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PubMed2000

Essential role of BETA2/NeuroD1 in development of the vestibular and auditory systems.

BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.

Acoustic Stimulation↗
PubMed1995

Influence of processing strategies on cochlear implant performance.

The development of new processing strategies has allowed for the improvement of auditory skills in cochlear implant recipients. This study examines the effects of a change in processing strategy on the individual recipients of the Nucleus cochlear prosthesis. Twenty-five subjects who had used the F0F1F2 processing strategy (WSP III) for 2 years were switched to the MPeak strategy (MSP) and retested immediately and after 3 months. Results revealed an improvement in speech recognition ability with the MPeak strategy in those subjects who were able to perceive speech with the F0F1F2 processing strategy.

Cochlea↗
PubMed1986

Projections from the cochlear nuclear complex to rhombencephalic auditory centers and torus semicircularis in the turtle.

The projections arising from the cochlear nucleus complex in the turtle were investigated using [35S]methionine as a tracer. Commissural connections between the auditory tubercles terminate in both the laminar and the magnocellular nuclei. The cochlear projections to the superior olivary complex, the lateral lemniscus complex and the torus semicircularis were predominantly contralateral. Terminal labeling in the torus semicircularis was found in the peritoral region (TSP) and in the central nucleus (TSC), particularly its caudoventral and rostromedial portions. The caudal dorsolateral portion of TSC, which had previously been shown to receive ascending spinal fibers was not labeled following injections of tracer into the cochlear nuclear complex. Ascending spinal and cochlear projections, however, appeared to overlap in the rostral portions of TSC and in TSP.

Animals↗
PubMed1980

Distribution and light microscopic features of granule cells in the cochlear nuclei of cat, rat, and mouse.

In the present study the cytology and the topography of the cochlear granule cell domain (a comprehensive term introduced here for all granule cell-containing regions of the cochlear nuclear complex) have been studied light microscopically in Nissl, Bielschowsky, and Golgi-Del Rio-Hortega material of cats, rats, and mice; in Golig rapid material of 0-14-day-old kittens; and in sections of 6-week-old kittens following HRP injections in the superficial dorsal cochlear nucleus (DCN). The domain has been parcellated in seven subdivisions which, in spite of some species' differences, are easily identifiable in all of the included animals. The cochlear granule cells are considered as a particular class of neuron, which is slightly different from, but nevertheless principally similar to the cerebellar granule cells in both shape and mode of neuronal connections. The digitiform terminals of the cochlear granule cells differentiate after the first two weeks of extrauterine life. In several respects these cells show larger variation among species than do the cerebellar granules, the similarity between the two classes of granule cells being most conspicuous in the rodent. The silver, Golgi rapid, and HRP material suggest that all, or at least the majority, of the granule cell axons project to the molecular layer of the DCN, forming parallel fibers similar to those of the cerebellar cortex. Also, the cochlear parallel fibers traverse the spiny apical dendrites of principal neurons (the pyramidal cells) and the smoother dendrites of molecular layer stellate cells.

Animals↗
PubMed2004

Role of auditory stimulation in maturation of the auditory pathway.

OBJECTIVE: To compare the maturation of the auditory pathway, as shown by electrical brainstem auditory potentials (EABRs), in ears with and without prior auditory stimulation. MATERIAL AND METHODS: Electrophysiological data were collected prospectively from ears which had received cochlear implants. Implant-evoked (Imp)EABRs were recorded. Thirty children, implanted after January 2000, were selected according to a strict inclusion/exclusion protocol. All the children had received a 22-channel Nucleus cochlear implant (CI24 series). Intraoperatively, ImpEABRs were recorded using the Medelec Synergy Evoked Response system in conjunction with Nucleus Neural Response Telemetry software. The ImpEABR latencies of waves eII, eIII and eV and the morphology of wave eV were assessed. RESULTS: ImpEABRs alter during the first 12 months of life. The latency becomes shorter during this period and the morphology of wave eV alters from a broad shape to a more distinct waveform. This appears to occur independently, even in the absence of auditory stimulation. CONCLUSION: The development of electrical brainstem auditory potentials is not dependent on auditory stimulation.

Acoustic Stimulation↗
PubMed1984

The fine structure of the lateral superior olivary nucleus of the cat.

The synaptic organization of the lateral superior olivary nucleus of the cat was analyzed under the electron microscope. The predominant cell type, the fusiform cell, has dendrites that extend from opposite poles of the cell body toward the margins of the nucleus, where they terminate in spinous branches. The fusiform cells are contacted by three types of synaptic terminals that can be distinguished by the size and shape of their synaptic vesicles. The somatic and proximal dendritic surfaces are apposed by synaptic terminals containing small, flat synaptic vesicles. Further from the cell body, the dendrites form numerous synaptic contacts with terminals containing large round vesicles as well as with the terminals containing small, flat vesicles. The most distal dendritic branches and their spiny appendages appear to form synapses almost exclusively with the terminals with large, round vesicles. A relatively rare type of terminal that contains small, round vesicles may form synapses with either the somatic or dendritic surfaces. A few small cells are interspersed among the fusiform cells, but they are more commonly located around the margins of the nucleus. The small cells form few axosomatic contacts. The simplest interpretation of the findings is that the terminals with small, flat vesicles arise in the medial nucleus of the trapezoid body and are inhibitory in function, whereas the terminals with large, round vesicles arise in the anteroventral cochlear nucleus and are excitatory; however, this remains to be demonstrated experimentally. In any case, the differential distribution of these two types of inputs on the somatic and dendritic surfaces must be an important determinant of the physiological response properties of the fusiform cells to binaural acoustic stimuli.

Animals↗
PubMed1995

Localization of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor mRNAs in rat brain.

Parathyroid hormone (PTH)-related peptide (PTHrP) has been identified in human tumors associated with the syndrome of humoral hypercalcemia of malignancy. PTHrP mRNA is also expressed in a variety of non-malignant tissues, suggesting that PTHrP is an endogenous peptide with as-yet unidentified autocrine or paracrine functions in normal tissues, including brain (Weir et al., Proc. Natl. Acad. Sci., 87 (1990) 108-112). In the present study, we used in situ hybridization to examine the expression of PTHrP and the common receptor for PTH and PTHrP in adult rat brain. Widespread yet anatomically discrete patterns of hybridization were observed using 35S-labeled antisense cRNA probes. PTHrP gene expression was highest in the supramamillary nucleus of the hypothalamus, medial superior olivary nucleus, and in subpopulations of cells in the neostriatum, hippocampus, and cerebral cortex. Other major sites of PTHrP gene expression included the amygdala, midline thalamic nuclei, pontine nuclei, choroid plexus, and the anterior pituitary gland. Highest levels of PTH/PTHrP receptor mRNA were in the mesencephalic portion of the trigeminal nucleus and the trigeminal ganglion, the lateral reticular, pontine and reticulotegmental nuclei, the hypoglossal nucleus and area postrema. Other major sites of PTH/PTHrP receptor expression included the anterodorsal nucleus of the thalamus, basolateral amygdala, entorhinal cortex, parasubiculum, cells in the Purkinje cell layer of the cerebellum, vestibular nuclei, ventral cochlear nucleus, the motor nucleus of the trigeminal, and the facial and external cuneate nuclei. The expression of genes encoding PTHrP and its receptor in discrete areas of the brain suggests that PTHrP may function as a neurotransmitter in the central nervous system.

Animals↗
PubMed1997

Effects of stimulus configuration on psychophysical operating levels and on speech recognition with cochlear implants.

Effects of electrode configuration and pulse duration on operating levels and on speech recognition performance were studied in a group of 14 adult postlingually deaf human subjects with Nucleus cochlear implants. The operating levels (based on detection threshold and maximum comfortable loudness levels) for narrowly spaced bipolar (BP) stimulation were found to be about 11 dB higher on average than those for widely spaced bipolar (BP+6) or monopolar (MP1) stimulation. Operating levels for common ground (CG) stimulation fell between those for BP and BP+6; the difference between BP and CG detection thresholds depended on pulse duration. Variation in detection thresholds and maximum comfortable loudness levels across the electrode array (electrodes 1-15) was larger for BP and CG stimulation than for BP+6 or MP1 stimulation, suggesting narrower spread of activation for the BP and CG configurations despite the higher current levels. Speech recognition performance was tested using experimental processor configurations. Among the experimental electrode configurations tested (BP, CG, and BP+6), the highest speech recognition scores were obtained with the BP+6 configuration in many subjects. Effects of pulse duration on speech recognition were less consistent and usually smaller than the effects of electrode configuration. The results indicate that electrode configuration is an important variable determining speech recognition performance and suggest that restriction of the size of neural population activated by individual channels of the prosthesis is not necessarily advantageous.

Adult↗
PubMed1977

Remodeling of neuronal membranes as an early response to deafferentation. A freeze-fracture study.

The early effects of deafferentation on the postsynaptic membrane beneath the end bulb of Held in the anteroventral cochlear nucleus (AVCN) were studied with the freeze-fracture technique. Three distinct responses were seen on the external membrane leaflet after cochlear ablation. Within 12 h the number of nonaggregate particles increased 147% by the addition of new particles to the membrane. The increase in number of nonaggregate particles continued until 4 days after cochlear ablation. The other responses occurred later, after degenerative changes were present in the end bulb. Between 1 and 2 days after cochlear ablation, the number of perisynaptic aggregates surrounding the postsynaptic active zone decreased to 10% of normal numbers. By 4 days, all perisynaptic aggregates had disappeared from the membrane. Coated vesicles may be involved in removing these aggregates. Between 1 and 3 days, the number of junctional aggregates decreased, but the size of the aggregates increased, apparently as a result of coalescence of nearby junctional aggregates. The total number of particles in junctional aggregates in the membrane was not altered during the first 6 days after cochlear ablation. The three separate responses suggest the existence of at least three different types of intramembranous particles on the external leaflet of the principal cell membrane, with each type dependent upon different cues for its maintenance in the membrane.

Afferent Pathways↗
PubMed1997

Effects of formant bandwidth on the identification of synthetic vowels by cochlear implant recipients.

OBJECTIVE: The main objective was to investigate whether the broadening and narrowing of formant bandwidths had a significant effect on the identification of vowels often confused by Nucleus cochlear implant recipients using the Spectral Peak (SPEAK) speech coding strategy. Specifically, identification performance for synthetic vowels with the first two formants (F1 and F2) parametrically varied in bandwidth was explored. DESIGN: Eight implanted subjects identified synthetic versions of the isolated vowel sounds [I, epsilon, lambda, [symbol: see text]] with F1 and F2 bandwidth manipulations, as well as foil tokens of [i, u, a, ae, [symbol: see text]]. Identification performance was examined in terms of percent correct as well as error patterns. Further analyses compared patterns of electrode activation. RESULTS: In general, broader F1 bandwidths yielded poorer performance and narrower F1 bandwidths yielded better performance relative to identifications for the reference stimuli. However, similar manipulations of F2 bandwidths resulted in less predictable performance. Comparison of electrode activation patterns indicated a distinct sharpening or flattening in the F1 frequency region for subjects with the greatest performance extremes. CONCLUSIONS: Manipulation of F1 bandwidth can result in concomitant changes in electrode activation patterns and identification performance. This suggests that modifications in the SPEAK coding strategy for the F1 region may be a consideration. Similar manipulations of F2 bandwidth yielded less predictable results and require further investigation.

Adolescent↗
PubMed1997

Neurons sensitive to interaural temporal disparities in the medial part of the ventral nucleus of the lateral lemniscus.

The ventral nucleus of the lateral lemniscus (VNLL) is implicated in processing monaural sounds, because its neurons receive input chiefly from the contralateral cochlear nucleus. However, we demonstrate here that a region of the VNLL contains a distinct population of neurons that process binaural sounds and are sensitive to interaural temporal disparities (ITDs). Responses of single neurons were recorded from unanesthetized rabbits by using metal electrodes or micropipettes loaded with dextran tagged with either biotin or a fluorescent label. Reconstructions of recording sites based on a few marks indicated that ITD-sensitive neurons were located in a medial region of VNLL that has a low density of neurons or in the adjacent reticular formation. In one animal the locations of five ITD-sensitive neurons were marked directly by injection of dextrans with different tags. All of these neurons lay in the medial region of the VNLL. The ITD-sensitive neurons of the VNLL had characteristic responses. Most neurons responded only at the onset of contralaterally or binaurally presented tones; many did not respond to ipsilateral stimulation alone and did not follow dynamic changes in the ITD. The presence of ITD-sensitive neurons in the VNLL that responded only at the onset of tones suggests that this center plays a role in the localization of transient sounds.

Acoustic Stimulation↗
PubMed1988

[Intraoperative electrophysiological monitoring for hearing preservation in acoustic neurinoma surgery].

Five acoustic neurinomas have been operated with hearing preservation as a goal. We monitored intraoperative brainstem auditory evoked potentials (BAEP) in all five cases, electrocochleogram (ECoG) using needle electrode in external auditory meatus in four, and compound action potentials directly recorded from the cochlear nerve (CAP VIII) in three. In all five cases the tumor was totally resected and cochlear nerve was anatomically preserved. However, in only one case useful hearing was preserved with preservation of all wave forms of the BAEP. Another patient with preservation of all wave forms of BAEP and the ECoG showed postoperative severe hearing loss. Other three patients showed postoperative severe hearing loss: only Wave I of BAEP and ECoG were preserved without preservation of the CAP VIII in one whose cochlear nerve was thought to be damaged in cerebellopontine angle cistern; Wave I of BAEP, ECoG and CAP VIII were preserved in one in whom it was suggested cochlear nerve near brainstem or cochlear nucleus was damaged; none of the BAEP, ECoG and CAP VIII was preserved in one in whom it was suggested distal cochlear nerve, or internal auditory artery was damaged. These different patterns of changes suggested that different causes for the hearing loss and difficulties in hearing preservation during acoustic neurinoma surgery. Having identified the putative mechanism of the hearing loss by monitoring those potentials, suggestions are made about how such hearing loss might be avoided. For preservation of the hearing in acoustic neurinoma surgery, all of those potentials including all wave forms of BAEP, ECoG and CAP VIII should be preserved during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Experience-independent development of dendritic organization in the avian nucleus laminaris.

The third-order auditory neurons of the avian nucleus laminaris (NL) have distinct dorsal and ventral dendritic tufts that receive their predominant synaptic input from, respectively, the ipsilateral and contralateral cochlear nucleus. Beginning about embryonic day (E) 14 in the chick and continuing for some weeks after hatching, NL neurons undergo a complex series of morphological transformations that result in the formation of a steep anteromedial-to-posterolateral gradient of increasing total dendritic length across the nucleus. This gradient perfectly parallels the tonotopic axis of NL. It has been proposed that acoustically evoked activity in the auditory pathway contributes importantly to formation of the gradient of dendritic length in NL and to several other features of dendritic development. The present experiment tested this hypothesis by surgically removing both otocysts (embryonic precursors of the inner ear) and studying the developing NL in the absence of peripheral input. The results of a quantitative study of Golgi-impregnated material show that at E17 both the steepness and predictability of the spatial gradient of dendritic length in operated animals are indistinguishable from normal. Similarly, the correlation of dorsal and ventral dendritic lengths on individual cells in operated animals is not significantly different from normal. The absolute length of both dendritic fields is reduced below normal, although only dorsal dendrites show a statistically reliable (14%) decrease. This is a significantly smaller effect than the 44% length reduction seen previously in animals with unilateral otocyst removal (T.N. Parks: J. Comp. Neurol. 202:47-57, '81); symmetrical afferent input appears more important to the regulation of NL dendritic length than the absolute level of this input.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Labile cochlear tuning in the mustached bat. II. Concomitant shifts in neural tuning.

Acoustic stimuli near 60 kHz elicit pronounced resonance in the cochlea of the mustached bat (Pteronotus parnellii parnellii). The cochlear resonance frequency (CRF) is near the second harmonic, constant frequency (CF2) component of the bat's biosonar signals. Within narrow bands where CF2 and third harmonic (CF3) echoes are maintained, the cochlea has sharp tuning characteristics that are conserved throughout the central auditory system. The purpose of this study was to examine the effects of temperature-related shifts in the CRF on the tuning properties of neurons in the cochlear nucleus and inferior colliculus. Eighty-two single and multi-unit recordings were characterized in 6 awake bats with chronically implanted cochlear microphonic electrodes. As the CRF changed with body temperature, the tuning curves of neurons sharply tuned to frequencies near the CF2 and CF3 shifted with the CRF in every case, yielding a change in the unit's best frequency. The results show that cochlear tuning is labile in the mustached bat, and that this lability produces tonotopic shifts in the frequency response of central auditory neurons. Furthermore, results provide evidence of shifts in the frequency-to-place code within the sharply tuned CF2 and CF3 regions of the cochlea. In conjunction with the finding that biosonar emission frequency and the CRF shift concomitantly with temperature and flight, it is concluded that the adjustment of biosonar signals accommodates the shifts in cochlear and neural tuning that occur with active echolocation.

Acoustic Stimulation↗
PubMed1993

Expression of Fos in rat central nervous system elicited by afferent stimulation of the femoral nerve.

To investigate the distribution of Fos-like immunoreactivity (FLI) in the central nervous system of urethane anesthesized rats after activation of a somatosympathetic reflex pathway, the cut central end of the right femoral nerve of 17 male Wistar rats was stimulated electrically for 1 h at parameters such that increases in heart rate and arterial pressure were elicited. Sections of brain and spinal cord were incubated in anti-Fos antibody and the presence of FLI was detected using the ABC immunoperoxidase method. In the spinal cord FLI was present in the ipsilateral lumbar spinal cord (laminae 1 and 2, 4-6 and 10) and contralateral intermediolateral nucleus in the thoracic spinal cord. In the hindbrain, FLI was present in the contralateral rostral ventrolateral medulla and bilaterally in the cochlear nucleus, external cuneate nucleus, locus coeruleus and lateral parabrachial nucleus. In the midbrain, label appeared in the Edinger-Westphal nucleus and peripeduncular nucleus on both sides. In the forebrain, FLI appeared bilaterally in the central nucleus of the amygdala, para- and periventricular hypothalamus, supraoptic nucleus, paraventricular thalamus, reuniens nucleus, subfornical organ and bed nucleus of the stria terminalis. These results define the central nervous system pathways of somatosympathetic reflexes and demonstrate that areas in the forebrain not previously known to be activated by somatosympathetic reflexes, but previously implicated in mediating the defense reaction, are activated by these reflexes.

Afferent Pathways↗
PubMedDate not supplied

Tinnitus: diagnosis and treatment.

Few conditions are seen as commonly by the otologist and are more poorly understood than subjective tinnitus. Tinnitus has been reported in as high as 80% of patients seen in an otolaryngology practice. This symptom is especially marked in patients with a hearing problem and can be so severe that it becomes incapacitating. Careful diagnosis and classification of tinnitus is important for understanding of the problem. Identification of the frequency and intensity of masking, using a tinnitus analyzer, is useful in selecting the form of treatment. Analysis of the history, physical findings and the use of special electrocochleography and brain stem evoked response audiometry help to identify the site of lesion, which may be within the cochlea, cochlear nerve, cochlear nucleus, brain stem, midbrain or auditory cortex. Specific disease entities should be identified and treated. Lesions of the end-organ or cochlear nerve can be treated when necessary by translabyrinthine or middle cranial fossa section of the cochlear nerve. Tinnitus from cervical nerve lesions can be treated by rhizotomy. The use of a hearing aid or introduction of a sound with a tinnitus masker has been found to be 82% effective in suppressing tinnitus. Maskers can be combined with a hearing aid in some cases. The pathogenesis of tinnitus is discussed, but the method of action of tinnitus relief by auditory stimulation is still unclear. A thoughtful and complete examination with our new diagnostic tools and the judicious selection of therapy now makes it possible to give relief to the majority of patients suffering with disturbing tinnitus.

Adult↗
PubMed1983

Frequency-specific projections of individual neurons in chick brainstem auditory nuclei.

Nucleus magnocellularis and nucleus laminaris in the avian brainstem contain second- and third-order auditory neurons thought to be homologous to the mammalian anteroventral cochlear nucleus and medial superior olivary nucleus, respectively. Nucleus laminaris in the chicken is a tonotopically organized sheet of bipolar neurons; each of these neurons receives spatially segregated bilateral innervation from the two magnocellular nuclei. In the present study, this projection was studied at the single cell level by analyzing the pattern of terminal arborizations of individual horseradish peroxidase-filled axons. Reconstruction of the terminal arborizations of nucleus magnocellularis axons revealed that each axon forms an elongated band of endings, the long axis of which is parallel to the physiologically defined isofrequency bands. Within a band, the individual terminal collaterals form distinct patches separated by areas without endings. We suggest that the elongated terminal fields provide the basis of the tonotopic organization observed in nucleus laminaris and that the trajectories of the ipsilateral and contralateral axons may provide differential conduction delays that are important for binaural integration of acoustic information.

Animals↗
PubMed1991

Independent evaluation of the speech perception abilities of children with the Nucleus 22-channel cochlear implant system.

The performance of 28 children with the Nucleus multi-channel cochlear implant, who had used the device an average of 1.7 yr, was examined on a battery of speech perception measures. All children demonstrated better speech perception skills with the implant than they had in the preimplant condition with hearing aids. With the Nucleus implant, 61% of the children demonstrated some open-set speech recognition and another 14% demonstrated closed-set speech recognition. Scores on the tests were corrected for guessing and a hierarchy of test difficulty was developed. The results revealed systematic differences in performance as a function of perception task and test format. The results of regression analyses, which were performed to identify predictors of success, showed that communication mode made a significant unique contribution to the variance in performance among subjects on an open-set word recognition test. When the scores of the children who used oral or total communication were compared on the full battery of tests, however, there were few significant group differences.

Adolescent↗

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