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Myelin-deficiency in the cochlear nerve of the 'bt' mutant hamster.

In a previous report, we showed abnormal auditory evoked potentials in the mutant hamster, 'black tremor (bt)', with significantly prolonged wave latencies of auditory brainstem responses and prolonged N1 latencies of compound action potentials, but normal cochlear microphonics. In this report, we present the results of morphological studies supporting the results of our electrophysiological studies of the auditory pathway in bt. Observation by transmission electron microscopy revealed an abnormal myelin sheath surrounding the spiral ganglion cells, and a thinner compact myelin sheath surrounding the axons in bt than in normal hamsters. The bt hamster has a myelin deficiency not only in the brainstem, but also in the cochlear nerve.

Animals↗

Cochlear nerve fiber responses to amplitude-modulated stimuli: variations with spontaneous rate and other response characteristics.

1. Single-fiber responses to sinusoidally amplitude-modulated (AM) tones were recorded from the cochlear nerves of anesthetized guinea pigs. Stimuli were presented at the fiber's characteristic frequency (CF) and covered the intensity range between the fiber's minimum rate threshold and 90-100 dB SPL in 5- or 6-dB steps. The amount of modulation in each fiber's response and the average rate of the responses were quantified. The observed response modulation was compared with the modulation to be expected on the assumption that the instantaneous discharge rates varied with intensity in the same way that the average rates did (i.e., as predicted from each fiber's average-rate vs. level function). 2. The difference between the observed and expected response modulation varied widely across fibers. In most fibers' the responses to a limited range of stimulus intensities (typically between 20 and 30 dB above the fiber's rate threshold) were modulated far more than expected on the basis of their average rates, with responses to stimuli either above or below this range differing progressively less from expectation. Little or no response modulation was observed above approximately 70 dB SPL in these fibers. Other fibers exhibited response modulation that exceeded the expected modulation by smaller amounts, but maintained this modulation to much higher sound pressure levels. 3. The discrepancy between the observed and expected responses to AM stimuli also varied with the frequency of modulation (fm) within individual fibers. The discrepancies were least pronounced at low fms (e.g., 10 Hz) but became progressively larger as fm was increased to between 50 and 320 Hz (subject to the inter-fiber variations described in 2, above). 4. The AM response characteristics varied systematically with the fiber's spontaneous rate and other response characteristics (e.g., rate threshold, CF rate vs. level function type, and rapid adaptation characteristics). In particular, the most sensitive, high spontaneous rate fibers had responses that adapted rapidly after the onset of a stimulus, and showed the greatest enhancement of AM-related information at low-to-moderate stimulus intensities. However, these fibers appeared incapable of encoding AM-related information at high intensities, since their response rates "saturated" and their AM response enhancements diminished around 30 dB above threshold. In contrast, the less sensitive (i.e., higher threshold), lower spontaneous rate fibers showed less evidence of rapid adaptation near the onsets of their response, and lesser enhancements of the modulated responses predicted from their average-rate versus level functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Transitional expression of OX-2 and GAP-43 glycoproteins in developing rat cochlear nerve fibers.

The OX-2 and GAP-43 glycoproteins are two proteins involved in neuronal cell-to-cell interaction and/or growing of dendrites and axons. Therefore, for the auditory receptor the expression of these proteins could provide information on the afferent and efferent nerve fiber organization. The expression and distribution of OX-2 and GAP-43 were analyzed during the auditory receptor development and maturation (from embryonic day E13 to postnatal day P22). Both glycoproteins were early recognized in the cochleae of E13 rats. Then, they slowly but progressively disappeared, being absent when the animals reached the P22 postnatal day. At E13, a weak OX-2 expression was restricted to the perikaryon of the spiral ganglion neurons, while in the same period a strong GAP-43 immunostaining was found in both the neuronal perikaryon and the neurites. During the rat embryonic period (E13 to birth) the expression of both glycoproteins appeared progressively restricted to the neurites. During the rat postnatal period (P0 to P22), OX-2 and GAP-43 exhibited a dissimilar distribution pattern. The OX-2 glycoprotein appeared in the afferent, efferent and fibers of the auditory nerve, while the GAP-43 glycoprotein only appeared in the efferent nerve fibers. Present data suggest that OX-2 and GAP-43 could act as two complementary glycoproteins during the development, organization, and maturation of the cochlear nerve fibers. While both glycoproteins could participate in axonal growing and orientation, OX-2 could also be involved in a similar process for auditory dendrites.

Animals↗

Auditory brainstem implant in posttraumatic cochlear nerve avulsion.

Patients aged over 12 years with neurofibromatosis type 2 are considered candidates for an auditory brainstem implant (ABI). This study extends the indication criteria of ABI to subjects with profound hearing loss due to damaged cochleas and/or cochlear nerves (CNs) following head injuries. In our department, over the period from April 1997 to November 2002, 32 patients, 23 adults and 9 children, were fitted with ABIs. Their ages ranged from 14 months to 70 years. These patients were suffering from a variety of tumor (13 subjects) and nontumor CN or cochlear diseases (19 subjects). Six patients, 5 adults and 1 child, had profound hearing loss following head injury. Their mean age was 25 years (range: 16-48 years). Five were male and 1 female. The retrosigmoid approach was used in all 6 patients. The electrode array was inserted into the lateral recess of the fourth ventricle and correct electrode positioning was monitored with the aid of electrically evoked auditory brainstem responses and neural response telemetry. Correct implantation was achieved in all patients. No complications were observed due to implantation surgery or related to ABI activation and stimulation of the cochlear nuclei. At activation, an average of 9.8 electrodes (range 5-13) were switched on without side effects. One to 6 electrodes were activated in the following sessions after time periods ranging from 2 to 16 months. All patients achieved auditory-alone-mode closed-set word recognition scores ranging from 40 to 100%; 3 had auditory-alone-mode open-set sentence recognition scores of 60-100%; 2 of these even had speech-tracking performance scores of 38 and 43 words, respectively, showing an ability to engage in normal conversation and converse over the phone. The present study demonstrates that the ABI is a useful rehabilitation instrument in subjects with damaged cochleas and/or CN avulsion following head injury who are unamenable or poorly responsive to auditory rehabilitation using cochlear implants.

Adolescent↗

[Intraoperative monitoring of hearing function in the removal of cerebellopontine angle tumor: auditory brainstem response and cochlear nerve compound action potential].

Intraoperative hearing monitoring may be the best approach for hearing preservation in the removal of cerebellopontine angle (CPA) tumors. We designed an intracranial electrode for a reliable and consistent recording of the cochlear nerve compound action potential (CNAP), and compared the efficiency of the CNAP and auditory brainstem response (ABR) while monitoring the CPA tumor removal. Simultaneous intraoperative monitoring of CNAP and ABR were performed in 7 patients with CPA tumors (5 acoustic neurinomas and 2 epidermoids) undergoing tumor removal aimed at hearing preservation. We designed an intracranial electrode for CNAP monitoring made of a fine malleable insulated wire with a tiny tuft of oxidized cellulose on the tip. Postoperatively, the hearing of 6 patients was preserved. Useful hearing was preserved in 5 of those. ABR recordings were unsatisfactory because of severe artifacts during the tumor removal. It was discernible only in 2 of the 7 patients. Postoperatively, useful hearing was preserved in the 2 patients with a discernible ABR during the tumor removal. Four of 5 patients with no discernible ABR during the tumor removal preserved hearing. Before the tumor removal, all patients showed a reproducible CNAP of an amplitude 20 times larger than the amplitude of ABR without artifacts. A reliable CNAP was recorded consistently throughout the tumor removal in 5 patients, in whom useful hearing was preserved postoperatively. CNAP disappeared completely during the tumor removal in 1 patient who lost hearing postoperatively. Because of severe artifacts and poor specificity, the intraoperative ABR monitoring can not predict the postoperative hearing condition. Our newly designed intracranial electrode enables consistent CNAP recording during tumor removal. CNAP reflects the effect of surgical manipulations on hearing and predicts the postoperative hearing condition. CNAP is a more efficient form of intraoperative monitoring than ABR during CPA tumor removal.

Action Potentials↗

Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

Action Potentials↗

Phase-locking in the cochlear nerve of the guinea-pig and its relation to the receptor potential of inner hair-cells.

The high-frequency limit of phase-locking has been measured in fibres of the auditory nerve in the guinea-pig. It is shown that phase-locking begins to decline at about 600 Hz and is no longer detectable above 3.5 kHz which is about 1 octave lower than in the cat, squirrel monkey and some birds. Direct measurements of the cochlear afferent fibre synaptic delay are consistent with indirect estimates from phase-locking, both giving values of 0.7-0.8 ms. Measurements of the receptor potentials of inner hair-cells in the guinea pig cochlea indicate that as the stimulus frequency is increased there is a progressive decrease in the a.c. component compared to the steady depolarization. The cause of this decline is the low-pass filtering of the a.c. component by the hair-cell membrane. The cut-off and slope of the decline in the a.c. component is consistent with the suggestion that this process is the limiting factor in cochlear nerve fibre phase-locking. The implications of these findings for interspecies variation in phase-locking cut-off, for cochlear mechanisms and for the encoding of complex sounds are discussed.

Acoustic Stimulation↗

Electrical stimulation of the cochlear nerve in deafness mice.

The deafness mouse mutant provides a useful animal model for studying the central consequences of complete auditory deprivation during development. The object of this study was to record inferior colliculus-evoked potentials in mutant and control mice, using short electrical pulses to stimulate either the whole cochlea or the cochlear nerve directly. In both experiments, evoked potentials were readily recorded in the mutant and control mice, indicating that some central connections are functional, even though the auditory pathway has received no stimulus-related input throughout development. The results are relevant to the clinical problem of restoring auditory function in the profoundly deaf using peripheral electrical stimulation.

Animals↗

Polarity order of biphasic square pulse electric current stimulation of human cochlear nerve: observations with transtympanic electrodes.

Eighteen totally deaf human cochleae were stimulated with biphasic square pulses of current through transtympanic needle electrodes. The thresholds of the 2 polarity orders, + - and - +, were compared for various pulse durations. For a pulse duration of 500 microseconds the polarity order - + had the lower threshold. For pulse durations of 2 ms and longer, the polarity order + - had the lower threshold. A discussion is given of the significance of the results for finding out the site of cochlear nerve excitation by the stimuli.

Cochlear Nerve↗

Mechanism of vasodilation by cochlear nerve stimulation. Role of calcitonin gene-related peptide.

Rabbit aortic rings pre-contracted with 1 microm phenylephrine were exposed to organ fluid of isolated guinea pig cochleas which had been subjected to electrical field stimulation (FS, 50 Hz, 50 V, 0.2 ms over 2 min). This resulted in an endothelium-dependent relaxation of the vessel rings sensitive to glibenclamide, an ATP-sensitive K+channel blocker. Tetrodotoxin (1 microm) added to the cochlear fluid blocked the vasorelaxant effect of cochlear FS and it attenuated vasorelaxation when added to aortic rings. The relaxation response paralleled an increase in the level of calcitonin gene-related peptide (CGRP) in both cochlear and vascular organ fluids from undetectable pre-stimulation values to 0.12+/-0.029 and 0.44+/-0.051 n m, respectively. We conclude that CGRP possibly contributes to cochlear nerve stimulation-induced endothelium-dependent vasorelaxation.

Animals↗

Sharply tuned cochlear nerve ensemble periodicity responses to sonic and ultrasonic frequencies.

Vertebrates are able to perceive the pitch of a series of harmonics, even when the fundamental frequency has been removed from the acoustic stimulus. Neural periodicity responses corresponding to the "missing fundamental" frequency of sonic stimuli have been observed in the auditory system of several animal species, including our own. This paper examines periodic cochlear neural responses of the gerbil. Periodicity responses to both sonic and ultrasonic stimuli originate within the cochlea of this animal. Acoustic stimuli, consisting of 2-12 successive harmonic frequencies, were used to generate an ensemble cochlear nerve periodicity response that was recorded from the round window of the cochlea. This response had a frequency equal to that of the missing fundamental, and not to those of the harmonic stimuli. Forward masking of the stimuli used to produce the periodicity response was used to generate sharp tuning curves, with tip frequencies corresponding to the harmonics and not to the periodicities. The sharpness of these functions increased as the frequencies of the harmonics increased, up to at least 38 kHz. This property could be related to reception of ultrasonic vocalizations utilized by many rodent species.

Acoustic Stimulation↗

Noise improves transfer of near-threshold, phase-locked activity of the cochlear nerve: evidence for stochastic resonance?

Stochastic resonance can be described as improved detection of weak periodic stimuli by a dynamic nonlinear system, resulting from the simultaneous presentation of a restricted dynamic range of low-intensity noise. This property has been reported in simple physical and biological activities. The present study describes data consistent with the interpretation that stochastic resonance can be observed in the response of cochlear neurons. These experiments utilized low levels (-5 to 25 dB SPL) of stimuli and noise (5 to 30 dB SPL). Stimuli consisted of simultaneously presented 8 kHz (F1) and 8.8 kHz (F2) tone bursts, which generated an 800 Hz F2-F1 cochlear nerve envelope ensemble response in the gerbil. The mean response threshold was approximately -3 dB SPL. Simultaneous presentation of a low-intensity wideband noise increased the amplitude of this response. This was observed with tonal stimuli having intensities of 0-5 dB SPL; responses to stimulus levels > 10 dB were attenuated by noise. Response amplitude was increased by noise levels of 10-15 dB; the amplitude was unaffected by lower levels of noise, and decreased in the presence of higher noise levels. These properties are compatible with those of stochastic resonance.

Acoustic Stimulation↗

The development of stimulus following in the cochlear nerve and inferior colliculus of the mouse.

The decrement of evoked response amplitudes during the presentation of repetitive clicks was examined quantitatively at the level of the eighth nerve and inferior colliculus in mice aged 13-60 days postnatal. The amplitudes of both these potentials were found to decline during the course of stimulation, this being much more severe at the onset of hearing than in adults. Furthermore the following response at the level of the cochlear nerve was adult-like by day 18, while the response at the level of the inferior colliculus continued to improve through day 24. Recordings in the inferior colliculus were consistently obtained in two different regions along the frequency axis. The regions that responded best to a lower range of frequencies (e.g. 3-9 kHz) showed a more rapid and severe decrement in the evoked response to repetitive stimulation than those regions responding best to a higher range of frequencies (e.g. 8-17 kHz). This was found to be the case for repetitive click stimuli and repetitive tone bursts. Single unit responses in the inferior colliculus were consistent with this differential decline as a function of stimulus rate seen along the frequency axis.

Age Factors↗

Fine structure of the cell clusters in the cochlear nerve root: stellate, granule, and mitt cells offer insights into the synaptic organization of local circuit neurons.

The small cell shell of the cochlear nucleus contains a complex integrative machinery which can be used to study the roles of interneurons in sensory processing. The cell clusters in the cochlear nerve root of the chinchilla provide the simplest example of this structure. Reported here are the neuronal architecture and synaptic organization of the three principal cell types and the three distinctive neuropil structures that could be characterized with the Nissl and Golgi methods and electron microscopy. Granule cells were characterized by several dendrites with claw-like terminals that received synaptic contacts from multiple excitatory mossy fiber rosettes. Given their relatively large number and their prolific parallel fiber synapses, the granule cells provide a suitable substrate for a tangential spread of excitatory activity, which could build to considerable proportions. The mitt cells had a thickened, single dendrite, its terminal branches arranged in a shape reminiscent of a baseball catcher's mitt. The dendritic mitt enclosed an enormous, convoluted mossy fiber rosette forming many excitatory synapses on just one cell. This could provide for a discrete, comparatively fast input-output relay of signals. Small stellate cells had longer, radiating dendrites that engaged the synaptic nests. These nests were strung in long strands, containing heterogeneous synapses from putative excitatory and inhibitory inputs. Given the prevalence of the synaptic nests, the small stellate cells appear to have the greatest integrative capacity. They provide the main output of the synaptic nests.

Animals↗

Functional correlates of characteristic frequency in single cochlear nerve fibers of the Mongolian gerbil.

Single-unit recordings obtained from the auditory nerve of the Mongolian gerbil, Meriones unguiculatus, revealed functional differences in the response properties of neurons tuned to low and high frequencies. The distribution of neural thresholds displayed a distinct rise for auditory nerve fibers with characteristic frequencies (CFs) between 3-5 kHz. This frequency band also marked abrupt changes in both the distribution of spontaneous discharge rates and the shape of the neural tuning curve. For neurons of all CFs, spontaneous firing rates were inversely related to neural threshold but unrelated to sharpness of neural tuning. The range of CF thresholds encountered, even when data from many animals were combined, rarely exceeded 20 dB, suggesting that cochlear nerve responses obtained from this species display little inter-animal variability. These results are compared with similar data from other species and discussed in terms of recent studies on sound communication and cochlear anatomy in gerbils.

Animals↗

Cochlear nerve acoustic envelope response detection is improved by the addition of random-phased tonal stimuli.

We test Lowenstein's dc bias hypothesis as an alternative mechanism for the phenomenon sometimes called 'stochastic resonance'. Probe stimuli consisting of paired phase-locked tones at frequencies f(1) and f(2) (where f(2)-f(1)=800 Hz, f(1)>4.5 kHz) and at equal intensity were used to generate synchronous 800 Hz cochlear nerve activity (envelope responses). When a background tone of the same intensity, with a frequency halfway between f(1) and f(2), is presented simultaneously with the probe stimulus, the envelope response amplitude typically decreases. Consistent with Lowenstein's hypothesis, however, when the intensities of the probe and background tone are near the detection threshold of the envelope response (approximately 0-20 dB sound pressure level), the simultaneous presence of the background tone often increases the amplitude of the envelope response. At these same intensity levels, when the background tone precedes the probe stimulus, it decreases the amplitude of the response to the probe stimulus. The effects of simultaneous presentation of the probe and the background tone are frequency-dependent, becoming less pronounced or reversing as the frequency of the background tone departs from those of the probe stimuli.

Acoustic Stimulation↗