Development of a Robust Central Auditory Synapse in Congenital Deafness

2005 ◽  
Vol 94 (5) ◽  
pp. 3168-3180 ◽  
Author(s):  
M. Youssoufian ◽  
S. Oleskevich ◽  
B. Walmsley
Keyword(s):  
Brain Stem ◽  
Synaptic Strength ◽  
Congenital Deafness ◽  
Calyx Of Held ◽  
Developmentally Regulated ◽  
Release Probability ◽  
Receptor Complexes ◽  
Readily Releasable Pool ◽  
Medial Nucleus ◽  
Auditory Brain Stem

Within the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, there is a large central synapse known as the calyx of Held, which mediates high-fidelity glutamatergic transmission. We investigated the effects of congenital deafness on the development of pre- and postsynaptic parameters of synaptic strength at the calyx of Held. Whole cell recordings of evoked excitatory postsynaptic currents (EPSCs) and immunohistochemistry of GluR1–4 subunits were performed using brain stem slices from congenitally deaf or hearing mice at postnatal days P5 and P12. In both hearing and deaf mice there was a similar developmental decrease in the NMDA component of the evoked EPSC. There was a concurrent increase in release probability and number of release sites, contributing to a fivefold increase in evoked AMPA-mediated EPSC amplitude. The increase in release probability is opposite to that found in previous studies at the calyx of Held in the rat. There was also a seven- to eightfold increase in the size of the readily releasable pool of vesicles and a decrease in tetanic depression. The postsynaptic glutamate receptor subunits were similarly developmentally regulated and unaffected by deafness. GluR1 and 4 dominated at both ages. There was a decrease in expression of GluR1–3 from P5 to P12 and a shift from GluR2 to GluR3, indicating that AMPA receptor complexes at P12 are predominantly calcium-permeable. These results demonstrate that early development at this robust synapse proceeds normally with congenital deafness, suggesting that auditory nerve activity does not affect the development of synaptic strength at the calyx of Held.

Temporal Bone Findings in Keratitis, Ichthyosis, and Deafness Syndrome

1992 ◽  
Vol 101 (5) ◽  
pp. 413-416 ◽  
Author(s):  
Toshihiro Tsuzuku ◽  
Kimitaka Kaga ◽  
Akihiko Shibata ◽  
Shuichi Kanematsu ◽  
Schyu Ohde
Keyword(s):  
Brain Stem ◽  
Inner Ear ◽  
Temporal Bone ◽  
Congenital Deafness ◽  
Auditory Brain Stem Response ◽  
Congenital Ichthyosis ◽  
Auditory Brain Stem ◽  
Pathologic Findings ◽  
Brain Stem Response

In 1981, the term KID syndrome was suggested for patients with congenital ichthyosis associated with deafness and keratitis. We had a chance to examine the temporal bone of an infant with this syndrome. This patient showed no auditory brain stem response in either ear. Temporal bone studies revealed cochleosaccular abnormality. These findings are offered as a possible explanation for the patient's deafness. The pathologic inner ear findings of congenital deafness syndromes associated with ichthyosis have been heretofore reported in Refsum's syndrome and in a case with universal alopecia. In these cases, the temporal bone pathologic findings were a result of cochleosaccular abnormality. From our case and previous reports, it is suggested that the deafness associated with congenital ichthyosis might be the result of cochleosaccular abnormality.

scholarly journals Target-specific regulation of presynaptic release properties at auditory nerve terminals in the avian cochlear nucleus

2016 ◽  
Vol 115 (3) ◽  
pp. 1679-1690 ◽  
Author(s):  
J. Ahn ◽  
K. M. MacLeod
Keyword(s):  
Brain Stem ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Auditory Information ◽  
Nerve Terminals ◽  
Release Probability ◽  
Auditory Brain Stem ◽  
Presynaptic Release ◽  
Specific Regulation ◽  
Synaptic Dynamics

Short-term synaptic plasticity (STP) acts as a time- and firing rate-dependent filter that mediates the transmission of information across synapses. In the auditory brain stem, the divergent pathways that encode acoustic timing and intensity information express differential STP. To investigate what factors determine the plasticity expressed at different terminals, we tested whether presynaptic release probability differed in the auditory nerve projections to the two divisions of the avian cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Estimates of release probability were made with an open-channel blocker of N-methyl-d-aspartate (NMDA) receptors. Activity-dependent blockade of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) with application of 20 μM (+)-MK801 maleate was more rapid in NM than in NA, indicating that release probability was significantly higher at terminals in NM. Paired-pulse ratio (PPR) was tightly correlated with the blockade rate at terminals in NA, suggesting that PPR was a reasonable proxy for relative release probability at these synapses. To test whether release probability was similar across convergent inputs onto NA neurons, PPRs of different nerve inputs onto the same postsynaptic NA target neuron were measured. The PPRs, as well as the plasticity during short trains, were tightly correlated across multiple inputs, further suggesting that release probability is coordinated at auditory nerve terminals in a target-specific manner. This highly specific regulation of STP in the auditory brain stem provides evidence that the synaptic dynamics are tuned to differentially transmit the auditory information in nerve activity into parallel ascending pathways.

The Pool of Fast Releasing Vesicles Is Augmented by Myosin Light Chain Kinase Inhibition at the Calyx of Held Synapse

2008 ◽  
Vol 99 (4) ◽  
pp. 1810-1824 ◽  
Author(s):  
Geetha Srinivasan ◽  
Jun Hee Kim ◽  
Henrique von Gersdorff
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Regulatory Protein ◽  
Developmental Studies ◽  
Calyx Of Held ◽  
Release Probability ◽  
Readily Releasable Pool ◽  
Action Potential Waveform ◽  
Vesicle Pool

Synaptic strength is determined by release probability and the size of the readily releasable pool of docked vesicles. Here we describe the effects of blocking myosin light chain kinase (MLCK), a cytoskeletal regulatory protein thought to be involved in myosin-mediated vesicle transport, on synaptic transmission at the mouse calyx of Held synapse. Application of three different MLCK inhibitors increased the amplitude of the early excitatory postsynaptic currents (EPSCs) in a stimulus train, without affecting the late steady-state EPSCs. A presynaptic locus of action for MLCK inhibitors was confirmed by an increase in the frequency of miniature EPSCs that left their average amplitude unchanged. MLCK inhibition did not affect presynaptic Ca2+ currents or action potential waveform. Moreover, Ca2+ imaging experiments showed that [Ca2+]i transients elicited by 100-Hz stimulus trains were not altered by MLCK inhibition. Studies using high-frequency stimulus trains indicated that MLCK inhibitors increase vesicle pool size, but do not significantly alter release probability. Accordingly, when AMPA-receptor desensitization was minimized, EPSC paired-pulse ratios were unaltered by MLCK inhibition, suggesting that release probability remains unaltered. MLCK inhibition potentiated EPSCs even when presynaptic Ca2+ buffering was greatly enhanced by treating slices with EGTA-AM. In addition, MLCK inhibition did not affect the rate of recovery from short-term depression. Finally, developmental studies revealed that EPSC potentiation by MLCK inhibition starts at postnatal day 5 (P5) and remains strong during synaptic maturation up to P18. Overall, our data suggest that MLCK plays a crucial role in determining the size of the pool of synaptic vesicles that undergo fast release at a CNS synapse.

scholarly journals Activity-dependent formation and location of voltage-gated sodium channel clusters at a CNS nerve terminal during postnatal development

2017 ◽  
Vol 117 (2) ◽  
pp. 582-593 ◽  
Author(s):  
Jie Xu ◽  
Emmanuelle Berret ◽  
Jun Hee Kim
Keyword(s):  
Brain Stem ◽  
Nerve Terminal ◽  
Low Frequency ◽  
Presynaptic Terminal ◽  
Scaffolding Protein ◽  
Unmyelinated Axon ◽  
Voltage Gated ◽  
Medial Nucleus ◽  
Auditory Brain Stem ◽  
Activity Dependent

In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Nav) channels clustered at nodes of Ranvier. Changes in Nav channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. We studied the activity-dependent formation of Nav channel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Nav channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Nav channel cluster at the nodes was present before hearing onset. Initiation of heminodal Nav channel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Nav channels did not form clusters and maintained broad expression, but Nav channel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Nav channel to the calyx across the mediolateral axis of the medial nucleus of the trapezoid body (MNTB) developed after hearing onset. In the medial MNTB, where neurons respond best to high-frequency sounds, the heminodal Nav channel cluster was located closer to the terminal than in the lateral MNTB, where neurons respond best to low-frequency sounds. Thus sound-mediated neuronal activities are potentially associated with the refinement of the heminode adjacent to the presynaptic terminal in the auditory brain stem. NEW & NOTEWORTHY Clustering of voltage-gated sodium (Nav) channels and their distribution along the axon, specifically at the unmyelinated axon segment next to the nerve terminal, are essential for tuning propagated action potentials. Nav channel clusters near the nerve terminal and their location as a function of neuronal position along the mediolateral axis are controlled by auditory inputs after hearing onset. Thus sound-mediated neuronal activity influences the tonotopic organization of Nav channels at the nerve terminal in the auditory brain stem.

scholarly journals Structure-function relation of the developing calyx of Held synapse in vivo

2020 ◽  
Author(s):  
Martijn C. Sierksma ◽  
Johan A. Slotman ◽  
Adriaan B. Houtsmuller ◽  
J. Gerard G. Borst
Keyword(s):  
Structure Function ◽  
Glutamate Transporters ◽  
Synaptic Strength ◽  
Target Cells ◽  
List Type ◽  
Calyx Of Held ◽  
Synaptic Terminals ◽  
Medial Nucleus ◽  
Vesicular Glutamate Transporters

AbstractIn adult rodents, a principal neuron in the medial nucleus of the trapezoid (MNTB) is generally contacted by a single, giant axosomatic terminal called the calyx of Held. How this one-on-one relation is established is still unknown, but anatomical evidence suggests that during development principal neurons are innervated by multiple calyces, which may indicate calyceal competition. However, in vivo electrophysiological recordings from principal neurons indicated that only a single strong synaptic connection forms per cell. To test whether a mismatch exists between synaptic strength and terminal size, we compared the strength of synaptic inputs with the morphology of the synaptic terminals. In vivo whole-cell recordings of the MNTB neurons from newborn Wistar rats of either sex were made while stimulating their afferent axons, allowing us to identify multiple inputs. The strength of the strongest input increased to calyceal levels in a few days across cells, while the strength of the second strongest input was stable. The recorded cells were subsequently immunolabeled for vesicular glutamate transporters (VGluT) to reveal axosomatic terminals with structured-illumination microscopy. Synaptic strength of the strongest input was correlated with the contact area of the largest VGluT cluster at the soma (r = 0.8), and no indication of a mismatch between structure and strength was observed. Together, our data agree with a developmental scheme in which one input strengthens and becomes the calyx of Held, but not with multi-calyceal competition.Key points summaryDuring development the giant, auditory calyx of Held forms a one-to-one connection with a principal neuron of the medial nucleus of the trapezoid body.While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi-calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure-function discrepancy.We correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labeling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT).During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma.As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure-function discrepancy.

Multiple Large Inputs to Principal Cells in the Mouse Medial Nucleus of the Trapezoid Body

2004 ◽  
Vol 92 (1) ◽  
pp. 545-552 ◽  
Author(s):  
Jeremy B. Bergsman ◽  
Pietro De Camilli ◽  
David A. McCormick
Keyword(s):  
Sound Localization ◽  
Excitatory Input ◽  
Nerve Terminals ◽  
Calyx Of Held ◽  
Anatomical Studies ◽  
Principal Cells ◽  
Medial Nucleus ◽  
Central Synapse ◽  
Auditory Brain Stem ◽  
Trapezoid Body

The calyx of Held is a giant nerve terminal that forms a synapse directly onto the principal cells of the medial nucleus of the trapezoid body (MNTB) in the mammalian auditory brain stem. This central synapse, which is involved in sound localization, has become widely used for studying synaptic transmission. Anatomical studies of this nucleus have indicated that each principal cell is innervated by only one calyx. Here we use previously established electrophysiological criteria of excitatory postsynaptic current amplitude, kinetics, and transmitter type, as well as other characteristics commonly reported for this synapse, to examine the input properties of principal neurons. Our findings indicate that some principal cells receive more than one strong excitatory input. These inputs meet previously established electrophysiological criteria for identification as calyceal nerve terminals. Implications for the execution and analysis of experiments to avoid errors due to such multiple inputs are discussed.

Anatomy and Physiology of Principal Cells of the Medial Nucleus of the Trapezoid Body (MNTB) of the Cat

1998 ◽  
Vol 79 (6) ◽  
pp. 3127-3142 ◽  
Author(s):  
Philip H. Smith ◽  
Philip X. Joris ◽  
Tom C. T. Yin
Keyword(s):  
Brain Stem ◽  
Cell Body ◽  
Superior Olive ◽  
Principal Cells ◽  
Anatomy And Physiology ◽  
Medial Nucleus ◽  
Bushy Cell ◽  
Auditory Brain Stem ◽  
Trapezoid Body ◽  
Bushy Cells

Smith, Philip H., Philip X. Joris, and Tom C. T. Yin. Anatomy and physiology of principal cells of the medial nucleus of the trapezoid body (MNTB) of the cat. J. Neurophysiol. 79: 3127–3142, 1998. We have recorded from principal cells of the medial nucleus of the trapezoid body (MNTB) in the cat's superior olivary complex using either glass micropipettes filled with Neurobiotin or horseradish peroxidase for intracellular recording and subsequent labeling or extracellular metal microelectrodes relying on prepotentials and electrode location. Labeled principal cells had cell bodies that usually gave rise to one or two primary dendrites, which branched profusely in the vicinity of the cell. At the electron microscopic (EM) level, there was a dense synaptic terminal distribution on the cell body and proximal dendrites. Up to half the measured cell surface could be covered with excitatory terminals, whereas inhibitory terminals consistently covered about one-fifth. The distal dendrites were very sparsely innervated. The thick myelinated axon originated from the cell body and innervated nuclei exclusively in the ipsilateral auditory brain stem. These include the lateral superior olive (LSO), ventral nucleus of the lateral lemniscus, medial superior olive, dorsomedial and ventromedial periolivary nuclei, and the MNTB itself. At the EM level the myelinated collaterals gave rise to terminals that contained nonround vesicles and, in the LSO, were seen terminating on cell bodies and primary dendrites. Responses of MNTB cells were similar to their primary excitatory input, the globular bushy cell (GBC), in a number of ways. The spontaneous spike rate of MNTB cells with low characteristic frequencies (CFs) was low, whereas it tended to be higher for higher CF units. In response to short tones, a low frequency MNTB cell showed enhanced phase-locking abilities, relative to auditory nerve fibers. For cells with CFs >1 kHz, the short tone response often resembled the primary-like with notch response seen in many globular bushy cells, with a well-timed onset component. Exceptions to and variations of this standard response were also noted. When compared with GBCs with comparable CFs, the latency of the MNTB cell response was delayed slightly, as would be expected given the synapse interposed between the two cell types. Our data thus confirm that, in the cat, the MNTB receives and converts synaptic inputs from globular bushy cells into a reasonably accurate reproduction of the bushy cell spike response. This MNTB cell output then becomes an important inhibitory input to a number of ipsilateral auditory brain stem nuclei.

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