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Central trajectories of type II spiral ganglion neurons.

Previous attempts to trace the central pathways of the thin axons from type II spiral ganglion neurons have been hampered by technical difficulties such as fading of the reaction product as distance increases from the injection site (Ryugo et al.: Soc. Neurosci. Abstr. 12:779, '86; Brown: J. Comp. Neurol. 260:591-604, '87). By using small rodents (gerbils and mice), which have short auditory nerves, we have succeeded in filling the entire central axon and terminals of type II neurons after peripheral injections of horseradish peroxidase. The general course of the type II fibers within the auditory nerve and cochlear nucleus is similar to that of type I fibers except that terminals from type II neurons are often found in regions of the cochlear nucleus that have high densities of granule cells.

Animals↗

Cytoarchitecture of auditory system in lower brainstem of the mustache bat, Pteronotus parnellii.

To begin an investigation of the auditory pathways in the brainstem of the mustache bat, we examined the cytoarchitecture of the cochlear nuclei, superior olivary complex, nuclei of the lateral lemniscus, and inferior colliculus. Although all of these auditory centers are hypertrophied in this echolocating bat, only some areas have unusual cytoarchitectural features: 1) In the anterior part of the anteroventral cochlear nucleus we do not find the large spherical cells seen in other mammals; instead, very small spherical cells are found in this area. 2) In the posterior part of the anteroventral cochlear nucleus there is a region containing a homogeneous population of very large multipolar cells. 3) The medial superior olive is unusually large for an animal with a small head. 4) The most striking observations are seen in the lateral lemniscus. The ventral nucleus of the lateral lemniscus has a distinct columnar organization. The intermediate area of the lateral lemniscus contains a large and very distinct nucleus. Each of these cytoarchitectural features distinguishes the auditory system of this bat from that of other mammals. The results raise questions about whether or not there are unique subdivisions in the auditory pathways of echolocating bats. The results also identify these unusual nuclei as candidates to play a role in the special auditory functions related to echolocation.

Animals↗

Somatostatin and substance P-like immunoreactivity in the auditory brainstem of the adult rat.

The superior olivary complex (SOC) of the adult rat brainstem was studied in detail with regard to its innervation by neural elements showing immunoreactivity for two neuroactive peptides, somatostatin and substance P. Nerve fibres and varicosities showing positive immuno-reactivity for both peptides were particularly dense immediately dorsal and lateral to the lateral superior olivary nucleus (LSO) and dorsal to the superior paraolivary nucleus (SPN). Penetration of this curtain-like innervation into the SPN was limited, and the LSO showed only a very minor innervation by somatostatin-positive structures in its most medial (high frequency) lobe. Dense fibre labelling and varicosities were also apparent for both peptides immediately medial to the ventral and dorsal nuclei of the lateral lemniscus, and in the external cortex and dorsomedial zones of the inferior colliculus (IC). Labelled fibres and endings were also seen in the granule cell regions of anteroventral cochlear nucleus (AVCN) and the most dorsomedial parts of the dorsal cochlear nucleus (DCN). The majority of cells in the medial nucleus of the trapezoid body (MNTB) showed a prominent innervation by nerve terminals that stained positive for somatostatin only whereas the medial superior olivary nucleus (MSO) was devoid of label for both peptides. The ventral nucleus of the trapezoid body (VNTB) showed sparse but significant innervation by both somatostatin and substance P-positive structures. Hence the VNTB was the only defined nucleus of the SOC to show a significant substance P-positive innervation. Neuronal somata immuno-reactive for somatostatin were found in anteroventral and posteroventral cochlear nuclei (AVCN and PVCN) and the A5 and A7 cell groups adjacent to the LSO and the VNLL and DNLL and in all subdivisions of the inferior colliculus (IC). Somata showing only faint immunoreactivity for substance P were found in the VNLL, AVCN and PVCN. These results suggest a potential role for both peptides in auditory signal processing in the adult rat brain.

Age Factors↗

Network analysis of functional auditory pathways mapped with fluorodeoxyglucose: associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.

The purpose of this study was to examine how opposite learned associative properties of the same auditory stimulus are represented by the pattern of network interactions between auditory system structures. [14C(U)]2-fluoro-2-deoxyglucose (FDG) autoradiography was used to compare mean auditory system activity and interregional correlations resulting from the presentation of a tone trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained with reinforced trials of the conditioned excitor (A+) intermixed with non-reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor group, the tone was the excitor (A+), while for the Conditioned Inhibitor group the tone was the inhibitor (X-). After conditioning, both groups were injected with FDG and presented with the same tone. Structural equation models, constructed from the anatomical connections between auditory regions and their interregional correlations in FDG uptake, were used to calculate path coefficients representing the network interactions. The opposite associative significance of the tone was reflected as functional changes in the interactions between parallel auditory pathways. Direct covariance effects through lemniscal pathways from the ventral cochlear nucleus were similar in absolute magnitude but differed in sign between the Excitor and Inhibitor network models. Extra-auditory influences on the dorsal cochlear nucleus were greater for the tone-inhibitor, reflecting possible interactions of this nucleus with extra-auditory regions. The different associative effects of the tone suggest that central auditory pathways can code not only the physical qualities, but also the associative significance of auditory stimuli. These findings demonstrate that neural network interactions differentiate the associative effects of tones in the brain. It is proposed that associative learning is a distributed property of neural networks and that such a property can be understood by considering the interactions between component parts of the network.

Acoustic Stimulation↗

Glutamatergic calcium responses in the developing lateral superior olive: receptor types and their specific activation by synaptic activity patterns.

The lateral superior olive (LSO) is a binaural auditory brain stem nucleus that plays a central role in sound localization. Survival and maturation of developing LSO neurons critically depend on intracellular calcium signaling. Here we investigated the mechanisms by which glutamatergic afferents from the cochlear nucleus increase intracellular calcium concentration in LSO neurons. Using fura-2 calcium imaging in slices prepared from neonatal mice, we found that cochlear nucleus afferents can activate all major classes of ionotropic and metabotropic glutamate receptors, each of which contributes to an increase in intracellular calcium. The specific activation of different glutamate receptor classes was dependent on response amplitudes and afferent stimulus patterns. Low-amplitude responses elicited by single stimuli were entirely mediated by calcium-impermeable AMPA/kainate receptors that activated voltage-gated calcium channels. Larger-amplitude responses elicited by either single stimuli or stimulus trains resulted in additional calcium influx through N-methyl-d-aspartate receptors. Finally, high-frequency stimulation also recruited group I and group II metabotropic glutamate receptors, both of which mobilized intracellular calcium. This calcium release in turn activated a strong influx of extracellular calcium through a membrane calcium channel that is distinct from voltage-gated calcium channels. Together, these results indicate that before hearing onset, distinct patterns of afferent activity generate qualitatively distinct types of calcium responses, which likely serve in guiding different aspects of LSO development.

Afferent Pathways↗

Dual electrode stimulation using the nucleus CI24RE cochlear implant: electrode impedance and pitch ranking studies.

OBJECTIVE: The first aim of the study was to determine the reduction in electrode impedances using dual electrode stimulation compared with single electrode stimulation in the new Nucleus CI24RE receiver-stimulator. The CI24RE is connected to the Nucleus 22-electrode intracochlear array. Dual electrode stimulation is produced by electrically coupling two adjacent single electrodes. The second aim was to determine whether dual electrode stimulation produced pitch percepts that were intermediate to the pitch of the two adjacent single electrodes. DESIGN: Eight postlingually hearing-impaired adults with severe to profound loss, implanted with the CI24RE, participated in the study. Electrode impedances were measured by using the standard telemetry function of the system. A pitch ranking task was used to measure pitch for dual and single electrodes. Seven sets of three electrodes along the electrode array were tested. Each set of electrodes consisted of a dual electrode and the two adjacent single electrodes. Pitch ranking was measured using a two-alternative forced choice procedure, with the three electrodes in each set paired with each other as AB and BA pairs. The subject indicated which of the two stimuli had the higher pitch. Random variation in current level was used to remove any loudness cues. RESULTS: The average electrode impedance was 38.6% lower for dual electrodes compared with single electrodes. Three subjects were able to successfully rank the three electrodes in each set in the expected tonotopic order for all seven sets of electrodes along the array. Three other subjects were able to rank sets of electrodes in the tonotopic order for most of the tested positions on the array. The remaining two subjects gave more variable pitch ranking across positions along the array, although successful tonotopic ranking was demonstrated for several sets of electrodes. CONCLUSIONS: Dual electrode stimulation with the CI24RE receiver-stimulator produced systematically lower electrode impedances and was capable of producing pitch percepts that were intermediate to those produced by the corresponding adjacent single electrodes. This makes available up to 43 channels of stimulation from 22 single electrodes.

Adult↗

[Monaural phasic sensitivity of auditory system neurons in the cat].

During monaural stimulation, studies have been made of impulse reactions in neurons from the cochlear nucleus and inferior colluculus to changes in the phase value (psi) of one of the harmonics in two-tone signals. It was shown that about 70% of the neurons from the cochleaur nucleus with a tonic discharge pattern may sharply change their activity (from maximum one up to a complete inhibition) due to changes in psi value. Unlike the cochlear nucleus units, neurons from the inferior colliculus change their tonic or burst-like activity rather seldomly and to a slight extent. At the same time, their phasic on- and especially off-responses exhibit high sensitivity to changes in psi value.

Acoustic Stimulation↗

[The auditory pathway in guinea pigs. A [14C]2-deoxyglucose study (author's transl)].

The auditory pathway of guinea pigs was labeled with [14C]-deoxyglucose after mon- or binaural stimulation with farfield white noise in a sound-proof chamber. In the autoradiographs, all auditory nuclei were labeled. The highest metabolic effects were seen in the dorsal cochlear nucleus, the lateral superior olivary nucleus, and in the inferior colliculus. No selective labeling was observed in the auditory cortex. Monaural stimulation depressed the metabolic activity contralaterally in the ventral cochlear nucleus and ipsilaterally in the medial nucleus of the trapezoid body, the dorsomedial periolivary nucleus, and in the inferior colliculus.

Acoustic Stimulation↗

Time and intensity cues are processed independently in the auditory system of the owl.

Space-specific neurons, found in the barn owl's inferior colliculus, respond selectively to a narrow range of interaural time and intensity differences. We show that injecting a local anesthetic into one cochlear nucleus, nucleus magnocellularis, alters the space-specific cell's selectivity for interaural time difference, leaving its selectivity for interaural intensity difference intact. Anesthetizing the other cochlear nucleus, nucleus angularis, has the converse effects. We show also that the space-specific neuron's selectivity for one interaural cue is the same for all effective values of the other cue. We conclude that time and intensity cues are processed in separate neural channels of the barn owl's auditory system and that the two cues operate independently.

Animals↗

Interaural phase and level difference sensitivity in low-frequency neurons in the lateral superior olive.

The lateral superior olive (LSO) is believed to encode differences in sound level at the two ears, a cue for azimuthal sound location. Most high-frequency-sensitive LSO neurons are binaural, receiving inputs from both ears. An inhibitory input from the contralateral ear, via the medial nucleus of the trapezoid body (MNTB), and excitatory input from the ipsilateral ear enable level differences to be encoded. However, the classical descriptions of low-frequency-sensitive neurons report primarily monaural cells with no contralateral inhibition. Anatomical and physiological evidence, however, shows that low-frequency LSO neurons receive low-frequency inhibitory input from ipsilateral MNTB, which in turn receives excitatory input from the contralateral cochlear nucleus and low-frequency excitatory input from the ipsilateral cochlear nucleus. Therefore, these neurons would be expected to be binaural with contralateral inhibition. Here, we re-examined binaural interaction in low-frequency (less than approximately 3 kHz) LSO neurons and phase locking in the MNTB. Phase locking to low-frequency tones in MNTB and ipsilaterally driven LSO neurons with frequency sensitivities <1.2 kHz was enhanced relative to the auditory nerve. Moreover, most low-frequency LSO neurons exhibited contralateral inhibition: ipsilaterally driven responses were suppressed by raising the level of the contralateral stimulus; most neurons were sensitive to interaural time delays in pure tone and noise stimuli such that inhibition was nearly maximal when the stimuli were presented to the ears in-phase. The data demonstrate that low-frequency LSO neurons of cat are not monaural and can exhibit contralateral inhibition like their high-frequency counterparts.

Acoustic Stimulation↗

Regional cerebral palmitate incorporation after unilateral auditory deprivation in immature and adult Fischer-344 rats.

Regional cerebral incorporation of intravenously injected [U-14C]palmitate was measured from 1 day to 13 weeks after left cochlear destruction in 11-day- and 3 month-old, awake Fischer-344 rats. In 11-day-old animals, statistically significant left-right differences in incorporation were absent 1 day after cochlear destruction and were found only in parts of the cochlear nucleus and inferior colliculus after 1 week. After 6 to 13 weeks, consistent with functional neuroanatomy of central auditory regions, incorporation was reduced by 6 to 9% in the left cochlear nucleus and left lateral superior olivary nucleus, compared with corresponding right-side regions. The right medial superior olivary nucleus, medial nucleus of the trapezoid body, lateral lemniscus nucleus, inferior colliculus, medial geniculate body, and auditory cortex had 5 to 9% less incorporation than did corresponding left-side regions. Fewer significant differences after chronic auditory deprivation occurred in 3-month-old rats than in 11-day-old rats following cochlear destruction. Reduced incorporation corresponded to reported changes in cell morphology, which also were greater in immature than mature rats following auditory deprivation. The results suggest that the palmitate method can be used to identify long-term regional changes in the turnover of brain lipids after sensory deprivation.

Animals↗

The role of intrinsic neuronal properties in the encoding of auditory information in the cochlear nuclei.

It is now possible to relate the intrinsic electrical properties of particular cells in the cochlear nuclei of mammals with their biological function. In the layered dorsal cochlear nucleus, information concerning the location of a sound source seems to be contained in the spatial pattern of activation of a population of neurons. In the unlayered, ventral cochlear nucleus, however, neurons carry information in their temporal firing patterns. The voltage-sensitive conductances that make responses to synaptic current brief enable bushy cells to convey signals from the auditory nerve to the superior olivary complex with a temporal precision of at least 120 microseconds.

Animals↗

Distribution of GABAergic neurons and terminals in the auditory system of the barn owl.

Antisera to GAD (glutamic acid decarboxylase) and GABA were used to determine the distribution of GABAergic cells and terminals in the brainstem and midbrain auditory nuclei of the barn owl. The owl processes time and intensity components of the auditory signal in separate pathways, and each pathway has a distinctive pattern of GAD- and GABA-like immunoreactivity. In the time pathway, all the cells of the cochlear nucleus magnocellularis and nucleus laminaris receive perisomatic GABAergic terminals, and small numbers of GABAergic neurons surround both nuclei. The ventral nucleus of the lateral lemniscus (anterior division) contains both immunoreactive terminals and some GABAergic neurons. In the intensity pathway, dense immunoreactive terminals are distributed throughout the cochlear nucleus angularis, which also contains a small number of GABAergic neurons. The superior olive contains two GABAergic cell types and immunoreactive terminals distributed throughout the neuropil. All the neurons of the nucleus of the lateral lemniscus (ventral part) appear to be GABAergic, and this nucleus also contains a moderate number of immunoreactive terminals. Immunoreactive terminals are distributed throughout the neuropil of the ventral nucleus of the lateral lemniscus (posterior division), whereas multipolar and small fusiform GABAergic neurons predominate in the dorsal regions of the nucleus. The time and intensity pathways combine in the inferior colliculus. The central nucleus of the inferior colliculus contains a larger number of fusiform and stellate GABAergic neurons and a dense plexus of immunoreactive terminals, whereas the external nucleus contains slightly fewer immunoreactive cells and terminals. The superficial nucleus contains dense, fine immunoreactive terminals and a small number of GABAergic neurons.

Animals↗

Localization of GABA immunoreactivity in the auditory brainstem of guinea pigs.

Using an antibody against GABA, neurons within the guinea pig hindbrain, midbrain and forebrain auditory nuclei were identified which demonstrate GABA-like immunoreactivity. GABA-positive cells were localized in the cochlear nucleus, superior olivary complex, lateral lemniscus, inferior colliculus, and medial geniculate body. GABA-positive terminals could be seen surrounding globular and spherical cells in ventral cochlear nucleus and principal cells in medial nucleus of the trapezoid body. In addition, numerous positive, punctate terminals appeared throughout the hindbrain auditory nuclei and, although fewer in number, in midbrain and forebrain auditory nuclei.

Animals↗

Excitant amino acids and audiogenic seizures in the genetically epilepsy-prone rat. I. Afferent seizure initiation pathway.

The afferent pathway involved in initiation of audiogenic seizures in the genetically epilepsy-prone rat was investigated by bilateral microinfusion of the excitant amino acid antagonist 2-amino-7-phosphonoheptanoate into the major brain stem and subcortical nuclei of the auditory system. This antagonist has been shown to possess anticonvulsant properties in other seizure models, and an excitant amino acid has been implicated as a putative neurotransmitter in several of these nuclei. Seizure severity was significantly reduced following infusion of this agent into the cochlear nucleus, superior olivary complex, inferior colliculus, and medial geniculate body. Many of these animals exhibited a complete blockade of seizures. The smallest effective dose in the cochlear nucleus and the medial geniculate body was 5 nmol per side. The smallest effective dose in the olive was 1 nmol, and in the inferior colliculus 0.1 nmol per side was protective. The onset of anticonvulsant effectiveness was earliest in the inferior colliculus. These findings showed that the inferior colliculus was the most sensitive auditory center to the anticonvulsant action of 2-amino-7-phosphonoheptanoate and that imbalance between inhibitory and excitatory transmission within this brain structure may be crucial in the initiation of audiogenic seizures in the genetically epilepsy-prone rat.

2-Amino-5-phosphonovalerate↗

Contribution from crossed and uncrossed brainstem structures to the brainstem auditory evoked potentials: a study in humans.

The neural generators of the brainstem auditory evoked potentials (BAEPs) in humans are not completely known. Attempts to identify the anatomical location of the neural generators of the human BAEP based on the results of studies in animals commonly used in auditory experimentation have been difficult because of the considerable anatomical differences between the ascending auditory pathways in humans and animals. The authors of this study compared recordings obtained from different locations on the lateral side of the brainstem in six patients undergoing microvascular decompression surgery for a cranial nerve disorder affecting the fifth cranial nerve (i.e., trigeminal neuralgia). Ipsilateral click stimulation evoked prominent responses from the caudal aspect of the pons up to the junction between the pons and the midbrain, but all components of the responses with latencies shorter than 8 msec had smaller amplitudes when recorded at more rostral locations. Components with latencies in the range of peak V elicited by contralateral click stimulation had their largest amplitudes when recorded from the lateral brainstem at the level of the fourth cranial nerve (thus, close to the inferior colliculus). Earlier components of the contralateral responses (latencies in the range of the latency of peak III) had their largest amplitudes when recorded from the caudal lateral brainstem. The results of this study indicate that the part of the uncrossed auditory pathway that is located rostral to the cochlear nucleus contributes little to the farfield potentials (i.e., BAEP), and it is doubtful whether the contralateral response that can be recorded at the level of the cochlear nucleus contributes noticeably to the BAEP.

Acoustic Stimulation↗

Effect of profound hearing loss on a central auditory nucleus.

The present study was designed to investigate the type and extent of degeneration occurring in the human central auditory system subsequent to profound hearing loss. The authors have examined the size of one population of neurons in the ventral cochlear nucleus in seven subjects with profound hearing loss (audiometric responses poorer than 90-100 dB HL). Six normal subjects, ages 35-78, were used as controls. Cell size in the hearing-impaired subjects ranged from normal to reduced by more than 50 percent. Two factors appear to contribute to the variability in cell size reduction. The correlation coefficient (Spearman rs) of cell size with duration of profound deafness was -0.48, indicating a moderate tendency for neurons to become smaller with longer periods of deafness. The correlation coefficient of cell size with number of surviving cochlear ganglion cells was 0.73, indicating a stronger tendency for neurons to be larger with greater eighth nerve innervation of the cochlear nucleus. Two cases of Scheibe degeneration showed the most severe degenerative change in the central auditory system.

Adult↗

[A longitudinal study of electrode impedance in nucleus 24M cochlear implant users].

OBJECTIVE: The primary goal of this study was to examine changes that may occur in electrode impedance over time in cochlear implant users. Secondary goal was to determine the timetable of mapping for patients who were cooperative quite well in psychophysical test. METHOD: Sixteen patients implanted with Nucleus CI24M participated in this study. The impedance of electrode was measured intra-operatively, at initial stimulation, and at each mapping visits. Statistical analysis was conducted to assess how the changes occurring over time. RESULT: There was a significant increase in electrode impedance from the intra-operative test to initial stimulation, and a significant decrease in impedance from initial stimulation to the following visit. The impedance values remained stable for approximately 2-4 months after initial stimulation. CONCLUSION: The results suggest that electrode-tissue interface gradually tend to remain stable. If a patient cooperates quite well in psychophysics test, the psychophysical levels for the map should be stable after 2 to 4-month mapping.

Adolescent↗