scholarly journals Strengthening of the efferent olivocochlear system leads to synaptic dysfunction and tonotopy disruption of a central auditory nucleus

2018 ◽  
Author(s):  
Mariano N. Di Guilmi ◽  
Luis E. Boero ◽  
Valeria C. Castagna ◽  
Adrián Rodríguez-Contreras ◽  
Carolina Wedemeyer ◽  
...  

AbstractThe auditory system in many mammals is immature at birth but precisely organized in adults. Spontaneous activity in the inner ear plays a critical role in guiding this process. This is shaped by an efferent pathway that descends from the brainstem and makes transient direct synaptic contacts with inner hair cells (IHCs). In this work, we used an α9 cholinergic receptor knock-in mouse model (of either sex) with enhanced medial efferent activity (Chrna9L9’T, L9’T) to understand the role of the olivocochlear system in the correct establishment of auditory circuits. Wave III of auditory brainstem responses (which represents synchronized activity of synapses within the superior olivary complex) were smaller in L9’T mice, suggesting a central dysfunction. The mechanism underlying this functional alteration was analysed in brain slices containing the medial nucleus of the trapezoid body (MNTB), where neurons are topographically organized along a medio-lateral axis. The topographic organization of MNTB physiological properties observed in WT mice was abolished in the L9’T mice. Additionally, electrophysiological recordings in slices evidenced MNTB synaptic alterations, which were further supported by morphological alterations. The present results suggest that the transient cochlear efferent innervation to IHCs during the critical period before the onset of hearing is involved in the refinement of topographic maps as well as in setting the correct synaptic transmission at central auditory nuclei.Significance StatementCochlear inner hair cells of altricial mammals display spontaneous electrical activity before hearing onset. The pattern and firing rate of these cells is crucial for the correct maturation of the central auditory pathway. A descending efferent innervation from the central nervous system contacts hair cells during this developmental window. The function of this transient efferent innervation remains an open question. The present work shows that the genetic enhancement of efferent function disrupts the orderly topographic distribution at the medial nucleus of the trapezoid body level and causes severe synaptic dysfunction. Thus, the transient efferent innervation to the cochlea is necessary for the correct establishment of the central auditory circuitry.

2005 ◽  
Vol 94 (6) ◽  
pp. 3826-3835 ◽  
Author(s):  
Joshua S. Green ◽  
Dan H. Sanes

Despite the peripheral and central immaturities that limit auditory processing in juvenile animals, they are able to lateralize sounds using binaural cues. This study explores a central mechanism that may compensate for these limitations during development. Interaural time and level difference processing by neurons in the superior olivary complex depends on synaptic inhibition from the medial nucleus of the trapezoid body (MNTB), a group of inhibitory neurons that is activated by contralateral sound stimuli. In this study, we examined the maturation of coding properties of MNTB neurons and found that they receive an inhibitory influence from the ipsilateral ear that is modified during the course of postnatal development. Single neuron recordings were obtained from the MNTB in juvenile (postnatal day 15–19) and adult gerbils. Approximately 50% of all recorded MNTB neurons were inhibited by ipsilateral sound stimuli, but juvenile neurons displayed a much greater suppression of firing as compared with those in adults. A comparison of the prepotential and postsynaptic action potential indicated that inhibition occurred at the presynaptic level, likely within the cochlear nucleus. A simple linear model of level difference detection by lateral superior olivary neurons that receive input from MNTB suggested that inhibition of the MNTB may expand the response of LSO neurons to physiologically realistic level differences, particularly in juvenile animals, at a time when these cues are reduced.


2021 ◽  
Author(s):  
Alena Maul ◽  
Saša Jovanovic ◽  
Antje-Kathrin Huebner ◽  
Nicola Strenzke ◽  
Tobias Moser ◽  
...  

Before hearing onset (postnatal day 12 in mice), inner hair cells (IHC) spontaneously fire action potentials thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISC) of Kölliker's organ through the activity of the Ca2+ activated Cl- channel TMEM16A. Here we show that conditional deletion of Tmem16a in mice disrupts the generation of Ca2+ waves within Köllike's organ, reduces the burst firing activity and the frequency-selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the refinement of MNTB projections to the lateral superior olive (LSO). These results reveal the importance of the activity of Köllike's organ for the refinement of central auditory connectivity. In addition, our study suggests a mechanism for the generation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.


1994 ◽  
Vol 110 (1) ◽  
pp. 84-92 ◽  
Author(s):  
Chiyeko Tsuchitani

Single-unit responses of cat superior olivary complex neurons to acoustic stimuli were examined to determine whether the units' action potentials were sufficiently synchronized to contribute to the brain stem evoked response. The medial nucleus of the trapezoid body and lateral superior olive are two major nuclei within the cat superior olivary complex. The first-spike discharge latencies of medial nucleus of the trapezoid body and lateral superior olivary neurons to monaural presentations of tone burst stimuli were measured as a function of stimulus level. Evidence is provided to support the hypotheses that in cat the medial nucleus of the trapezoid body may contribute directly to the monaural brain stem evoked response by producing action potentials synchronized to stimulus onset and may also contribute indirectly to the brain stem evoked response binaural difference wave bc by inhibiting the lateral superior olive unit excitatory responses synchronized to stimulus onset.


2021 ◽  
Vol 15 ◽  
Author(s):  
Nichole L. Beebe ◽  
Chao Zhang ◽  
R. Michael Burger ◽  
Brett R. Schofield

The superior olivary complex (SOC) is a major computation center in the brainstem auditory system. Despite previous reports of high expression levels of cholinergic receptors in the SOC, few studies have addressed the functional role of acetylcholine in the region. The source of the cholinergic innervation is unknown for all but one of the nuclei of the SOC, limiting our understanding of cholinergic modulation. The medial nucleus of the trapezoid body, a key inhibitory link in monaural and binaural circuits, receives cholinergic input from other SOC nuclei and also from the pontomesencephalic tegmentum. Here, we investigate whether these same regions are sources of cholinergic input to other SOC nuclei. We also investigate whether individual cholinergic cells can send collateral projections bilaterally (i.e., into both SOCs), as has been shown at other levels of the subcortical auditory system. We injected retrograde tract tracers into the SOC in gerbils, then identified retrogradely-labeled cells that were also immunolabeled for choline acetyltransferase, a marker for cholinergic cells. We found that both the SOC and the pontomesencephalic tegmentum (PMT) send cholinergic projections into the SOC, and these projections appear to innervate all major SOC nuclei. We also observed a small cholinergic projection into the SOC from the lateral paragigantocellular nucleus of the reticular formation. These various sources likely serve different functions; e.g., the PMT has been associated with things such as arousal and sensory gating whereas the SOC may provide feedback more closely tuned to specific auditory stimuli. Further, individual cholinergic neurons in each of these regions can send branching projections into both SOCs. Such projections present an opportunity for cholinergic modulation to be coordinated across the auditory brainstem.


2006 ◽  
Vol 95 (3) ◽  
pp. 1499-1508 ◽  
Author(s):  
Alexander Kadner ◽  
Randy J. Kulesza ◽  
Albert S. Berrebi

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 superior paraolivary nucleus (SPON) of anesthetized rats were studied. MNTB neurons produced primary-like responses to pure tones and displayed a period of suppressed spontaneous activity after stimulus offset. In contrast, neurons of the SPON, which receive a strong glycinergic input from MNTB, showed very little or no spontaneous activity and responded with short bursts of action potentials after the stimulus offset. Because SPON spikes were restricted to the same time window during which suppressed spontaneous activity occurs in the MNTB, we presume that SPON offset activity represents a form of postinhibitory rebound. Using characteristic frequency tones of 2- to 1,000-ms duration presented 20 dB above threshold, we show that the profundity and duration of the suppression of spontaneous activity in MNTB as well as the magnitude and first spike latency of the SPON offset response depend on stimulus duration as well as on stimulus intensity, showing a tradeoff between intensity and duration. Pairwise comparisons of the responses to stimuli of various durations revealed that the duration sensitivity in both nuclei is sharpest for stimuli <50 ms.


1980 ◽  
Vol 89 (5_suppl) ◽  
pp. 114-120 ◽  
Author(s):  
W. Bruce Warr

The origins and terminations of the olivocochlear bundle, which provides an efferent innervation to the organ of Corti, are described on the basis of experiments using axonal transport of tracer substances and light microscopy in the cat. The cells of origin were labeled by the retrograde tracer horseradish peroxidase which was injected unilaterally into the cochlea. Labeled cells in the superior olivary complex could be dichotomized according to their location (lateral or medial), their size (small or large), and their preferred side of projection (uncrossed or crossed). All labeled olivocochlear neurons exhibited a positive reaction for acetylcholinesterase. To determine the cochlear projections of the neurons, injections of a radioactive amino acid were made into either the lateral or medial olivocochlear cell group. After allowing time for synthesis and axonal transport of radio-labeled protein to reach synaptic endings in the cochleas, the tissue sections of these specimens were processed for autoradiography. The results indicate that lateral olivocochlear neurons project to the region beneath the inner hair cells of both sides, whereas medial olivocochlear neurons project to the region beneath the outer hair cells of both sides. These findings are in substantial accord with previous experimental work but suggest that the organ of Corti receives a dual efferent innervation which is organized according to the location and morphology of its cells of origin. Accordingly, it is proposed that the two efferent components of the cochlear innervation described here be referred to as the lateral and medial olivocochlear systems, replacing the current designations of crossed and uncrossed olivocochlear bundles, the latter which are demonstrably heterogeneous in their origins and terminations and, probably, also in their functions.


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