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Outward currents in isolated ventral cochlear nucleus neurons.

Neurons of the ventral cochlear nucleus (VCN) perform diverse information processing tasks on incoming activity from the auditory nerve. We have investigated the cellular basis for functional diversity in VCN cells by characterizing the outward membrane conductances of acutely isolated cells using whole-cell, tight-seal, current- and voltage-clamp techniques. The electrical responses of isolated cells fall into two broad categories. Type 1 cells respond to small depolarizations with a regular train of action potentials. Under voltage clamp, these cells exhibit a noninactivating outward current for voltage steps positive to -35 mV. Analysis of tail currents reveals two exponentially decaying components with slightly different voltage dependence. These currents reverse at -73 mV, near the potassium equilibrium potential of -84 mV, and are blocked by tetraethylammonium (TEA). The major outward current in Type I cells thus appears to be mediated by potassium channels. In contrast to Type I cells, Type II cells respond to small depolarizations with only one to three short-latency action potentials and exhibit strong rectification around -70 mV. Under voltage clamp, these cells exhibit a noninactivating outward current with a threshold near -70 mV. Analysis of tail currents reveals two components with different voltage sensitivity and kinetics. A low-threshold current with slow kinetics is partly activated at rest. This current reverses at -77 mV and is blocked by 4-aminopyridine (4-AP) but is only partly affected by TEA. The other component is a high-threshold current activated by steps positive to -35 mV. This current is blocked by TEA, but not by 4-AP. A simple model based on the voltage dependence and kinetics of the slow low-threshold outward current in Type II cells was developed. The model produces current- and voltage-clamp responses that resemble those recorded experimentally. Our results indicate that the two major classes of acoustic response properties of VCN neurons are in part attributable to the types of outward (potassium) conductances present in these cells. The low-threshold conductance in the Type II (bushy) cells probably plays a role in the preservation of information about the acoustic stimulus phase from the auditory nerve to central auditory nuclei involved in low-frequency sound localization.

4-Aminopyridine↗

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↗

[Structural and functional state of the erythrocyte membrane in experimental carcinogenesis].

Structural and functional state of erythrocyte surface membrane was studied in C3H and C57B1/6 mice as well as in Wistar rats after 20-methylcholanthrene administration. It is shown that mice genetically susceptible to tumor growth as compared with mice resistant to carcinogenesis are characterized by an increased level of spinous erythrocytes (echinocytosis), higher membrane microviscosity and a tendency to increase polarity of their membrane lipid bilayer in the region of hydrophobic spine sound localization. The growth of chemically induced sarcomas was also accompanied by echinocytosis but with opposite changes in microviscosity and polarity of the erythrocyte membrane lipid bilayer. It is supposed that spinous erythrocyte transformation induced by different causes is based on different physicochemical factors.

Adenosine Triphosphatases↗

Auditory and academic performance of children with unilateral hearing loss.

Since the data provided in the literature concerning unilateral hearing loss in children are still lacking, we decided to study a group of subjects suffering from unilateral sensorineural deafness that has developed during the first 12 years of life. One hundred and fifteen subjects out of 150 answered a questionnaire that intended to investigate at what age the disorder developed, how it was recognized, its possible causes and a subjective evaluation of the difficulties encountered because of the hearing deficiency. In a second stage of the research, more detailed case history data were obtained on 30 children who satisfied more stringent selection criteria. The same children were compared with a matched control group of 30 normal hearing subjects, on speech in noise recognition, and sound localization skills. Results were correlated with the academic and educational progress and case history data. Our results may demonstrate that unilateral deafness represents a far from negligible handicap concerning the child's learning and relationship with classmates and teachers, specially during compulsory school life.

Adolescent↗

Binaural characteristics of units in the owl's brainstem auditory pathway: precursors of restricted spatial receptive fields.

The barn owl uses binaural phase and intensity differences for sound localization. These two cues also determine the receptive fields of specialized neurons in the inferior colliculus. The main aim of this study was to investigate where neuronal sensitivity to the binaural cues emerges in the brainstem auditory nuclei, and how this sensitivity reaches the neurons in the inferior colliculus. The owl's phase-sensitive neurons are selective to microsecond phase differences of high frequency signals, unlike mammalian phase-sensitive neurons which are restricted to low frequency signals. In certain nuclei virtually all of the neurons are sensitive to either phase differences or intensity differences, but not to both. These nuclei form two distinctly separate pathways that converge at the inferior colliculus where neurons selective to both phase and intensity differences occur. In contrast to the mammalian auditory system, the owl's phase- and intensity difference-sensitive pathways are not segregated into low frequency and high frequency channels.

Acoustic Stimulation↗

The avian stapedius muscle. Influence on auditory sensitivity and sound transmission.

The influence of the solitary avian middle ear muscle, the m. stapedius, on auditory sensitivity and sound transmission was investigated in the domestic chicken, Gallus gallus. Electrophysiological recordings of inner ear microphonic potentials (MP) were made in order to determine the effects of calibrated, mechanically induced stapedius muscle (SM) tension changes on sounds reaching the auditory receptor cells. The maximum MP responses recorded during the pre-tension measurements were on the order of 200 microV and were linear (on a log-log scale) over a range of 40-100 dB SPL. Tension levels of 50-400 mN in the SM caused a reduction of up to 20 dB in the MP at frequencies throughout the auditory spectrum. It is concluded that the SM of Aves serves to protect the inner ear receptor cells against overstimulation. In addition to attenuating the amplitude of the MP response, SM tension changes caused significant changes in the phase of the signals reaching the inner ear. The magnitude of attenuation in the ipsilateral MP response to 200-400 mN of tension was found to be similar to the interaural attenuation that occurs when sound is transmitted to the ipsilateral ear from the contralateral ear via the intracranial passageway. The similarity in MP amplitude changes resulting from SM tension and intracranial transmission suggests that the SM may be involved in interaural interaction and thereby may aid in sound localization.

Animals↗

Effector pattern of the audio-visual targeting reflex in cats.

The development of the effector pattern of the unconditioned and instrumental conditioned audio-visual targeting reflex was studied. EOG and EMG electrodes were implanted to analyze the movements of the pinna, eye and head, when the animals localized a sound source placed in different positions in space. When the acoustic stimulus was repeated, the unconditioned targeting reflex was characterized by a rapid intra- and intersessional habituation of the three motor components. In the second part of the experiment the unconditioned targeting reflex was reinforced by food to build up an instrumental conditioned targeting reflex. It was shown, that under both experimental conditions the targeting reflex began with the auricular component, followed by the oculo-cephalic response. After conditioning the latencies were decreased in comparison with the unconditioned reactions. The shortest latencies and most stable responses were found in the pinna muscles ipsilateral to the sound source. After conditioning the resistance to extinction was increased for all three motor components, but the pinna movement ipsilateral to the sound source was again the component most resistant to extinction.

Animals↗

Neuronal and behavioral sensitivity to binaural time differences in the owl.

We demonstrated that ongoing time disparity (OTD) was a sufficient cue for the azimuthal component of receptive fields of auditory neurons in the owl (Tyto alba) midbrain and that OTDs were sufficient to mediate meaningful behavioral responses. We devised a technique which enabled us to change easily between free field and dichotic stimuli while recording from single auditory neurons in the owl mesencephalicus lateralis pars dorsalis (MLD). MLD neurons with restricted spatial receptive fields ("space-mapped neurons") showed marked sensitivity to specific ongoing time disparities. The magnitudes of these disparities were in the behaviorally significant range of tens of microseconds. The ongoing time disparities were correlated significantly with the azimuthal center of receptor fields. Space-mapped neurons were insensitive to transient disparities. MLD neurons which were not space-mapped, i.e., were omnidirectional, did not show any sensitivity to specific OTDs. We confirmed the behavioral relevance of OTD as a cue for localizing a sound in azimuth by presenting OTD differences to tame owls. Using head turning as an assay, we showed that OTD was a sufficient cue for the azimuth of a sound. The relationship between azimuth and OTD obtained from our neurophysiological experiments matched closely the relationship obtained from our behavioral experiments.

Acoustic Stimulation↗

Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling.

Neurons of the nucleus magnocellularis (nMAG) of the chick express AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) receptors displaying unusually rapid kinetics of desensitization (Raman and Trussell, 1992a). To investigate whether fast AMPA receptors are present in other auditory neurons, we compared the properties of AMPA receptors in auditory as well as nonauditory cells. These included neurons of nMAG, the nucleus angularis, the nucleus laminaris, the cochlear ganglion, the Purkinje cell layer of the cerebellum, the ventral horn of the spinal cord, and the brainstem nucleus of the glossopharyngeal nerve (ncIX). Rapid application of glutamate to voltage-clamped outside-out membrane patches indicated that AMPA receptors in the four types of auditory cells had significantly faster kinetics of desensitization than did the three types of nonauditory neurons. Channel kinetics in auditory (nMAG) and nonauditory (ncIX) cells were also compared by means of spectral analysis and the time course of current deactivation upon removal of glutamate. Both techniques revealed a burst duration for nMAG channels of 400-500 musec at room temperature, two to three times shorter than for ncIX cells. Single channels in nMAG had a burst duration of 550 musec and an open time of approximately 150 musec. Miniature excitatory postsynaptic currents of brainstem auditory neurons in slices were also brief, with decay constants of 150-250 musec at 29-32 degrees C. We demonstrated that the fast kinetics of this AMPA receptor are physiologically important, since cyclothiazide, which reduces desensitization and prolongs synaptic currents, doubled the relative refractory period of orthodromic spikes in nMAG cells in brain slices. We conclude that auditory brainstem neurons express a specialized subtype of AMPA receptors. This "fast" AMPA receptor may be useful in transmitting signals necessary for sound localization.

Animals↗

Neural delays shape selectivity to interaural intensity differences in the lateral superior olive.

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.

Animals↗

Central auditory processing in an adult with congenital absence of left temporal lobe.

A young adult subject with congenital absence of the left temporal lobe received extensive behavioral and electrophysiologic tests to identify deficits in central auditory processing. Tests included the dichotic digits, staggered spondaic words (SSW), synthetic sentence identification with ipsilateral (SSI-ICM) and contralateral (SSI-CCM) competing messages, pitch pattern, and duration pattern measures. Additional special tests included the precedence effect in sound localization, measurement of frequency difference limens for short (5 msec) and long (200 msec) duration tones, and the P300 event-related potential. The subject's performance on all measures was well within normal limits. These findings provide important new evidence that reinforces the belief of neuroscientists that the developing nervous system exhibits a remarkable degree of functional plasticity.

Adult↗

Neurobehavioral studies of the central auditory system.

The history of ablation-behavior experimentation into the central system has led to conclusions not obviously derivable from knowledge of neuroanatomy or neurophysiology alone. 1) The ventral, and not the dorsal, acoustic stria is necessary and sufficient for discriminating the physical dimensions of sound. 2) The ventral, and not the dorsal, system is also necessary and sufficient for discriminations of both the azimuth and elevation of a sound source. 3) A functional "acoustic chiasm" is centered in the superior olivary complex, resulting in the neurobehavioral "representation" of each acoustic hemifield only in the contralateral side of the central system (despite the presence of ipsilateral activity). 4) The behavioral usefulness of the ipsilateral activity present above the superior olivary complex, the role of the entire dorsal acoustic system, and the role of the descending system remain unknown. The fact that the only clear structural-behavioral correspondence yet known is that between the superior olives and sound localization seems to suggest that the more fruitful avenues of further inquiry into the roles of the central auditory system might lie in the more biologic (or Darwinian) as opposed to the physical (or Helmholtzian) dimensions of auditory processing.

Animals↗

Effects of early deafness on development of brain stem auditory neurons.

Early destruction of the otocyst (embryonic precursor of the inner ear) in chick embryos results in complex changes in developing central auditory pathways. In the cochlear nucleus angularis (NA) and nucleus magnocellularis (NM), 30% to 40% of the neurons die after otocyst removal, the survivors are shrunken, and some neurons in the NA migrate to an abnormal position in the brain stem. The characteristic forms of cochlear nucleus neurons develop normally in the absence of cochlear nerve input, however. In the nucleus laminaris (NL), development of normal dendritic size is dependent on a normal inner ear, but most of the highly specialized dendritic organization of this nucleus, which is important for low-frequency sound localization, can develop normally in the absence of cochlear influences. Otocyst removal induces formation of a permanent functional aberrant axonal projection to the ipsilateral NM from the contralateral NM. Although these aberrant axons form functional glutamatergic synapses, these show immature functional properties, suggesting that cochlear nerve inputs are necessary for normal maturation of glutamate receptors on auditory neurons. Treatment of chick embryo for a brief period in ovo with 6-cyano-7-nitroquinoxaline-2,3-dione, a quinoxalinedione antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate subtype of glutamate receptor, completely and permanently prevents the neuronal loss in the NM produced by otocyst removal. The work reviewed has 1) identified aspects of development in central auditory neurons that are perturbed by profound early sensorineural loss, 2) identified aspects of development that appear independent of cochlear influences, and 3) suggested a potential chemotherapeutic approach to prevention of central neuronal death after early damage to the cochlea.

Animals↗

Acoustic neuroma surgery: outcome analysis of patient-perceived disability.

OBJECTIVE: Numerous studies have investigated the outcome of acoustic neuroma (AN) treatment using classical medical measures. In an effort to describe the long-term lifestyle consequences of AN removal from the patient's perspective, patients filled out detailed questionnaires concerning their functional status. STUDY DESIGN: This was a retrospective survey. SETTING: This study was performed at a tertiary referral center. PATIENTS: A total of 130 late postoperative acoustic neuroma patients were surveyed a minimum of 6 months following surgery (average, 39 months). Survey response rate was 65% (130/200). MAIN OUTCOME MEASURES: The main outcome measures were the patient's perception of their hearing, balance, facial expression, and eye function in relation to its impact upon the activities of daily life. A comparison of pretreatment with long-term posttreatment functional levels. RESULTS: When asked to designate their "most significant" symptom, hearing loss was by far most prevalent (61.3%), followed by balance troubles (14.3%) and facial weakness (10.1%). The relatively low incidence of facial weakness as the patient's dominant complaint was somewhat surprising. When considering the incidence of each symptom, women were more likely to complain of facial weakness, dry eye, and headache, whereas men had a marginally higher incidence of hearing loss and imbalance. Patient age had no apparent influence upon either the distribution or severity of symptomatic complaints. Both hearing in the tumor ear and overall auditory function (e.g., the ability to understand in a restaurant) tended to worsen following surgery. One finding, which was both unanticipated and intriguing, was the improvement in sound localization ability reported by 57% of patients following surgery. Although the proportion of patients complaining of frequent tinnitus increased postoperatively, the number of patients who found the tinnitus troublesome decreased markedly. In terms of balance function, only 31% preoperatively and 15% postoperatively described themselves as free of balance difficulties. An aid to ambulation (e.g., cane, walker) was needed in five patients (4%) preoperatively, two of whom regained the ability to walk independently following tumor removal. CONCLUSIONS: These functional outcome data provide much useful information to both patient and clinician to consider when contemplating the optimal course of AN management. Although virtually all acoustic neuroma patients have some degree of persistent symptoms over the long-term, the data indicates that most of these are attributable to the tumor itself as opposed to the after effects of its surgical removal. The relatively slight differences between preoperative and late postoperative symptom profiles was a rather unanticipated finding. As the degree of disability tends to increase with larger tumor sizes, these data tend to support a policy of early intervention.

Adolescent↗

Neuron types in the rat lateral superior olive and developmental changes in the complexity of their dendritic arbors.

The lateral superior olive (LSO), a conspicuous mammalian brainstem nucleus that is involved in sound localization, has become a model system for investigating the formation of topographically organized inhibitory and excitatory connections. In experiments employing intracellular injections of Lucifer yellow or neurobiotin into lightly fixed brain slices, we have examined the soma-dendritic morphology of 483 LSO neurons of rats between postnatal day (P) 4 and P36. A detailed analysis of the shape and complexity of dendritic arbors was performed in 238 neurons in order to identify different cell classes and to determine whether age-related changes occur that may relate to a topographical refinement. Regardless of age, seven classes of LSO neurons were identified, more than had been delineated previously with the Golgi technique. Bipolar neurons and multipolar neurons comprised the two major cell types, whereas small multipolar cells, banana-like cells, bushy cells, unipolar cells, and marginal cells were found less frequently. Age-related changes were analyzed in bipolar and multipolar neurons, and several modifications of their dendritic arbors were observed that are in accordance with a refinement of topography. For example, at P4, bipolar and multipolar cells had relatively broad dendritic arbors, with an average of 140 and 138 dendritic end branches, respectively. During further development, their numbers became drastically reduced by about 80%, such that an average of less than 30 endpoints remained by P36. As the dendritic arbors became smaller specifically along the transverse axis of the LSO, they became confined to a smaller frequency area. We conclude from our results that considerable remodeling takes place in the LSO and that the selective loss of dendritic branches may be a morphological correlate for the formation of exquisite tonotopy.

Animals↗

Electrical membrane properties of trapezoid body neurons in the rat auditory brain stem are preserved in organotypic slice cultures.

The medial nucleus of the trapezoid body (MNTB) is a conspicuous structure in the mammalian auditory brain stem. It is a major component of the superior olivary complex and is involved in sound localization. Recently, organotypic slice culture preparations of the superior olivary complex were introduced to investigate the development of inhibitory and excitatory projections (Sanes and Hafidi, 1996; Lohmann et al., 1998). In the present article, we further assessed the organotypicity of our culture system (Lohmann et al., 1998) and examined electrical membrane properties of MNTB neurons expressed under culture conditions. To do so, MNTB neurons from early postnatal rats (P3-5) were studied after 3-6 days in vitro (DIV) by whole-cell patch-clamp recordings. Their mean resting potential was -59 mV, the input resistance averaged 171 Momega, and the average time constant was 3 ms. Four types of voltage-activated conductances were observed in voltage-clamp recordings. All cells expressed a tetrodotoxin (TTX)-sensitive sodium current. Two types of potassium currents could be characterized: a tetraethylammonium (TEA) -sensitive and a 4-aminopyridine (4-AP)-sensitive conductance, both of which are composed of a transient and a sustained component. Finally, an inwardly rectifying current, activated by hyperpolarizing voltage steps, was found. In current-clamp recordings, depolarizing current pulses typically elicited a single action potential. In the presence of 4-AP, however, these current pulses induced a train of action potentials. The duration of action potentials was increased by 4-AP and the afterhyperpolarization was reduced. Hyperpolarizing current injections induced a "sag" in the membrane potential, indicating the influence of an inwardly rectifying current. Our results demonstrate that MNTB neurons in slice cultures have electrical membrane properties comparable to those of their counterparts in acute slices.

4-Aminopyridine↗