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Differentiation of nerve endings in the cochlear nucleus on morphological and experimental basis.

The axo-somatic terminals which synapse with the large spherical cells in the antero-ventral cochlear nucleus of the guinea pig are subdivided into three groups by means of different stereological form of their synaptic vesicles. Unilateral stimulation as well as long-term degeneration of the cochlear nerve produce significant changes of the cross sectional area of the terminals and the number of their mitochondria, when compared to the contralateral control. Both parameters are increased after stimulation and decreased following degeneration. These changes occur in different extent in the three groups of terminals. The discussion of these findings has led to the following conclusions: (1) The volume of synaptic terminals and the number of the enclosed mitochondria display the most pronounced plastic changes. Therefore these parameters seem to be very indicative for the study of function-related changes. (2) The volume of terminals, the quantity of their mitochondria, and the total sum of membranes may be increased under stimulation by actual acceleration of the axoplasmatic flow rate and by incorporation of the preterminal portion of the axon. (3) The presence of at least three types of terminals is evident from the different form of their synaptic vesicles and in addition, from their different response to our experimental conditions. It is not decided from the present findings, whether the bouton-like terminals and bulbs of the afferent cochlear nerve axons contain the same type of synaptic vesicles or whether these axons produce heterotypic terminals.

Animals↗

Morphology of the primary posterior plexus of the rat cochlear nucleus.

Golgi impregnation results confirm the existence of a plexus (previously described with horseradish peroxidase tracing techniques) located in the posteroventral cochlear nucleus. The bulk of axons involved in this plexus could be traced to their origin in the root, and were not related to the V-bifurcating fibres, though some of the posterior branches of the latter contributed to the plexus. The internal structure of the plexus, and the different types of endings are described. These findings are discussed in relation to previous Golgi studies, especially those referring to the neuron and axon population of this area.

Afferent Pathways↗

Afferent regulation of oxidative stress in the chick cochlear nucleus.

The chick auditory brain stem has been a useful model system for examining the afferent-dependent signals that regulate postsynaptic neurons. Like other sensory systems, compromised afferent input results in rapid death and atrophy of postsynaptic neurons. The present paper explores the possible contributions of an oxidative stress pathway in determining neuronal fate following deafferentation. Levels of reactive oxygen species, lipid damage measured by 4-hydroxynonenal formation, and a compensatory reactive oxygen species-induced response regulated by glutathione s transferase M1 and the reactive oxygen species-sensitive transcriptional factor, nuclear respiratory factor 1 were examined. Unilateral cochlea removal surgery was performed on young posthatch chicks. Labeling in the cochlear nucleus, nucleus magnocellularis, on opposite sides of the same tissue sections were compared by densitometry. The results showed a dramatic increase in reactive oxygen species in the deafferented nucleus magnocellularis by 6 h following cochlea removal. This increase in reactive oxygen species was accompanied by lipid damage and a compensatory upregulation of both glutathione s transferase M1 and nuclear respiratory factor 1. Double-labeling revealed that glutathione s transferase M1 expression was highest in neurons that were likely to survive deafferentation, as assessed immunocytochemically with Y10b, a marker for ribosomal integrity. Together, these data suggest reactive oxygen species are generated and a compensatory detoxifying pathway is upregulated in the first few hours following deafferentation. This is consistent with the hypothesis that oxidative stress plays a role in determining whether a given neuron survives following deafferentation.

Afferent Pathways↗

A simplified application of systematic field sampling and low-cost video recording set-up for viewing disector pairs - exemplified in the rat cochlear nucleus.

A description of a simple and efficient way of systematic field sampling along with a low-cost set-up for simultaneous viewing of physical disector pairs at the light microscopic level is presented. So far the use of a programmable motorized stage for the former purpose and two projection microscopes for the latter have proved to be the most efficient and fastest solutions, but the relatively high expense of purchasing such equipment constitutes a major impediment to the widespread use of such stereological methods. We describe practical applications of two new cost-effective alternative approaches derived from existing ones. These approaches are used in estimating the total number of neurones in the cochlear nucleus of the rat and involve the systematic selection of section fields at a magnification significantly lower than the magnification used for counting and a video recording set-up for comparing section pairs. Apart from providing a cheap way for the implementation of the physical disector, the main feature of the application, which may also encourage its use, is that it provides an efficient and simple design for systematic area sampling without requiring any specialized equipment. The same is true for optical disector designs, where the procedure is simplified even further.

Animals↗

Neuronal types in the deep dorsal cochlear nucleus of the cat: I. Giant neurons.

Large or "giant" neurons (average somatic diameter greater than 22 micron) of the dorsal cochlear nucleus (DCN) have been carefully described in this light (LM) and electron (EM) microscopic study of normal Nissl-stained and Golgi-impregnated cat brain stems. These neurons can be roughly classed by somatic shape (width:length ratio = r) as elongate (r less than 0.65), ovoid (0.65 less than or equal to r less than 0.75), or spherical (0.75 less than or equal to r less than or equal to 1.0) in Nissl-stained sections. However, orientation and location of somata, size, number, and distribution of basal dendrites and other cytological features seen in Nissl material provided five, easily recognized classes of large neurons: elongate bipolar, elongate multipolar, globular, radiate, and oriented multipolar giant cells. Further cytological details of the dendritic tree and axonal morphology of these neurons, observed in rapid Golgi impregnations of cat and kitten brain stems, extended these descriptive categories of giant neurons. These same deep DCN giant cells were identified in thick plastic sections and in subsequent thin sections. Thin sections showed further neuronal distinctions by relative density of somatic and dendritic synaptic inputs. All giant cells have dense synaptic inputs to basal and primary dendrites but only elongate multipolar and radiate giant cell somata have nearly continuous synaptic coverage of somata. Many axodendritic terminals and some axosomatic endings resemble cochlear endings as identified on fusiform cells of the DCN. Nauta preparations after ipsilateral cochlear ablations have confirmed (1) cochlear input to all giant cell types and (2) different patterns of input to each type. Hence, each giant cell type must process incoming auditory signals, but each cell must receive slightly different primary information. Since some giant cells of each type had observable axons heading into the dorsal acoustic stria, they must all carry encoded primary information to higher auditory centers.

Animals↗

Latency of unit responses in cochlear nucleus determined in two different ways.

The latency revealed by poststimulus time histograms of the responses of single units in the cochlear nucleus to tone bursts was compared with the latency of the change in discharge frequency in response to small increments in the amplitude of the stimulus. The latter was derived on the basis of statistical signal analysis of the discharge pattern in response to tones amplitude modulated with pseudorandom noise. The "step response" of the system was computed by time integration of the cross covariance between modulation and spike density. The following observations can be made: 1. The latency of the responses to tone bursts always decreased with increasing sound intensity, whereas the latency of the step response was almost constant for intensities from immediately above threshold to the highest intensity used (60-70 dB above threshold). 2. In most units the latency revealed by the PST histogram of the responses to tone bursts approached the value of latency of the step response asymptotically. 3. In some units with longer latency, the latency of the response to tone bursts was many times greater than the latency of the step response, even at high sound intensities. 4. A histogram of latency values of the step response of the units studied showed narrow peaks at 2.8 and 4.7 ms. 5. On the basis of the present results it is concluded that the latency values of the step response represent the true sum of synaptic and axon dendritical propagation delay, whereas the latency of the responses to tone bursts also includes the temporal summation at the synaptic level.

Animals↗

Single unit activity in the guinea-pig cochlear nucleus during sleep and wakefulness.

The effects of waking and sleep on the response properties of auditory units in the ventral cochlear nucleus (CN) were explored by using extracellular recordings in chronic guinea-pigs. Significant increases and decreases in firing rate were detected in two neuronal groups, a) the "sound-responding" and b) the "spontaneous" (units that do not show responses to any acoustic stimuli controlled by the experimenter). The "spontaneous" may be considered as belonging to the auditory system because the corresponding units showed a suppression of their discharge when the receptor was destroyed. The auditory CN units were characterized by their PSTH in response to tones at their characteristic frequency and also by the changes in firing rate and probability of discharge evaluated during periods of waking, slow wave and paradoxical sleep. The CNS performs functions dependent on sensory inputs during wakefulness and sleep phases. By studying the auditory input at the level of the ventral CN with constant sound stimuli, it was shown that, in addition to the firing rate shifts, some units presented changes in the temporal probability of discharge, implying central actions on the corresponding neurons. The mean latency of the responses, however, did not show significant changes throughout the sleep-waking cycle. The auditory efferent pathways are postulated to modulate the auditory input at CN level during different animal states. The probability of firing and the changes in the temporal pattern, as shown by the PSTH, are thus dependent on both the auditory input and the functional brain state related to the sleep-waking cycle.

Acoustic Stimulation↗

Evaluation of streamlined programming procedures for the Nucleus cochlear implant with the Contour electrode array.

OBJECTIVE: The objective of this study was to evaluate streamlined programming procedures for the Nucleus cochlear implant system with the Contour electrode array. DESIGN: Phase 1 involved an examination of the clinical MAPs for the first 103 recipients implanted with the Contour electrode array in the Melbourne Cochlear Implant Clinic, to examine the ability to predict the entire MAP based on a smaller number of clinically determined T- and/or C-levels. In phase 2, a subset of the streamlined procedures was selected and clinically evaluated, using speech perception and subjective preference measures. In the first study, the clinical MAP was compared with a MAP based on interpolating across three behavioral T-levels and three behavioral C-levels in a group of newly implanted subjects. The second study investigated the use of a single interpolated profile as the basis to creating the entire MAP. Initial evaluation compared the clinical MAP with two streamlined MAPs, one in which the C-level profile was derived from interpolation across a subset of T-levels and one in which the T-level profile was derived from interpolation across a subset of C-levels. In this case, the interpolated profile was based on five behavioral measures. Subsequently, the use of either three or a single T-level measure as the basis for the interpolated T-level profile was evaluated. Eighteen subjects, who were experienced with the clinical MAP before enrollment in the study, participated in the initial evaluation. The subjects were selected to include a group whose RMS deviation from clinical MAP levels, as determined in Phase 1, was greater than that of the wider population. RESULTS: The Phase 1 analysis showed that as expected, larger differences were observed between the clinical and derived MAP levels as interpolation was applied across fewer measured electrodes and that the use of a single interpolated profile to create the entire MAP resulted in the greatest deviation. No significant group mean difference was found in speech perception scores for newly implanted subjects when mapped with the clinical versus the streamlined MAP based on three behavioral T- and three behavioral C-level measures. For some individual subjects, scores were higher with the streamlined MAP. Subjective reports from the comparative performance questionnaire were consistent with these findings. No significant group mean difference in speech perception scores was found in comparing the clinical MAP with the streamlined MAPs based on a single interpolated T- or C-level profile created from five behavioral measures. Individual effects were observed; however, there was no consistent finding across subjects. The use of three rather than five behavioral T-level measures in the procedure did not result in significantly lower group mean scores; however, significantly poorer scores were obtained for three of the 10 individual subjects. The use of a MAP based on a single behavioral measure did result in poorer speech perception scores when compared with the MAP based on five behavioral T-level measures. These findings were consistent with subjective results from the performance questionnaires administered to determine preference for program across a range of listening situations. CONCLUSIONS: Two streamlined programming procedures are recommended for use in the clinical setting: (1) interpolating across three measured T-levels and three measured C-levels and (2) interpolating across five measured T- or C-levels and using the interpolated profile for fitting of the alternative profile.

Adult↗

Coding of voice source information in the Nucleus cochlear implant system.

Two studies are reported in which the effectiveness of explicitly coding voicing and fundamental frequency information for the Nucleus cochlear implant was investigated. In the first study, the voicing perception of a group of three experienced Multipeak users was evaluated when they were using Multipeak and a modified Multipeak in which the explicit fundamental frequency and voicing cues were eliminated and replaced with a 250-Hz constant rate of stimulation. The results of consonant and monosyllabic word tests showed that there was no significant difference in the subjects' ability to discriminate voicing. In the second study, the ability of a group of five experienced users of the constant rate spectral maxima sound processor (SMSP) strategy to discriminate suprasegmental contrasts was evaluated when they were using the SMSP strategy and a modified SMSP strategy that included a rate-encoded representation of the fundamental frequency on the most apical stimulation channel. The results of intonation, roving stress, and question-statement tests showed that there was no significant difference between the scores recorded with these strategies. Since the temporal voicing cue is not a primary cue to voicing discrimination for Multipeak users, and the provision of an additional rate cue to the SMSP strategy does not improve SMSP users' ability to discriminate suprasegmental contrasts, the results of these studies indicate that in the cases investigated, the coding of voice source information by rate of stimulation does not significantly augment the cues present in the spatially distributed constant rate stimulation pattern.

Adult↗

Differential afferent projections to the inferior colliculus from the cochlear nucleus in the albino mouse.

The axonal projections from the cochlear nuclear complex to the inferior colliculus (IC) were examined using the retrograde transport of horseradish peroxidase. Thin sheets of neurons in the dorsal and ventral cochlear nuclei were found to project axons in a topographic fashion to restricted laminae of the central nucleus of the IC; the dorsal cochlear nucleus was also found to project axons to the external cortex. No projections were detected from the cochlear nuclear complex to the dorsal cortex of the IC.

Afferent Pathways↗

Postnatal development of auditory nerve and cochlear nucleus neuronal responses in kittens.

Neurons located within the auditory periphery of kittens (i.e., primary auditory nerve fibers and neurons of the cochlear nucleus (CN) exhibit similar response properties throughout the early stages of postnatal development. Neural thresholds to acoustic stimuli are uniformly high, spontaneous and acoustically-evoked discharge rates are low, input/output slopes are shallow, and temporal discharge patterns are markedly immature. Phase-locking abilities are poor in developing mammals and all neurons exhibit broad bandpass tuning curves, with center frequencies clustering near 1.5 kHz. Throughout the first week, response thresholds, maximum discharge rates, rate-intensity slopes, dynamic ranges and other response indices remain essentially unchanged. Thereafter, between the 7th and 20th postnatal days, peripheral auditory development proceeds rapidly, such that thresholds, tuning properties, temporal discharge patterns, and input/output functions achieve maturity. The role of synaptogenesis in the development of adult response properties has been studied through microionophoresis of neuroactive molecules onto the surface of neurons in the caudal divisions of the cochlear nuclei of developing kittens. Results of preliminary experiments suggest that inhibitory postsynaptic receptor function precedes intrinsic excitatory neurotransmission. Furthermore, during the first two weeks of postnatal development in kittens, GABA microionophoresis onto immature caudal CN neurons, exhibiting sustained responses to acoustic stimuli, converts response patterns to the onset type in the majority of neurons encountered.

Action Potentials↗

P2X receptor immunoreactivity in the rat cochlea, vestibular ganglion and cochlear nucleus.

P2X receptors have been reported to be involved in neurotransmission in both central and peripheral nerves. In the present study, polyclonal antibodies against P2X1, P2X2, P2X3, P2X4, P2X5, and P2X6 were used to study the distribution of P2X receptors in rat cochlea and vestibulocochlear nerve pathways. It was found that in the vestibular ganglion all six types of antibodies stained the neurons to different intensities. The strongest signal was obtained with the P2X2 antibodies, followed by P2X3 antibodies. The other four antibodies produced weak signals, of approximately the same intensity. In the spiral ganglion, the six types of antibodies also stained almost all neurons. However, the rank order of intensity was different from that in the vestibular ganglion: the strongest signal was still obtained with P2X2 antibodies, followed by P2X4, P2X1, and P2X3 antibodies. The immunolabelling was much weaker with P2X5, and P2X6 antibodies compared with the other four types of antibodies. In the cochlea, besides the spiral ganglion neurons, other tissues such as stria vascularis, the organ of Corti and the tectorial membrane were labelled intensively with P2X2 antibodies only. High density P2X2 immunoreactivity was also observed in the vestibulocochlear nerve fibres. In the cochlear nucleus, neurons and nerve fibres were stained with the P2X2 antibodies, as were the neurons in the trapezoid body. These results suggested that P2 receptors, especially the P2X2 receptors, may play important roles in the signal transduction involved in the perception of sound and balance.

Animals↗

Ultrastructural localization of GABA-immunoreactive terminals in the anteroventral cochlear nucleus of the guinea pig.

The immunocytochemical distribution of gamma-aminobutyric acid (GABA) was studied by electron microscopy in the anteroventral cochlear nucleus (AVCN) of the guinea pig using affinity-purified antibodies made against GABA conjugated to bovine serum albumin. Our observations confirm that spherical cells are the predominant cell type in the guinea pig AVCN and receive numerous axosomatic contacts (Schwartz and Gulley, (1978) J. Anat. 153, 489-508). Stellate cells receive few axosomatic contacts. Electron microscopic immunocytochemistry shows that GABA immunoreactivity is present in synaptic terminals in the AVCN. Of the several classes of presynaptic terminals present in the AVCN as characterized by vesicle type (large round; oval/pleomorphic; flat; small round) only those containing oval/pleomorphic vesicles were GABA-immunoreactive. However, GABA immunoreactivity may not be present in all these terminals because some oval/pleomorphic terminals are unlabelled. Immunoreactive terminals are widespread in the AVCN; they are abundant on spherical cell bodies, rarely seen on stellate cell bodies and are also found scattered throughout the neuropile.

Animals↗

Noradrenaline enhances temporal auditory contrast and neuronal timing precision in the cochlear nucleus of the mustached bat.

In the mustached bat, Pteronotus parnellii, noradrenaline (NA) was applied iontophoretically to single units in the anteroventral cochlear nucleus. NA suppressed tonic components of auditory responses and enhanced phasic onset responses to pure tone stimuli. The enhancement of onset activity was most pronounced in awake bats and was due to a decrease in the latency jitter of the first tone-evoked spikes from 0.55 msec in controls to 0.28 msec during NA application. In addition, NA reduced spontaneous neuronal activity. Noradrenergic antagonists suppressed phasic onset activity and increased the latency jitter of onset spikes. Opposite to the effect of NA, the tonic response component increased during application of the beta-antagonist propranolol but decreased during injection of the alpha 1-antagonist corynanthine. Other putative transmitter substances tested, nonselectively depressed both phasic and tonic response components (GABA, glycine) or increased both components either similarly or had more pronounced effects on the tonic response components (ACh, glutamate). Thus, NA specifically enhances auditory temporal contrast in favor of transients and improves neuronal timing precision, which may be of relevance for auditory tasks like passive sound localization, echolocation, and recognition of temporal patterns.

Acetylcholine↗

Descending inputs to the cat dorsal cochlear nucleus: an electron microscopic study.

This experimental study provides identification of several types of terminals in the fusiform cell layer (FCL) of the cat dorsal cochlear nucleus (DCN). Eight types of synaptic terminal were defined in control animals. 22 experimental cats were then subjected to unilateral lesions of the superior olivary complex or SOC (Groups I and II), the inferior colliculus or IC (Groups III and IV), or the IC plus the dorsal nucleus of the lateral lemniscus or DNLL (Groups V and VI). After one to 14 days, animals were killed by perfusion-fixation and brain stems prepared for light and electron microscopic study of degeneration. After SOC lesions, the ipsilateral FCL showed degeneration of small (type 2a) endings on small dendritic shafts; the contralateral FCL showed degeneration of larger (type 5) endings mostly on fusiform cell somata and on some primary dendrites. Both sides showed mild degeneration of large, glomerular (type 1a) endings. After small IC lesions, the ipsilateral FCL demonstrated degenerating type 1a glomerular endings but the contralateral FCL showed severe degeneration of type 5a terminals (axodendritic to fusiform cells) and mild degeneration of both glomerular (type 1a) and axosomatic (type 5) endings. Combined IC-DNLL lesions caused extensive degeneration in a pattern similar to that following IC lesions. In addition retrograde degeneration of fusiform cells occurred bilaterally. These studies showed that: (1) type 2a endings originate in the ipsilateral SOC; (2) type 5 endings on fusiform cell bodies originate from the contralateral SOC; (3) type 5a endings on fusiform cell dendrites originate from the contralateral IC; and (4) type 1a glomerular endings probably arise from several sources, including the IC, the SOC and (possibly) the DNLL of both sides.

Animals↗

Auditory evoked responses in the rat: transverse mastoid needle electrodes register before cochlear nucleus and do not reflect later inferior colliculus activity.

A previously described technique putatively differentiates short-latency auditory evoked potentials in peripheral and central neural pathways of the mouse and rat [Galbraith G, Waschek J, Armstrong B, Edmond J, Lopez I, Liu W, et al. Murine auditory brainstem evoked response: putative two-channel differentiation of peripheral and central neural pathways. J Neurosci Methods 2006;153:214-20]. This technique involves recording from orthogonally oriented subdermal needle electrode pairs, using fast sample rates (100k/s) to accurately measure differences in neural timing and waveform morphology. Electrodes oriented in a transverse plane (mastoid-to-mastoid) register an initial positive-going peak earlier than peaks recorded from electrodes oriented along the scalp midline (anterior and posterior to the interaural line). The absolute latency of the early mastoid component is consistent with an origin in the primary auditory nerve, while delayed midline latencies implicate activity in central neural pathways. We report here the results of recording simultaneously from transverse mastoid (M) needle electrodes and electrodes acutely implanted in cochlear nucleus (CN) and inferior colliculus (IC). The results show a highly consistent pattern in which the initial mastoid component leads CN by an average of 0.16 ms, suggesting an obligatory neural site of origin of the mastoid response that is distal to IC, namely the auditory nerve. Moreover, later IC components (beyond approximately 3.5 ms) are completely absent in mastoid recordings, indicating that the transverse mastoid recordings provide a relatively isolated measure of early auditory neural activity.

Acoustic Stimulation↗

Sensitivities of cells in anteroventral cochlear nucleus of cat to spatiotemporal discharge patterns across primary afferents.

1. This study tested the hypothesis that a cell in the anteroventral cochlear nucleus (AVCN) that receives convergent input from auditory nerve (AN) fibers can be sensitive to the temporal pattern of discharges on the set of AN fibers providing its input. 2. The temporal discharge pattern across the population of low-frequency AN fibers was manipulated by varying the phase spectra of complex stimuli that had fixed, flat magnitude spectra. By introducing a phase shift with variable slope at a particular frequency, the relative times of discharge of phase-locked neurons with different characteristic frequencies (CFs) could be varied. In this manner the overall spatiotemporal discharge pattern across the array of AN fibers was systematically manipulated. 3. Some low-frequency cells in the AVCN were sensitive to changes in the slope of the phase transition of the complex stimulus. The cells that were sensitive came from several different cell types in the AVCN. Their responses were consistent with the hypothesis that these cells were sensitive to the temporal relationships between discharges on their primary inputs and that they received inputs with different CFs, because the phase shifts introduced relative time differences between different frequencies. 4. Other cells were not sensitive to the degree of phase shift of the stimulus. This insensitivity implied either that these cells received inputs of the same, or nearly the same, CF, or that they were not sensitive to the time differences introduced by these changes in the phase spectra, or both. 5. The cells that were sensitive to the manipulations of the phase spectrum were located in the posterior region of anterior AVCN and in the posterior region of AVCN and thus were presumably either globular bushy, small spherical bushy, or stellate cells. No sensitive cells were located in the most anterior region of the AVCN, where large spherical bushy cells are located. 6. Temporal discharge patterns across the AN population in response to complex stimuli change as a function of level. Accordingly, the sensitivity of neurons to changes in the phase transitions of the complex stimuli used in this study was often affected by the level of the stimulus. 7. The sensitivity to changes in the phase spectrum was a frequency-specific effect. That is, a cell was most sensitive to changes made in phase that were centered near its CF and less sensitive to changes in phase that were introduced at frequencies below or above CF.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗