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PubMed1994

Multiple-channel fractal information coding of mammalian nerve signals.

As an average of minimal 3 to maximal 30 single auditory-nerve fibers converge in the auditory pathway, the fractal geometry of their signals is transformed to a different fractal geometry such that small variations of the primary discharge patterns correspond to large variations of the combined signal. The addition of white noise does not affect the fractal signal structure. The quality of the transsynaptic information transfer depends on the relation between the number of the convergent spike trains and the individual fractal geometries of the convergent spike trains.

Animals↗
PubMed1988

Comparisons of psychophysical and neurophysiological studies of cochlear implants.

This paper compares psychophysical and neural studies of electrical stimulation of the auditory nerve with the goal of evaluating the relevance of single-unit animal models for the development of cochlear prostheses for profoundly deaf humans. Comparative psychophysical studies with implanted deaf subjects indicate that animal models, at least nonhuman primates, provide a close match to humans, though this is not always true for acoustic stimulation of normal-hearing subjects. However, the human-animal comparisons, especially those involving electrical stimuli, need further study using more carefully matched conditions. Comparisons of psychophysical and neurophysiological thresholds for electrical stimulation in animals reveal consistently higher thresholds in the neural studies. A number of factors which may account for these differences are discussed. A partial resolution of the problem could result from conducting neurophysiological and behavioral studies in the same animal. Finally, comparison of psychophysical and neurophysiological studies of temporal encoding suggest that there may be more information encoded in the auditory nerve than is used by the system, at least for nonspectral frequency discrimination. This points to a need for further analysis of the processing of this information at higher levels in the auditory pathway.

Animals↗
PubMed1985

Preyer reflex in jaundiced rats: central auditory effects.

Normal control rats (N:45) and 27 genetically hyperbilirubinemic rats from an NIH colony were tested for the Preyer reflex (Pr) threshold using pure tones. About half of all animals (N:39) were tested at 4, 6, and 8 kc/s only, while 39 were also tested at 10, 15, 20, 25, and 30 kc/s. Data were not included from 3 jaundiced rats who died during the study, which began when Ss were 3 wks old. Some jaundiced rats differed from control rats in their elevated Pr thresholds for mid-frequency tones (approximately 10 kc/s) (group mean threshold difference of 6.4 db (p less than .05). Since jaundiced rats have been shown to have extensive damage in the first brain-stem synapse, neural dysfunction can be inferred. The Pr of jaundiced rats did not differ from normals at frequencies below 10 kc/s. Normal low-frequency sensitivity in jaundiced rats likely represents a tonotopic vulnerability gradient in the central auditory pathway.

Animals↗
PubMed1984

Is the inferior colliculus an obligatory relay in the cat auditory system?

The status of the inferior colliculus of the cat as an obligatory relay in the ascending auditory pathway was examined by attempting to infiltrate totally the fibres of the brachium of the inferior colliculus on one side with horseradish peroxidase. Following a transport time of 24 h, alternate sections from thalamus to caudal brainstem were reacted with a sensitive histochemical method to reveal tracer reaction product. Results for three cats revealed that the inferior colliculus is an obligatory relay for the overwhelming majority of axons comprising the lateral lemniscus and originating in the cochlear nucleus and superior olive.

Animals↗
PubMed2006

Anatomical evidence of impaired feedforward auditory processing in schizophrenia.

BACKGROUND: Somal volumes of pyramidal cells are reduced within feedforward but not feedback circuits in areas 41 and 42 of the auditory cortex of subjects with schizophrenia. Because neuronal somal volume depends on both the number of axonal terminations onto and furnished by the neuron, we hypothesized that axon terminal densities are reduced in feedforward but not feedback auditory pathways in subjects with schizophrenia. METHODS: We used stereologic methods to quantify the density of a marker of axon terminals, synaptophysin-immunoreactive (SY-IR) puncta, in areas 41 and 42 of 15 subjects with schizophrenia and matched normal comparison subjects. The effect of long-term haloperidol exposure on density of SY-IR puncta was similarly evaluated in nonhuman primates. RESULTS: Synaptophysin-immunoreactive puncta density was 13.6% lower in deep layer 3 of area 41 in the schizophrenia subjects but was not changed in layer 1 of area 41 or in deep layer 3 of area 42. Density of SY-IR puncta did not differ between haloperidol-exposed and control monkeys. CONCLUSIONS: Reduction of SY-IR puncta density is selective for feedforward circuits within primary auditory cortex of subjects with schizophrenia. This deficit may contribute to impairments in auditory sensory processing in this disorder.

Adult↗
PubMed1997

Regulation of D-aspartate release and uptake in adult brain stem auditory nuclei after unilateral middle ear ossicle removal and cochlear ablation.

In young adult guinea pigs, the effects of unilateral ossicle removal and cochlear ablation were determined on transmitter release from glutamatergic presynaptic endings and glutamate inactivation via uptake. (i) D-[3H]Aspartate release and uptake were measured in subdivisions of the cochlear nucleus (CN) and in nuclei of the superior olive (SOC) and auditory midbrain (MB) up to 145 days after placing the lesions. Activities were compared to those from age-matched unlesioned controls. Fiber degeneration was visualized histologically. (ii) In the ipsilateral CN, changes in release and uptake were governed by the type of lesion. Ossicle removal produced sparse pruning of fibers only after 112 days and decreased release and uptake at 145 days, consistent with regulatory weakening of excitatory glutamatergic transmission. Cochlear ablation deafferented the CN, producing deficient release and uptake at 2 days and abundant fiber degeneration at 7 days. Subsequently, the residual release and uptake increased in magnitude, consistent with strengthening of excitatory glutamatergic transmission. (iii) In the contralateral CN, after either lesion, changes in release and uptake usually matched those in the ipsilateral CN. Thus, the auditory pathway associated with the lesioned ear probably provided cues for the regulation of synaptic strength in the contralateral CN. (iv) Both lesions increased release in the SOC and MB, and uptake in the SOC, consistent with strengthening of excitatory glutamatergic transmission. Sparse fiber degeneration, suggesting axonal pruning, appeared in the SOC and MB after cochlear ablation. (v) The strengthening of excitatory glutamatergic transmission may facilitate and maintain symptoms such as loudness recruitment and tinnitus which often accompany hearing loss.

Animals↗
PubMed1993

Effect of unilateral partial cochlear lesions in adult cats on the representation of lesioned and unlesioned cochleas in primary auditory cortex.

We examined the effect of unilateral restricted cochlear lesions in adult cats on the topographic representations ("maps") of the lesioned and unlesioned cochleas in the primary auditory cortex (AI) contralateral to the lesioned cochlea. Frequency (tonotopic) maps were derived by conventional multineuron mapping procedures in anesthetized animals. In confirmation of a study in adult guinea pigs (Robertson and Irvine [1989] J. Comp. Neurol. 282:456-471), we found that 2-11 months after the unilateral cochlear lesion the map of the lesioned cochlea in the contralateral AI was altered so that the AI region in which frequencies with lesion-induced elevations in cochlear neural sensitivity would have been represented was occupied by an enlarged representation of lesion-edge frequencies (i.e., frequencies adjacent to those with elevated cochlear neural sensitivity). Along the tonotopic axis of AI the total representation of lesion-edge frequencies could extend up to approximately 2.6 mm rostal to the area of normal representation of these frequencies. There was no topographic order within this enlarged representation. Examination of threshold sensitivity at the characteristic frequency (CF, frequency to which the neurons were most sensitive) in the reorganized regions of the map of the lesioned cochlea established that the changes in the map reflected a plastic reorganization rather than simply reflecting the residue of prelesion input. In contrast to the change in the map of the lesioned contralateral cochlea, the map of the unlesioned ipsilateral cochlea did not differ from those in normal animals. Thus, in contrast to the normal very good congruency between ipsilateral and contralateral AI maps, in the lesioned animals ipsilateral and contralateral maps differed in the region of AI in which there had been a reorganization of the map of the lesioned cochlea. Outside the region of contralateral map reorganization, ipsilateral and contralateral AI maps remained congruent within normal limits. The difference between the two maps in the region of contralateral map reorganization suggested, in light of the physiology of binaural interactions in the auditory pathway, that the cortical reorganization reflected subcortical changes. Finally, response properties of neuronal clusters within the reorganized map of the lesioned cochlea were compared to normative data with respect to threshold sensitivity at CF, the size of frequency "response areas," and response latencies. In the majority of cases, CF thresholds were similar to normative data. The frequency "response areas" were slightly less sharply tuned than normal, but not significantly. Response latencies were significantly shorter than normal in three animals and significantly longer in one animal.

Animals↗
PubMed2003

Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2.

NB-2, a member of the contactin subgroup in the immunoglobulin superfamily, is expressed specifically in the postnatal nervous system, reaching a maximum level at 3 weeks postnatal. NB-2 displays neurite outgrowth-promoting activity in vitro. To assess its function in the nervous system, we generated mutant mice in which a part of the NB-2 gene was ablated and replaced with the tau-LacZ gene. The general appearance of NB-2-deficient mice and their gross anatomical features were normal. The LacZ expression patterns in heterozygous mice revealed that NB-2 is preferentially expressed in the central auditory pathways. In the audiogenic seizure test, NB-2-deficient mice exhibited a lower incidence of wild running, but a higher mortality rate than the wild-type littermates. c-Fos immunohistochemistry demonstrated that neural excitability induced by the audiogenic seizure test in the NB-2-deficient mice was prominently attenuated in both the dorsal and external cortices of the inferior colliculus, where enhanced neural excitability was observed in the wild-type mice. In response to pure-tone stimulation after priming, NB-2-deficient mice exhibited a diffuse and low level of c-Fos expression in the central nucleus of the inferior colliculus, which was distinctly different from the band-like c-Fos expression corresponding to the tonotopic map in the wild-type littermates. Taken together, these results suggest that a lack of NB-2 causes impairment of the neuronal activity in the auditory system.

Acoustic Stimulation↗
PubMed1997

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↗
PubMed1981

Pathology of the auditory system in autosomal trisomies with morphometric and quantitative study of the ventral cochlear nucleus.

Anomalies of the peripheral auditory system have been reported in major autosomal trisomies. In order to investigate the central auditory pathway, a quantitative and morphometric study of the ventral cochlear nucleus was performed in 2 cases of trisomy 13, 2 cases of trisomy 18 and 1 case of trisomy 21. Data were obtained using a Cambridge Imanco Quantimet 720 Image Analyzing System according to the methods already described. For statistical evaluation, trisomy 13 and 18 cases were considered as group 1-trisomies and compared to full-term controls. Each trisomy was then compared separately to both premature and full term control groups. Trisomy 21 was investigated separately. Quantitative data in trisomy 18 suggest a slight maturational retardation of the ventral cochlear nucleus with respect to gestational age. No significant abnormalities were detected in trisomy 13, aside from those determined by the age difference, when compared to premature controls. The estimated total number of neurons in both trisomies did not differ statistically from that of the control groups. Other brain stem auditory nuclei did not show relevant pathology. Golgi impregnation of the temporal cortex revealed immature neuronal development, especially in trisomy 13. Trisomy 21 showed a greatly reduced number of neurons in the ventral cochlear nucleus, a small nuclear volume, low cell packing density and an abnormally large mean neuronal diameter. The findings of this investigation are discussed and tentatively correlated to the hearing defects reported in these trisomies.

Auditory Pathways↗
PubMed1994

Distribution of calcium-binding protein calbindin-D28k in the auditory system of adult and developing rats.

Calbindin-D28k (CaBP) is a calcium-binding protein, which appears to be involved in the buffering of free intracellular calcium and may thereby contribute to calcium homeostasis. This study attempted to determine the distribution pattern of CaBP immunoreactivity in the central auditory system of adult rats and during development, when calcium ions play key roles in several aspects of nerve cell function. It was found that most steps during CaBP development occur postnatally in the central auditory system. With the exception of the lateral superior olive, the ventral and the intermediate nuclei of the lateral lemniscus, and the auditory cortex, which already express CaBP prenatally, CaBP immunoreactivity is not present before postnatal day 2 (P2). Development proceeds until about P24, when the pattern characteristic of adult animals can be seen. There was no detectable sequence in CaBP development from lower to higher stations in the auditory pathway, i.e., the different nuclei appear to express CaBP independently of each other, indicating that intrinsic, rather than peripheral, maturation processes may predominantly influence CaBP expression. Neurons in four brainstem nuclei (the lateral superior olive, the ventral and intermediate nuclei of the lateral lemniscus, and the central nucleus of the inferior colliculus) express CaBP only transiently. In these nuclei, CaBP immunoreactivity peaks between P6 and P18, which coincides with the period of synapse stabilization. Therefore, CaBP may play a specific role during neuronal development, by buffering the concentration of intracellular free Ca2+, which may be necessary for modification of synaptic efficiency.

Animals↗
PubMed2006

A GABAergic component in the commissure of the inferior colliculus in rat.

The commissure of the inferior colliculus is significant as the final point of interconnection between homologous structures on the two sides of the auditory pathway at the subcortical level. The presence of excitatory fibres is well established in this tract, but the existence of an inhibitory component is controversial. Using rats, we injected biotinylated dextran amine into the inferior colliculus on one side to retrogradely label cells projecting through the commissure from the contralateral inferior colliculus. Immunocytochemistry for gamma-amino-n-butyric acid in neighbouring semithin sections revealed that 20% of biotinylated dextran amine cell profiles were also labelled for gamma-amino-n-butyric acid. We conclude that monosynaptic inhibitory connections contribute to the inhibition observed in the contralateral inferior colliculus in functional studies of the commissural projection.

Animals↗
PubMed1975

Degenerative alterations in the ventral cochlear nucleus of the guinea pig after impulse noise exposure. A preliminary light and electron microscopic study.

Guinea pigs were exposed to the noise of 40 shots of an alarm pistol held at a distance of about 60 cm. The ventral cochlear nuclei were studied in phase contrast and electron microscopy after both survival periods and longer periods of up to 55 days survival. Marked degeneration of primary cochlear nerve endings and of synapting secondary neurons of the posterior caudal part of the ventral cochlear nucleus (AVCN) and the octupus cell area (OCA) of the posterior ventral cochlear nucleus (PVCN) was found most distinctly after 5-55 days. As criteria of degeneration of the second neuron of the afferent auditory pathway we used: 1. The loss of the synapting nerve endings, mainly 'shrinking". 2. The formation of huge mitochondria in the second order neurons and their dendrites. 3. The phagocytosis by glial cells of nerve endings, of the second order neurons and of their dendrites. After 5 days survival time no distinct changes were found in the granular cell area of PVCN, where as all stages of degeneration could be found in OCA at this time. In the discussion of these findings it is concluded that additional studies of the morphology of the cochlear nuclei seem necessary, as these may lead to a better understanding of the pathology of hearing following heavy noise exposure.

Animals↗
PubMed2002

Vesicle pools and short-term synaptic depression: lessons from a large synapse.

Depletion of a pool of readily releasable vesicles during repetitive presynaptic activity is a candidate mechanism for the induction of short-term synaptic depression. The large, calyx-type synaptic terminals in the brainstem auditory pathway, and especially the calyx of Held, offer unique possibilities for studying the cellular mechanisms leading to synaptic depression. Recent work at these synapses using presynaptic whole-cell patch-clamp recordings has revealed a large pool of readily releasable vesicles. During prolonged presynaptic depolarization, vesicles are released in kinetically distinct phases, indicating heterogeneity of release probability between vesicles. Heterogeneity might endow synapses with a rapid phase of depression at the onset of activity, followed by sustained and surprisingly large synaptic strength during the steady-state phase of depression. By influencing the synaptic output during repetitive activity, vesicle pool dynamics are expected to modulate information processing in neuronal networks of the CNS.

Action Potentials↗
PubMed1998

Ultrastructure of neurons and large synaptic terminals in the lateral nucleus of the trapezoid body of the cat.

Neurons of the lateral nucleus of the trapezoid body (LNTB), the most prominent periolivary nucleus of the cat superior olivary complex, form an important component of the descending auditory pathways and also innervate the medial superior olive. Cells forming the posteroventral subnucleus (pvLNTB), when investigated by light microscopy, exhibit morphological similarities with globular bushy cells of the cochlear nucleus and principal cells of the medial nucleus of the trapezoid body. These latter two cell types are integral components of brainstem circuitry mediating the early stages of sound localization. In this report, ultrastructural features of LNTB neurons are described. pvLNTB cell bodies are characterized by a round to oval shape, smooth nuclear membrane, and the relative paucity of stacks of rough endoplasmic reticulum. In addition, pvLNTB cell bodies and proximal dendrites are contacted by large synaptic terminals which contain round synaptic vesicles and form multiple asymmetric synaptic junctions. These ultrastructural characteristics are similar to those previously described for globular and principal cells and distinguish pvLNTB cells from cells of the main subnucleus. Large terminals contacting pvLNTB cells contain a specialized organelle assembly, including an adherens plaque associated by filamentous strands with a mitochondrion. We name this organelle assembly the mitochondria-associated adherens complex (MAC) and note its proximity to synaptic junctions. Because high activity rates are characteristic of large terminals in the lower auditory system, the MAC may play a specialized role in membrane stabilization at synapses which generate high rates of vesicle membrane turnover.

Animals↗
PubMed2005

Deafness-related decreases in glycine-immunoreactive labeling in the rat cochlear nucleus.

There is increasing evidence of activity-related plasticity in auditory pathways. The present study examined the effects of decreased activity on immunolocalization of the inhibitory neurotransmitter glycine in the cochlear nucleus of the rat after bilateral cochlear ablation. Specifically, glycine-immunoreactive puncta adjacent to somatic profiles were compared in normal hearing animals and animals deafened for 14 days. The number of glycine-immunoreactive puncta surrounding somatic profiles of spherical and globular bushy cells, glycine-immunoreactive type I stellate multipolar cells, radiate neurons (type II stellate multipolar cells), and fusiform cells decreased significantly. In addition, the number of glycine immunopositive tuberculoventral (vertical or corn) cells in the deep layer of the dorsal cochlear nucleus also decreased significantly. These results suggest that decreased inhibition reported in cochlear nucleus after deafness may be due to decreases in glycine.

Animals↗
PubMedDate not supplied

Effect of click rate on the latency of auditory brain stem responses in humans.

Auditory brain stem responses are the far-field reflections of electrical activity originating in the auditory pathway in its course from the cochlea to cortex that can be recorded from scalp electrodes using computer averaging techniques. There are seven components in the initial 10 msec following a click signal which have been shown to have an orderly change in latency as a function of signal intensity. The results of this study show that click repetition rate can also significantly affect the response latency measure. Responses were measured in six normal hearing subjects at click rates of 10, 30, 50 and 100/sec and af four intensity levels (30, 40, 50, and 60 dB sensation level). The mean latency shift of component V was approximately 0.5 msec when the responses at 10 and 100/sec were compared. This is equivalent to a 15-20 dB decrease in signal intensity at the 10/sec click rate. An analysis of the time of occurrence of this shift using brief click trains at 100/sec showed the shift in latency to be complete by the fifth click. The latency shift was similar at the four signal levels tested. The latency shift was similar at the four signal levels tested. The latency shift of component V appeared to be a monaural and therefore a potentially peripheral process. The results are interpreted as an objective measure of adaptation in the human auditory system with implications for the measurement in disorders of hearing.

Acoustic Stimulation↗
PubMed1996

Whole-cell patch-clamp recording reveals subthreshold sound-evoked postsynaptic currents in the inferior colliculus of awake bats.

The inferior colliculus receives excitatory and inhibitory input from parallel auditory pathways that differ in discharge patterns, latencies, and binaural properties. Processing in the inferior colliculus may depend on the temporal sequence in which excitatory and inhibitory synaptic inputs are activated and on the resulting balance between excitation and inhibition. To explore this issue at the cellular level, we used the novel approach of whole-cell patch-clamp recording in the midbrain of awake bats (Eptesicus fuscus) to record EPSCs or IPSCs. Sound-evoked EPSCs were recorded in most neurons. These EPSCs were frequently preceded by an IPSC, followed by an IPSC, or both. These findings help explain the large latency range and transient responses that characterize inferior colliculus neurons. The EPSC was sometimes followed by long-lasting oscillatory currents, suggesting that a single brief sound sets up a pattern of altered excitability that persists far beyond the duration of the initial sound. In three binaural neurons, ipsilateral sound evoked a large IPSC that partially or totally canceled the EPSC evoked by contralateral sound. In one binaural neuron with ipsilaterally evoked IPSCs, contralaterally evoked IPSCs occurred in response to frequencies above and below the neuron's best frequency. Thus, both monaural and binaural interactions can occur at single inferior colliculus neurons. These results show that whole-cell patch-clamp recording offers a powerful means of understanding how subthreshold processes determine the responses of auditory neurons.

Acoustic Stimulation↗