chernova, David J. Read, Douglas L. Oliver, Joern R Steinert, Ian D ForsytheAbstract:Principal neurons of the medial nucleus of the Trapezoid Body (MNTB) express a spectrum of voltage-dependent K+ conductances mediated by Kv1–Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9–P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K+]o medium. Whole cell patch-clamp recordings were made after 7–28 days in vitro. MNTB neurons cultured in high-K medium maintained a single AP firing phenotype, while low-K cultures had smaller K+ currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx-free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high-K aCSF only transiently increased spontaneous AP firing (<2 min) and did not measurably increase synaptic activity. Chronic depolarization in high-K cultures raised basal levels of [Ca2+]i, increased Kv3 currents and shortened AP half-widths. These events relied on raised [Ca2+]i, mediated by influx through voltage-gated calcium channels (VGCCs) and release from intracellular stores, causing an increase in cAMP-response element binding protein (CREB) phosphorylation. Block of VGCCs or of CREB function suppressed Kv3 currents, increased AP duration, and reduced Kv3.3 and c-fos expression. Real-time PCR revealed higher Kv3.3 and Kv1.1 mRNA in high-K compared to low-K cultures, although the increased Kv1.1 mRNA was mediated by a CREB-independent mechanism. We conclude that Kv channel expression and hence the intrinsic membrane properties of MNTB neurons are homeostatically regulated by [Ca2+]i-dependent mechanisms and influenced by sustained depolarization of the resting membrane potential.
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Regulation of Kv channel expression and neuronal excitability in rat medial nucleus of the Trapezoid Body maintained in organotypic culture
Scopus, 2010Co-Authors: Huaxia Tong, Steinert, Susan W. Robinson, Tatyana Chernova, David J. Read, Douglas L. Oliver, Ian D ForsytheAbstract:Principal neurons of the medial nucleus of the Trapezoid Body (MNTB) express a spectrum of voltage-dependent K(+) conductances mediated by Kv1-Kv4 channels, which shape action potential (AP) firing and regulate intrinsic excitability. Postsynaptic factors influencing expression of Kv channels were explored using organotypic cultures of brainstem prepared from P9-P12 rats and maintained in either low (5 mm, low-K) or high (25 mm, high-K) [K(+)](o) medium. Whole cell patch-clamp recordings were made after 7-28 days in vitro. MNTB neurons cultured in high-K medium maintained a single AP firing phenotype, while low-K cultures had smaller K(+) currents, enhanced excitability and fired multiple APs. The calyx of Held inputs degenerated within 3 days in culture, having lost their major afferent input; this preparation of calyx-free MNTB neurons allowed the effects of postsynaptic depolarisation to be studied with minimal synaptic activity. The depolarization caused by the high-K aCSF only transiently increased spontaneous AP firing (
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initial segment kv2 2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the Trapezoid Body neurons
The Journal of Physiology, 2008Co-Authors: Jamie Johnston, Sarah J Griffin, Claire A Baker, Anna E Skrzypiec, Tatanya Chernova, Ian D ForsytheAbstract:The medial nucleus of the Trapezoid Body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K+ current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of ∼37 nS; it is half-activated at −9.2 ± 2.1 mV and half-inactivated at −35.9 ± 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 μm) and high concentrations of extracellular tetraethylammonium (TEA; IC50= 11.8 mm), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antiBody showed specific staining and Western blots confirmed that it recognized a protein ∼110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin–Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing.
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systematic variation of potassium current amplitudes across the tonotopic axis of the rat medial nucleus of the Trapezoid Body
Hearing Research, 2005Co-Authors: Helen M Brew, Ian D ForsytheAbstract:Abstract Many central auditory nuclei preserve the tonotopic organization of their afferent inputs, generating a frequency “map” across the nucleus. In the medial nucleus of the Trapezoid Body (MNTB) the most medial neurons receive inputs corresponding to the highest frequency sounds and the most lateral neurons have the lowest characteristic frequencies. Whole-cell patch recording from MNTB principal neurons in rat brainstem slices demonstrates a corresponding tonotopic organization of voltage-gated outward potassium currents. Medial MNTB neurons had larger total outward K+ current amplitudes than lateral neurons and similar medial to-lateral gradients were observed for two K+ current subtypes distinguished by their low and high voltage activation thresholds. In contrast, a third K+ conductance with an intermediate voltage threshold and slower kinetics showed an inverse gradient (being smallest in medial MNTB). The orthogonal axes of MNTB did not exhibit potassium current gradients (dorsal-to-ventral, or rostral-to-caudal). The input resistance was unchanged across the MNTB, but a slow capacitative component was enhanced in lateral neurons. These data demonstrate that the intrinsic properties of rat MNTB neurons are tuned across the tonotopic axis so as to promote shorter action potentials, faster firing and therefore greater accuracy in transmission of auditory information in the high characteristic frequency regions.
Eckhard Friauf - One of the best experts on this subject based on the ideXlab platform.
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Developmental distribution of the glutamate receptor subunits KA2,GluR6/7, and δ1/2 in the rat medial nucleus of the Trapezoid Body
Cell and Tissue Research, 2002Co-Authors: Stefan Lohrke, Eckhard FriaufAbstract:The medial nucleus of the Trapezoid Body (MNTB) acts as a relay nucleus in the transmission of auditory information from the cochlear nucleus (CN) to the lateral superior olive. Glutamate receptors mediate the excitatory synaptic transmission in the CN-MNTB projection. Here, we used immunohistochemistry to investigate the expression pattern of the kainate receptor subunits KA2 and GluR6/7 and the orphan glutamate receptor subunits δ1/2 in principal neurons of the rat MNTB during early postnatal development (P2–59). To objectively quantify the intensity of immunoreactivity, images were scanned with a CCD camera and used for gray-value measurements. At all ages analyzed, each of the three antisera produced immunoreactivity in the somata of MNTB principal cells and in the neuropil. KA2 immunoreactivity of somata and neuropil remained nearly constant between P2 and 23. In contrast, the intensity of GluR6/7 immunoreactivity of somata and neuropil increased between P2 and 6, followed by a decrease until P10. Between P10 and 23, GluR6/7 immunoreactivity of neuropil remained nearly constant, whereas it increased in the somata. In both somata and neuropil, the intensity of δ1/2 immunoreactivity decreased between P2 and 10, reaching a constant, low level by P10. Our results demonstrate the continuous presence of the glutamate receptor subunits KA2, GluR6/7 and δ1/2 in the developing MNTB, yet quantitative changes occur which may be associated with functional differences.
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developmental distribution of the glutamate receptor subunits ka2 glur6 7 and δ1 2 in the rat medial nucleus of the Trapezoid Body
Cell and Tissue Research, 2002Co-Authors: Stefan Lohrke, Eckhard FriaufAbstract:The medial nucleus of the Trapezoid Body (MNTB) acts as a relay nucleus in the transmission of auditory information from the cochlear nucleus (CN) to the lateral superior olive. Glutamate receptors mediate the excitatory synaptic transmission in the CN-MNTB projection. Here, we used immunohistochemistry to investigate the expression pattern of the kainate receptor subunits KA2 and GluR6/7 and the orphan glutamate receptor subunits δ1/2 in principal neurons of the rat MNTB during early postnatal development (P2–59). To objectively quantify the intensity of immunoreactivity, images were scanned with a CCD camera and used for gray-value measurements. At all ages analyzed, each of the three antisera produced immunoreactivity in the somata of MNTB principal cells and in the neuropil. KA2 immunoreactivity of somata and neuropil remained nearly constant between P2 and 23. In contrast, the intensity of GluR6/7 immunoreactivity of somata and neuropil increased between P2 and 6, followed by a decrease until P10. Between P10 and 23, GluR6/7 immunoreactivity of neuropil remained nearly constant, whereas it increased in the somata. In both somata and neuropil, the intensity of δ1/2 immunoreactivity decreased between P2 and 10, reaching a constant, low level by P10. Our results demonstrate the continuous presence of the glutamate receptor subunits KA2, GluR6/7 and δ1/2 in the developing MNTB, yet quantitative changes occur which may be associated with functional differences.
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electrical membrane properties of Trapezoid Body neurons in the rat auditory brain stem are preserved in organotypic slice cultures
Journal of Neurobiology, 1998Co-Authors: Stefan Lohrke, Martin Kungel, Eckhard FriaufAbstract:The medial nucleus of the Trapezoid Body (MNTB) is a conspicuous structure in the mammalian auditory brain stem. It is a major component of the superior olivary complex and is involved in sound localization. Recently, organotypic slice culture preparations of the superior olivary complex were introduced to investigate the development of inhibitory and excitatory projections (Sanes and Hafidi, 1996; Lohmann et al., 1998). In the present article, we further assessed the organotypicity of our culture system (Lohmann et al., 1998) and examined electrical membrane properties of MNTB neurons expressed under culture conditions. To do so, MNTB neurons from early postnatal rats (P3–5) were studied after 3–6 days in vitro (DIV) by whole-cell patch-clamp recordings. Their mean resting potential was −59 mV, the input resistance averaged 171 MΩ, and the average time constant was 3 ms. Four types of voltage-activated conductances were observed in voltage-clamp recordings. All cells expressed a tetrodotoxin (TTX)-sensitive sodium current. Two types of potassium currents could be characterized: a tetraethylammonium (TEA)-sensitive and a 4-aminopyridine (4-AP)-sensitive conductance, both of which are composed of a transient and a sustained component. Finally, an inwardly rectifying current, activated by hyperpolarizing voltage steps, was found. In current-clamp recordings, depolarizing current pulses typically elicited a single action potential. In the presence of 4-AP, however, these current pulses induced a train of action potentials. The duration of action potentials was increased by 4-AP and the afterhyperpolarization was reduced. Hyperpolarizing current injections induced a “sag” in the membrane potential, indicating the influence of an inwardly rectifying current. Our results demonstrate that MNTB neurons in slice cultures have electrical membrane properties comparable to those of their counterparts in acute slices. © 1998 John Wiley & Sons, Inc. J Neurobiol 36: 395–409, 1998
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principal cells of the rat medial nucleus of the Trapezoid Body an intracellular in vivo study of their physiology and morphology
Experimental Brain Research, 1993Co-Authors: Inken Sommer, Kurt Lingenhohl, Eckhard FriaufAbstract:The medial nucleus of the Trapezoid Body (MNTB) is one of several principal nuclei in the superior olivary complex (SOC) of mammals. It is classically thought to function as a relay station between the contralateral ventral cochlear nucleus and the lateral superior olive (LSO), playing a role among those brainstem nuclei that are involved in binaural hearing. In order to characterise the physiology and morphology at the cellular level of the major neuronal component of the MNTB, the principal cells, we have analysed these neurons in rats in vivo using intracellular recordings and horseradish peroxidase-labelling. Our data demonstrate that MNTB principal cells, when being stimulated acoustically via the contralateral ear, show a phasic-tonic response with an onset latency of 3.5 ms and a suppression of their spontaneous activity following stimulus offset. These neurons have an axonal morphology whose complexity has not yet been described. All cells (n=10) projected exclusively ipsilaterally and had terminal axonal arbors in a variety of auditory brainstem nuclei. At least two and maximally seven auditory targets were innervated by an individual cell. Each cell projected into the LSO and the superior paraolivary nucleus (SPN). Additional projections that were intrinsic to the SOC were often observed in the lateral nucleus of the Trapezoid Body and in periolivary regions, with only one cell projecting into the medial superior olive. Most, if not all, MNTB principal cells also had projections that were extrinsic to the SOC, as their axons ascended into the lateral lemniscus. In two neurons the ascending axon formed terminal arbors in the ventral nucleus of the lateral lemniscus, and the dorsal nucleus of the lateral lemniscus could be identified as a target of one neuron. The location of the cell bodies of the MNTB principal cells correlated with the neurons' best frequencies, thereby demonstrating a tonotopic organisation of the MNTB, with high frequencies being represented medially and low frequencies laterally. The axonal projections into the LSO and the SPN were also tonotopically organised and the alignment of the tonotopic axes was similar to that in the MNTB. Our results confirm previous data from other species and suggest that MNTB principal cells have a great amount of physiological and morphological similarities across mammalian species. Furthermore, the complexity of the axonal projections indicates that these neurons play a role in auditory information processing which goes far beyond their previously described classical role.
Achim Klug - One of the best experts on this subject based on the ideXlab platform.
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tonotopic alterations in inhibitory input to the medial nucleus of the Trapezoid Body in a mouse model of fragile x syndrome
The Journal of Comparative Neurology, 2017Co-Authors: Elizabeth A Mccullagh, Ernesto Salcedo, Molly M Huntsman, Achim KlugAbstract:Hyperexcitability and the imbalance of excitation/inhibition are one of the leading causes of abnormal sensory processing in Fragile X syndrome (FXS). The precise timing and distribution of excitation and inhibition is crucial for auditory processing at the level of the auditory brainstem, which is responsible for sound localization ability. Sound localization is one of the sensory abilities disrupted by loss of the Fragile X Mental Retardation 1 (Fmr1) gene. Using triple immunofluorescence staining we tested whether there were alterations in the number and size of presynaptic structures for the three primary neurotransmitters (glutamate, glycine and GABA) in the auditory brainstem of Fmr1 knockout mice. We found decreases in either glycinergic or GABAergic inhibition to the medial nucleus of the Trapezoid Body (MNTB) specific to the tonotopic location within the nucleus. MNTB is one of the primary inhibitory nuclei in the auditory brainstem and participates in the sound localization process with fast and well-timed inhibition. Thus, a decrease in inhibitory afferents to MNTB neurons should lead to greater inhibitory output to the projections from this nucleus. In contrast, we did not see any other significant alterations in balance of excitation/inhibition in any of the other auditory brainstem nuclei measured, suggesting that the alterations observed in the MNTB are both nucleus and frequency specific. We furthermore show that glycinergic inhibition may be an important contributor to imbalances in excitation and inhibition in FXS and that the auditory brainstem is a useful circuit for testing these imbalances. This article is protected by copyright. All rights reserved.
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recurrent inhibition to the medial nucleus of the Trapezoid Body in the mongolian gerbil meriones unguiculatus
PLOS ONE, 2016Co-Authors: Anna Dondzillo, John A Thompson, Achim KlugAbstract:Principal neurons in the medial nucleus of the Trapezoid Body (MNTB) receive strong and temporally precise excitatory input from globular bushy cells in the cochlear nucleus through the calyx of Held. The extremely large synaptic currents produced by the calyx have sometimes led to the view of the MNTB as a simple relay synapse which converts incoming excitation to outgoing inhibition. However, electrophysiological and anatomical studies have shown the additional presence of inhibitory glycinergic currents that are large enough to suppress action potentials in MNTB neurons at least in some cases. The source(s) of glycinergic inhibition to MNTB are not fully understood. One major extrinsic source of glycinergic inhibitory input to MNTB is the ventral nucleus of the Trapezoid Body. However, it has been suggested that MNTB neurons receive additional inhibitory inputs via intrinsic connections (collaterals of glycinergic projections of MNTB neurons). While several authors have postulated their presence, these collaterals have never been examined in detail. Here we test the hypothesis that collaterals of MNTB principal cells provide glycinergic inhibition to the MNTB. We injected dye into single principal neurons in the MNTB, traced their projections, and immunohistochemically identified their synapses. We found that collaterals terminate within the MNTB and provide an additional source of inhibition to other principal cells, creating an inhibitory microcircuit within the MNTB. Only about a quarter to a third of MNTB neurons receive such collateral inputs. This microcircuit could produce side band inhibition and enhance frequency tuning of MNTB neurons, consistent with physiological observations.
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glycinergic inhibition to the medial nucleus of the Trapezoid Body shows prominent facilitation and can sustain high levels of ongoing activity
Journal of Neurophysiology, 2014Co-Authors: Florian Mayer, Otto Albrecht, Anna Dondzillo, Achim KlugAbstract:Neurons in the medial nucleus of the Trapezoid Body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibit...
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Glycinergic inhibition to the medial nucleus of the Trapezoid Body shows prominent facilitation and can sustain high levels of ongoing activity.
Journal of Neurophysiology, 2014Co-Authors: Florian Mayer, Otto Albrecht, Anna Dondzillo, Achim KlugAbstract:Neurons in the medial nucleus of the Trapezoid Body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil (Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can susta...
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inhibitory projections from the ventral nucleus of the Trapezoid Body to the medial nucleus of the Trapezoid Body in the mouse
Frontiers in Neural Circuits, 2014Co-Authors: Otto Albrecht, Anna Dondzillo, Florian Mayer, John A Thompson, Achim KlugAbstract:Neurons in the medial nucleus of the Trapezoid Body (MNTB) receive prominent excitatory input through the calyx of Held, a giant synapse that produces large and fast excitatory currents. MNTB neurons also receive inhibitory glycinergic inputs that are also large and fast, and match the calyceal excitation in terms of synaptic strength. GABAergic inputs provide additional inhibition to MNTB neurons. Inhibitory inputs to MNTB modify spiking of MNTB neurons both in-vitro and in-vivo, underscoring their importance. Surprisingly, the origin of the inhibitory inputs to MNTB has not been shown conclusively. We performed retrograde tracing, anterograde tracing, immunohistochemical experiments, and electrophysiological recordings to address this question. The results support the ventral nucleus of the Trapezoid Body (VNTB) as at least one major source of glycinergic input to MNTB. VNTB fibers enter the ipsilateral MNTB, travel along MNTB principal neurons and produce several bouton-like presynaptic terminals. Further, the GABAergic component of the inhibitory input undergoes a developmental decrease in amplitude that is matched in time by a reduction in expression of a GABA synthetic enzyme in VNTB principal neurons.
John M Zook - One of the best experts on this subject based on the ideXlab platform.
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projections to the medial superior olive from the medial and lateral nuclei of the Trapezoid Body in rodents and bats
The Journal of Comparative Neurology, 1992Co-Authors: N Kuwabara, John M ZookAbstract:In this study we present direct evidence of axonal projections from both the medial and lateral nuclei of the Trapezoid Body to the medial superior olive. Projections were traced by intracellularly labeling cells and axons in a tissue slice preparation of two rodent species, Mus musculus and Meriones unguiculatus and two bat species, Eptesicus fuscus and Pteronotus parnellii. The main axon of most principal cells in the medial nucleus of the Trapezoid Body gives off one or more collateral branches which arborize within the medial superior olive. These collateral axons form small bouton-like swellings which primarily contact somata within the central cell column in the medial superior olive. Likewise, labeled elongate and multipolar cells of the lateral nucleus of the Trapezoid Body send axons to both the medial and lateral superior olives. These axons also form perisomatic contacts in both target nuclei. These two sets of projections may relay ascending input to the medial superior olive and the lateral superior olive; the medial nucleus of the Trapezoid Body is known to relay input from the contralateral ventral cochlear nucleus, and the lateral nucleus of the Trapezoid Body may relay input from the ipsilateral ventral cochlear nucleus. These projections offer two routes for indirect, possibly inhibitory input to reach the medial superior olive from both cochlear nuclei. These indirect, inhibitory pathways may parallel the direct excitatory projections the medial superior olive receives from each cochlear nucleus.
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afferents to the medial nucleus of the Trapezoid Body and their collateral projections
The Journal of Comparative Neurology, 1991Co-Authors: N Kuwabara, R A Dicaprio, John M ZookAbstract:Cells and axons that supply direct afferent input to the medial nucleus of the Trapezoid Body are described. Afferents were intracellularly labeled in brainstem tissue slices of two rodent and two bat species. The main afferents are calyciferous axons from globular bushy cells of the ventral cochlear nucleus. Calyciferous axons were highly consistent across species, projecting directly from the cochlear nucleus, across the midline in the Trapezoid Body, to the contralateral medial nucleus of the Trapezoid Body. Within the target nucleus, a typical axon turned sharply away from horizontal to form a large ending, the calyx of Held, around the soma of a single principal cell. Three groups of calyciferous axons were classified based on the path taken from bend to calyx. In subjects younger than four weeks, single axons often formed two calyces, each on a different cell. These calyx pairs were often found on adjacent or vertically aligned cells. In older animals, calyx pairs were more closely aligned, but fewer double calyx axons were seen. A secondary focus of this study was the system of thin collateral branches that characterizes calyciferous axons in all species. The projection patterns of these collaterals suggest that calyciferous axons may provide ascending input to periolivary cell groups with descending projections. In addition to calyciferous afferents, labeled cells that provide input to the medial nucleus of the Trapezoid Body from adjacent periolivary cell groups are described. Also described is a type of afferent that descends from the level of the lateral lemniscus to the medial nucleus of the Trapezoid Body.
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classification of the principal cells of the medial nucleus of the Trapezoid Body
The Journal of Comparative Neurology, 1991Co-Authors: N Kuwabara, John M ZookAbstract:Cells in the medial nucleus of the Trapezoid Body were intracellularly labeled in brainstem tissue slices of two bat and two rodent species. The main cell type found in this nucleus, the principal cell, is an important link in the relay of ascending projections from the contralateral cochlear nucleus to the lateral superior olive, completing an essential pathway for sound localization. Principal cells are often viewed as a highly homogeneous group with a consistent morphology as well as a common function. Intracellular labeling has revealed a number of new axonal and dendritic features of principal cells. Some of these features vary widely from cell to cell, suggesting that the population of principal cells contains several morphologically distinct subgroups. Similar subsets of principal cells were recognized in all species examined. Five subgroups were distinguished on the basis of the position of dendritic fields. Although the dendrites of most labeled cells were confined to the medial nucleus of the Trapezoid Body, some principal cells had dendrites that spread outside the nucleus to one of several adjacent periolivary cell groups. Cells were also found that had dendrites that spread medially across the midline and into the contralateral medial nucleus of the Trapezoid Body. Axonal projections were used to distinguish two additional subgroups of principal cells. All principal cells project to the lateral superior olive and virtually all have one or more secondary projections. There are two subgroups with unusual collateral projections: one with collaterals that extended to the lateral lemniscus and one with recurrent collateral axons.
