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The effect of the acoustic nerve chronic electric stimulation upon the guinea pig cochlear nucleus development.

14 newborn guinea pigs have been deafened three days after birth by bilateral destruction of the organ of Corti, and among them 8 have been supplied with a chronic auditory electric stimulation by means of an intracochlear implanted electrode. The histological study and the anatomical reconstructions of these animals' cochlear nuclei demonstrate that this chronic stimulation prevents, at least partially, these auditory pathway medullary formations from atrophy due to the cochlear destruction.

Animals↗

Reduction and recovery of neuronal size in the cochlear nucleus of the chicken following aminoglycoside intoxication.

The effect of aminoglycoside intoxication on the cross-sectional area of neurons in nucleus magnocellularis (NM) was studied in neonatal chickens. Birds received daily injections of 100 mg/kg body weight of gentamicin for 10 consecutive days. Cell area was measured at five different tonotopic regions along the posterior-to-anterior dimension of NM (low-to-high frequency) after post-treatment survival times of 8, 23 and 40 days. Gentamicin caused a reversible reduction of cell area that varied as a function of location and survival time. Significant decreases of cell area occurred only in the rostral half of the nucleus. Cell area was reduced at 8 and 23 days survival and recovered to near control values by 40 days post-treatment. Body weight, brain weight and the cross-sectional area of cerebellar Purkinje neurons were also reduced but did not recover. The present results show that aminoglycoside toxicity can affect auditory neurons in the brain. It is suggested that two factors contributed to the changes in NM neuron size: (1) Processes specifically related to the loss and regeneration of cochlear hair cells, most likely changes in afferent activity. (2) A general retardation in growth.

Animals↗

Projections of physiologically characterized globular bushy cell axons from the cochlear nucleus of the cat.

We made intraaxonal recordings from 30 individual globular bushy cell axons in the trapezoid body of the cat using HRP-filled glass microelectrodes. With subsequent HRP injection, we determined their axonal projection patterns. For cells with characteristic frequencies (CFs) above 3 kHz, short-tone peristimulus time histograms (PSTHs) at CF were typically primarylike at low tone intensities and primarylike with notch (PLN) or onset with low sustained activity (OL) at higher stimulus levels. Cells with CFs between 1 and 3 kHz showed the same response features with the spikes in the sustained region of the response phase-locked to the stimulus tone. Cells with CFs below 1 kHz showed phase-locked PSTHs with exceptionally high levels of synchrony compared to eighth nerve fibers with comparable CFs. This exceptional phase-locking was also noted when cells with CFs of 1-3 kHz were presented with tones below 1 kHz. Although the globular bushy cell axons were not completely filled from the soma of origin to terminal fields in the contralateral brainstem, a number of consistent anatomical features were distinguished in the population. All but one of the myelinated axons crossed the midline in the middle, large fiber component of the trapezoid body. Ipsilaterally, the axon always gave off from one to four collateral branches whose major targets were the posterior periolivary nucleus (PPO) and the lateral nucleus of the trapezoid body (LNTB). Minor termination sites for ipsilateral collateral branches were the dorsolateral periolivary nucleus (DLPO) and the lateral superior olive (LSO). Contralaterally the axon gave rise to one or two calyces of Held in the medial nucleus of the trapezoid body (MNTB). Three other major collateral branches arose from the contralateral axon and innervated a consistent set of areas. One headed caudally to innervate an area just ventromedial to the facial nucleus. Another followed the sixth nerve dorsally to innervate the dorsomedial periolivary nucleus (DMPO). A third collateral headed rostrally toward the ventral nucleus of the lateral lemniscus (VNLL), giving off occasional small sidebranches. Although each injected axon gave rise to a collateral that innervated the MNTB, it did not necessarily give rise to all three of the other collateral branches.

Action Potentials↗

Auditory brain stem of the ferret: some effects of rearing with a unilateral ear plug on the cochlea, cochlear nucleus, and projections to the inferior colliculus.

To examine the influence of acoustic experience on the development of the mammalian auditory brain stem, darkly pigmented ferrets were reared with a plug inserted in the right outer ear. The plugs were first inserted on postnatal day 23-34 and produced a variable, frequency-dependent attenuation of up to 60 dB. Between 3-15 months after the ear plug was begun, animals were prepared for physiological recording and injection of wheat germ agglutinin-HRP (WGA-HRP) in the left inferior colliculus (IC). The plug was removed and the condition of the right ear was assessed by pure-tone stimulation and recordings from neurons in the left IC. Neural audiograms for each animal showed a residual deficit in most cases. Following 24-60 hr survival, the animals were perfused and the right ear was examined. Brain-stem sections were reacted with tetramethylbenzidine. Outer and/or middle ear pathology was present in over half of the animals. However, the cochleas appeared to be normal and the spiral ganglion cells were normal by several quantitative criteria: number, area, and nucleolar eccentricity. The volume of each division of the cochlear nuclei (CN) and the areas of individual neurons in the anteroventral CN were the same on the right and left sides. The number of CN neurons retrogradely labeled from the left IC injection of WGA-HRP was found to be significantly increased in the left CN, relative to normal animals, when expressed as a ratio of the number labeled in the right CN. We conclude that the residual hearing loss in the previously plugged ears was predominantly or exclusively conductive. Neonatal, unilateral conductive hearing loss in the ferret does not lead to degeneration of the CN on the side of the loss, but it does lead to at least one rearrangement of auditory brain-stem connectivity. We suggest that the extent to which the brain stem is modified by early auditory deprivation is dependent on the type, degree, and symmetry of the hearing loss.

Animal Husbandry↗

Shared-stimulus driving and connectivity in groups of neurons in the dorsal cochlear nucleus.

Extracellular spike discharges were recorded from ensembles of up to five neurons simultaneously in the DCN of guinea pig using solid-state, thin-film, multichannel electrodes having up to five recording sites spanning up to 600 microns. Responses from 73 unit pairs were collected of which 54 had both units responding to pseudorandom wideband noise stimulation. Shared-stimulus driving was present in 78% (42/54) of the unit pairs and could be attributed to an overlap in their spectral sensitivities. Effective connectivity was indicated for 87% (47/54) of the unit pairs. Wideband noise proved more useful than tonebursts for investigating shared-stimulus driving and connectivity because it evoked widespread, but not overly synchronous, responses in the ensembles.

Acoustic Stimulation↗

Dynamic properties of the responses of single neurones in the cochlear nucleus of the rat.

1. The dynamic properties of unit responses to amplitude-modulated tones were studied using modulation with pseudorandom noise and described by cross-covariance and integrated cross-covariance functions between the discharge rate and the modulation. Under the experimental conditions used, these two functions are valid approximations of the system's impulse and step response functions respectively. 2. On the basis of their impulse response functions units could be classified into two groups, Type I with a low adaptation and Type II with a large degree of adaptation as well as a damped oscillation in their impulse response functions. 3. The response pattern of the Type II units is most likely the result of a negative feed-back striving to keep the discharge rate at a nearly constant level. 4. The cross-covariance functions are shown to remain unchanged during long duration recordings from the same unit.

Acoustic Stimulation↗

The kinetics of the response to glutamate and kainate in neurons of the avian cochlear nucleus.

Neurons in the nucleus magnocellularis (nMAG) of the chicken precisely transmit auditory nerve activity via glutamatergic synapses. Using techniques for rapid application of solutions, we have explored the properties of CNQX-sensitive glutamate receptors in whole cells and outside-out patches from the nMAG. Glutamate-evoked current in patches desensitized biphasically to less than 1% of the peak current, with a fast time constant of 960 microseconds at 22 degrees C, decreasing to 570 microseconds at 33 degrees C. Dose-response studies using kainate indicated that at least two agonist molecules bind to gate the channel. We propose a kinetic model that quantitatively describes our experimental observations. The rapid kinetics of this receptor are well suited to allow phase locking of synaptic signals to auditory stimuli.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

[Responses of neurons of the cat cochlear nucleus to 2-tone signals].

Two-tone stimuli were used with harmonic relation between their components (F1-F6). At equal intensities of the harmonics, one of which was the neuron best frequency and the other did not, evoke any impulse response, the neuron response as compared to that at the best frequency tone alone, was decreased in 50% of all cases, facilitated in 19% and not changed in 31% of cases. Harmonics nearest to the best frequency tone were most effective in the decreasing or increasing neuronal activity. With diminution of the intensity of the best frequency tone, F4 by 10-20 dB decreasing effects were less pronounced at all the side harmonics except F5, whereas facilitatory effects rose greatly at the lower harmonics F1-F3. Neuronal response, facilitatory or inhibitory, to a two-tone stimulus was also connected with the effects of the side harmonic on the neuron spontaneous activity and the neuron response value to F4. Statistical character of the relations observed seems to be due to the variety of interfering factors.

Animals↗

Changes in the synapses of spiral ganglion cells in the rostral anteroventral cochlear nucleus of the waltzing guinea pig following hair cell loss.

Between 10 and 60 days of age in the waltzing guinea pig, there is a genetically induced loss of all hair cells in the organ of Corti. About 43% of the spiral ganglion cells degenerate between 30 and 60 days of age. After 90 days of age, there is no further loss of spiral ganglion cells. Both Type I and II ganglion cells remain and are without afferent input. The terminals of these ganglion cells in the rostral AVCN, the end bulbs of Held, are normal until 30 days of age. During the period of ganglion cell loss degenerating end bulbs are seen. After 60 days of age, when most ganglion cell degeneration is complete, the remaining end bulbs have fewer synaptic vesicles and their synaptic junctions are flattened. The channels of enlarged extracellular space, which normally surround each synaptic junction or small groups of junctions, are only infrequently present. In freeze-fracture replicas of the rostral AVCN of waltzing guinea pigs after hair cell loss, the number of large, non-aggregate particles on the external leaflet of the principal cell opposite the end bulb is increased, and the number of perisynaptic aggregates is decreased compared to waltzing guinea pigs 10 days of age. The junctional aggregates are unaltered. These changes in the presynaptic terminal and postsynaptic membrane may be related to the loss of afferent input to the spiral ganglion cells, suggesting that activity is important for maintaining the synapse.

Age Factors↗

Membrane properties underlying the firing of neurons in the avian cochlear nucleus.

Neurons of the avian nucleus magnocellularis (NM) relay auditory information from the VIIIth nerve to other parts of the auditory system. To examine the cellular properties that permit NM neurons to transmit reliably the temporal characteristics of the acoustic stimulus, we performed whole-cell recordings in neurons of the chick NM using an in vitro thin slice preparation. NM neurons exhibited strong outward rectification near resting potential; the voltage responses to depolarizing current steps were substantially smaller than to equivalent hyperpolarizing steps. Suprathreshold current steps evoked only a single action potential at the start of the step. In contrast, stimulation with trains of brief current pulses evoked repetitive firing that was phase-locked to the stimulus cycle. The number of action potentials evoked by the pulses during the train decreased with increasing stimulus rate. Voltage-clamp experiments revealed a rapidly activating, slowly inactivating, outward current with a threshold near -65 mV. During depolarizing voltage steps, the outward current rose sigmoidally to a peak and then decayed slowly, reaching steady state within 5 sec. Application of 200 microM 4-aminopyridine (4-AP) reduced the peak of the outward current by 84%, leaving a small, persistent component. Under current clamp, application of 200 microM 4-AP reduced the outward rectification and increased the amplitude and duration of the action potentials. Moreover, NM neurons could no longer sustain firing during high rates of stimulation with the current pulses: increased temporal summation of the potentials caused sufficient depolarization to inactivate the sodium conductance underlying the action potential. These results suggest that the outward current is necessary for NM neurons to transmit well-timed events reliably for the duration of an acoustic stimulus.

4-Aminopyridine↗

Different phase sensitivity of low- and high-frequency neurons from the cat's cochlear nucleus.

When tested with two-tone signals while varying the phase value (omega 2) of the second harmonic, the low-frequency neurons (CFs from 0.8 to 5 kHz) showed one maximum and one minimum of the response value over the omega 2-range of 360 degrees. The high-frequency neurons (CFs from 11.5 to 38.5 kHz) showed two maxima and two minima under the same conditions. In addition, the high-frequency neurons, unlike the low-frequency ones, showed no difference in response to click series of opposite polarities. The data are considered in connection with processes of excitation in the low- and high-frequency regions of the cochlea.

Acoustic Stimulation↗

Speech perception with the ACE and the SPEAK speech coding strategies for children implanted with the Nucleus cochlear implant.

OBJECTIVE: The aim of this study is to determine whether implanted children using the ACE speech coding strategy demonstrate superior performances compared to implanted children using the SPEAK speech coding strategy over time. METHODS: Cochlear implanted children with prelinguistic sensorineural bilateral deafness of profound degree, using either the ACE or SPEAK coding strategy, were evaluated and compared. Both groups of children used one of the speech coding strategies continuously from the initial programming session and for a period of 2 years post-switch-on. One group comprised children who were retrospectively implanted and had received the SPEAK speech coding strategy (n=32) and the second group consisted of prospectively implanted children who received the ACE speech coding strategy (n=26). Both populations were homogenous as far as age of implantation, degree of hearing loss, anatomy of the cochlea, depth of electrode insertion, and educational and rehabilitative support provided. Children were assessed at 6, 12 and 24 months post switch-on via pure-tone audiometry and for speech perception tests. Children using the ACE speech coding strategy were additionally evaluated using the MAIS and MUSS language scales. RESULTS: Satisfactory benefits in speech perception were demonstrated by both groups of implanted children. No significant difference between the mean pure tone thresholds was observed postoperatively between the groups. Two years post switch-on the group using the ACE speech coding strategy demonstrated superior results for vowel discrimination in comparison to children using the SPEAK coding strategy. No significant difference was observed between the groups for performance on discrimination of syllable patterns (ESP) or for disyllablic word recognition tests. Additionally, the group of ACE users demonstrated maximum performance on MAIS and MUSS scales, 2 years post switch-on. CONCLUSIONS: The results clearly demonstrate significant benefit of cochlear implantation in prelinguistically deafened children for speech perception ability when using either the SPEAK or ACE speech coding strategies. Children using the ACE speech coding strategy demonstrate more rapid progress in improved speech perception ability initially, however 2 years post switch-on, no significant difference in performance on open-set speech recognition tests can be noted irrespective of the strategy in use.

Audiometry, Pure-Tone↗