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Investigation of the complex descending innervation of the dorsal cochlear nucleus in the rat: a transneuronal tract-tracing study using pseudorabies virus.

The afferent neuronal connections of the dorsal cochlear nucleus were investigated in rats by using a trans-synaptic retrograde tract-tracing method. The neurotropic viral tracer, the Bartha strain of the pseudorabies virus was stereotaxically injected into the dorsal cochlear nucleus, ipsilaterally. Neurons, which project directly or indirectly (one or multiple relays by other neurons) to the dorsal cochlear nucleus were infected and visualized by immunohistochemistry. Labeled neurons were found in each components of the auditory pathway, some of the monoaminergic cell groups in the lower brainstem, the hypothalamus and in some limbic areas.

Animals↗

Cellular regulatory mechanisms influencing the activity of the cochlear nucleus: a review.

The cochlear nucleus is the site in the auditory pathway where the primary sensory information carried by the fibres of the acoustic nerve is transmitted to the second-order neurones. According to the generally accepted view this transmission is not a simple relay process but is considered as the first stage where the decoding of the auditory information begins. This notion is based on the diverse neurone composition and highly ordered structure of the nucleus, on the complex electrophysiological properties and activity patterns of the neurones, on the activity of local and descending modulatory mechanisms and on the presence of a highly sophisticated intracellular Ca2+ homeostasis. This review puts emphasis on introducing the experimental findings supporting the above statements and on the questions which should be answered in order to gain a better understanding of the function of the cochlear nucleus.

Animals↗

Subcortical correlates of the auditory brain stem potentials in the monkey: bipolar EEG and multiple unit activity responses.

Bipolar EEG and multiple unit activity (MUA) responses correlated to the vertex auditory brain stem potentials (ABSP) were recorded in different brain stem and diencephalic primary auditory pathways and other anatomically related structures of large monkeys under barbiturate anesthesia. Bipolar EEG responses were recorded bilaterally to monaural stimulation and were formed by 3 or more of 6 consecutive components labeled A, B, C, D, E and F (peak latencies of 3.8, 4.2, 4.6, 5.0, 7.8 and 11.8 msec) correlated in latency with waves III, IV, V, VI, VII and SP3 of the ABSP, respectively. Component B was prominent and showed clearcut reverse polarity at the trapezoid body (TB) and superior olivary complex (SOC), while components C and F inverted and everted polarity at the mesencephalic reticular formation (MRF) and medial geniculate nucleus thalami (MG). Subcortical MUA peaks A, B, C, D and E time locked to the stimulus presentation correlated in latency to those of the bipolar EEG responses. In addition, a significant correlation was found between percentage amplitude of the subcortical EEG response components and MUA peaks in different structures contra- (r = 0.847) and ipsilateral (r = 0.973) to the stimulated ear. Although a single wave of the vertex ABSP correlated in latency with more than one response component in different subcortical loci, amplitude of component A was significantly larger (P less than or equal to 0.02) at TB ipsilateral, B at TB and SOC bilateral, and C and F at MRF, and D and E at MG contralateral to the stimulated ear.

Acoustic Stimulation↗

Neurobiological specializations in echolocating bats.

Although the bat's nervous system follows the general mammalian plan in both its structure and function, it has undergone a number of modifications associated with flight and echolocation. The most obvious neuroanatomical specializations are seen in the cochleas of certain species of bats and in the lower brainstem auditory pathways of all microchiroptera. This article is a review of peripheral and central auditory neuroanatomical specializations in echolocating bats. Findings show that although the structural features of the central nervous system of echolocating microchiropteran bats are basically the same as those of more generalized mammals, certain pathways, mainly those having to do with accurate processing of temporal information and auditory control of motor activity, are hypertrophied and/or organized somewhat differently from those same pathways in nonecholocating species. Through the resulting changes in strengths and timing of synaptic inputs to neurons in these pathways, bats have optimized the mechanisms for analysis of complex sound patterns to derive accurate information about objects in their environment and direct behavior toward those objects.

Animals↗

C-fos expression after single and kindled audiogenic seizures in Wistar rats.

In naive Wistar rats susceptible to sound, a single audiogenic seizure induced the expression of c-fos in the subcortical auditory nuclei whereas the forebrain was almost completely devoid of any labelling. After kindling of audiogenic seizures by 40 daily exposures to sound, the seizure induced a strong c-fos expression in the amygdala, the piriform cortex, the hippocampus and the neocortex. These results confirm: (1) that audiogenic seizures are brain-stem seizures related to dysfunction of auditory pathways, and (ii) that kindling of audiogenic seizures recruits forebrain and limbic structures into the seizure network.

Acoustic Stimulation↗

Sensorineural hearing loss during development: morphological and physiological response of the cochlea and auditory brainstem.

We have investigated the effects of sensorineural hearing loss on the cochlea and central auditory system of profoundly deafened cats. Seventeen adult cats were used: four had normal hearing; 12 were deafened neonatally for periods of < 2.5 years (five bilaterally, seven unilaterally); and one animal had a long-term (approximately 8 years) profound bilateral hearing loss. Bipolar scala tympani stimulating electrodes were bilaterally implanted in each animal, and electrically evoked auditory brainstem responses (EABRs) were recorded in an acute study to evaluate the basic physiologic response properties of the deafened auditory pathway. The cochleae and cochlear nuclei (CN) of each animal were examined with light microscopy. Spiral ganglion cell density in neonatally deafened cochleae was 17% of normal, and only 1.5% of normal in the long-term deaf animal. There was a 46% reduction in total CN volume in neonatally deafened animals compared to normal, and a 60% reduction in the long-term deaf animal. Neural density in the anteroventral CN of bilaterally deafened animals was 37% higher than normal; 44% higher in the long-term deaf animal. Significantly, however, we saw no evidence of a loss of neurones within the anteroventral CN in any deafened animal. There was a significant increase in EABR threshold and wave IV latency in the deafened animals, and a significant decrease in response amplitude and input/output function gradient. Again, these changes were more extensive in the long-term deaf animal. These data show that a sensorineural hearing loss can evoke significant morphological and physiological changes within the cochlea and auditory brainstem, and these changes become greater with duration of deafness. It remains to be seen whether these changes can be reversed following the introduction of afferent activity via chronic electrical stimulation of the auditory nerve.

Action Potentials↗

Inhibition of auditory cortical responses to ipsilateral stimuli during dichotic listening: evidence from magnetoencephalography.

The present magnetoencephalography (MEG) study on auditory evoked magnetic fields (AEFs) was aimed at verifying whether during dichotic listening the contralateral auditory pathway inhibits the ipsilateral one, as suggested by behavioural and patient studies. Ten healthy subjects were given a randomized series of three complex tones (261, 293 and 391 Hz, 500 ms duration), which were delivered monotically and dichotically with different intensities [60, 70 or 80 dBA (audio decibels)]. MEG data were recorded from the right auditory cortex. Results showed that the M100 amplitude over the right auditory cortex increased progressively when tones of increasing intensity were provided at the ipsilateral (right) ear. This effect on M100 was abolished when a concurrent tone of constant intensity was delivered dichotically at the contralateral (left) ear, suggesting that the contralateral pathway inhibited the ipsilateral one. The ipsilateral inhibition was present only when the contralateral tone fundamental frequency was similar to the ipsilateral tone. It was proposed that the occlusion mechanism would be exerted in cortical auditory areas as the dichotic effects were observed at M100 but not M50 component. This is the first evidence showing a neurophysiological inhibition driven by the contralateral auditory pathway over the ipsilateral one during dichotic listening.

Acoustic Stimulation↗

Chronic and acute transtentorial herniation with tumours of the posterior cranial fossa.

In patients with expanding lesions of the posterior fossa general hyper-reflexia (and bilateral latency shifts of auditory evoked brain stem potentials) have been noted as possible symptoms of chronic ascending transtentorial herniation. After ventricular tap, this chronic herniation may evolve into acute herniation with progressive reduction of consciousness which in our experience can only be survived by decompression of the compressed brain stem. The chronic transtentorial herniation is related morphologically to demyelination of the pyramidal tracts and the auditory pathways, whereas the acute transtentorial herniation is related to microcirculatory disturbances in the reticular formation of the mesencephalo-pontine junction.

Auditory Pathways↗

Neuronal substrates involved in processing of communicative acoustic signals in tree shrews: a 2-deoxyglucose study.

Autoradiography with [14C]2-deoxyglucose (2-DG) was used to map functional differences in activation of the central auditory pathway in adult tree shrews during presentation of particular acoustic stimuli (low frequency, LFS, and high frequency, HFS, pure sinus tones; social calls, SC). Individuals stimulated with broadband-noise (BBN) were used as controls. Stimulus-specific labelling was found in autoradiographs of cochlear nucleus, superior olivary complex, inferior colliculus and auditory cortex. These findings imply a tonotopic organization at least in these auditory brain areas and indicate differences in the processing of sounds with different functional significance.

Acoustic Stimulation↗

Distribution of GABAA, GABAB, and glycine receptors in the central auditory system of the big brown bat, Eptesicus fuscus.

Quantitative autoradiographic techniques were used to compare the distribution of GABAA, GABAB, and glycine receptors in the subcortical auditory pathway of the big brown bat, Eptesicus fuscus. For GABAA receptors, the ligand used was 35S-t-butylbicyclophosphorothionate (TBPS) for GABAB receptors, 3H-GABA was used as a ligand in the presence of isoguvacine to block binding to GABAA sites; for glycine, the ligand used was 3H-strychnine. In the subcortical auditory nuclei there appears to be at least a partial complementarity in the distribution of GABAA receptors labeled with 35S-TBPS and glycine receptors labeled with 3H-strychnine, GABAA receptors were concentrated mainly in the inferior colliculus (IC) and medial geniculate nucleus, whereas glycine receptors were concentrated mainly in nuclei below the level of the IC. Within the IC, there was a graded spatial distribution of 35S-TBPS binding; the most dense labeling was in the dorsomedial region, but very sparse labeling was observed in the ventrolateral region. There was also a graded spatial distribution of 3H-strychnine binding. The most dense labeling was in the ventral and lateral regions and the weakest labeling was in the dorsomedial region. Thus, in the IC, the distribution of 35S-TBPS was complementary to that of 3H-strychnine. GABAB receptors were distributed at a low level throughout the subcortical auditory nuclei, but were most prominent in the dorsomedial part of the IC.

Animals↗

Expression of AMPA receptor subunit flip/flop splice variants in the rat auditory brainstem and inferior colliculus.

The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit mRNAs and their flip/flop splice variants was evaluated in the rat auditory brainstem and inferior colliculus employing in situ hybridization with radiolabeled oligonucleotide probes. A differential expression of AMPA receptor subunits in auditory nuclei was observed. In general, neurons in all nuclei of the auditory brainstem express high levels of GluR-C flop and GluR-D flop mRNA, but low to very low levels of GluR-A and GluR-B mRNA. The strongest GluR-C and -D flop expression is found in the ventral and medial part of the anteroventral cochlear nucleus, the posteroventral cochlear nucleus, and the medial and the lateral superior olive. These nuclei are part of the binaural auditory pathway which is important for sound localization in space. In contrast, neurons in the central nucleus of the inferior colliculus express high levels of GluR-B flip but only low levels of the other AMPA receptor subunits. From our data, we conclude that neurons of nuclei involved in binaural processing exhibit a specific "auditory AMPA receptor" which consists primarily of GluR-C flop and -D flop and often lacks GluR-B subunits; this indicates fast kinetics and high Ca(2+) permeability of AMPA receptor currents. In contrast, neurons in the central nucleus of the inferior colliculus contain large amounts of GluR-B flip subunits resulting in Ca(2+) impermeable AMPA receptors with slow kinetics.

Animals↗

Simultaneous recording of fast and slow auditory evoked potentials (slow-fast-simultaneous-ERA, SFS-ERA).

In order to reduce measurement time we have used part of the interstimulus interval of the slow cortical responses to record fast brain stem responses. For this purpose we reconstructed a programmable audiometer and preamplifier which are controlled by a computer. These, with 1/4 ms-click and tone-burst stimulation simultaneously gained fast and slow responses, not only give a frequency-related view of the threshold and the kind of hearing loss--because of amplitude and latency--, but also in some cases--because of differences between both responses--give ideas of the possible location of the hearing impairment through the auditory pathways. The audiological value of this new method is discussed and explained by giving examples of two interesting cases, one central-neural hearing loss and one questionable aggravation.

Acoustic Stimulation↗

Origin of ascending projections to inferior colliculus in the mustache bat, Pteronotus parnellii.

The origins of pathways to the inferior colliculus of the mustache bat were identified by retrograde transport of horseradish peroxidase (HRP). A specific goal of this study was to obtain evidence that would help determine whether the nuclei, shown in the previous paper to have unusual cytoarchitectural features, are unique to bats, or whether they are homologous to areas that are not well differentiated in other mammals. The auditory pathways in the lower brain stem of Pteronotus appear to conform to the same basic organization as in other mammals: After injection of HRP into one inferior colliculus, labeled cells are located contralaterally in the cochlear nucleus, ipsilaterally in the medical superior olive, bilaterally in the lateral superior olive, ipsilaterally in the ventral and intermediate nuclei of the lateral lemniscus, and bilaterally in the dorsal nucleus of the lateral lemniscus. These patterns of labeling provide a basis for understanding how the specialized auditory areas of the bat may be organized within a basic plan of mammalian auditory systems. In the anteroventral cochlear nucleus the unusually small spherical cells seem to be homologous to stellate cells in the anteroventral cochlear nucleus of the cat. In the superior olive, differences in patterns of labeled cells distinguish the medial from the lateral superior olive. In the lateral lemniscus the pattern of labeled cells shows clear differences between the two special parts, intermediate and ventral nuclei, as well as between these and the dorsal nucleus of the lateral lemniscus. The results are consistent with the hypothesis that the unusual auditory nuclei of the bat have homologues in mammals whose auditory systems are not specialized for echolocation.

Animals↗

Sounds with harmonic spectra are more effective than pure tones in inducing audiogenic seizure in rats.

Twenty rats of an audiogenic seizure (AGS)-susceptible stock were exposed to four different sound stimuli and seizure severity and seizure-latency were registered. Two sounds with harmonic spectra, one pure tone and band noise were used. The harmonic spectra were found to be significantly (P less than 0.005) more effective than the other stimuli in inducing AGS when seizure-latency was taken as a parameter. Connections from the auditory pathway to the reticular formation seem to be of importance in the triggering of these seizures. AGS-susceptible rats may offer a useful tool for experimental hearing research.

Acoustic Stimulation↗

Hair cell regeneration in the chick basilar papilla after exposure to wide-band noise: evidence for ganglion cell involvement.

It has been demonstrated that the auditory epithelium in the chick basilar papilla may regenerate after acoustic or ototoxic damage. Both types of damage may elicit the appearance of new cells that may develop in to the sensory cells. Factors inducing this process and the role of ganglion cells, the first neuron cells in the auditory pathway, are still unknown. The pattern of auditory damage and regeneration, after octave-band and pure-tone noise exposure, has been well established in research studies on chicks, but there are scarce data on wide-band noise effects. The aim of this study was to investigate the effect of wide-band noise, with different exposure levels applied, on the chick basilar papilla and supporting cells. Further, it was also aimed to determine whether the proliferation of ganglion cells, after wide-band noise exposure, occurs. The morphological changes were assessed with fluorescent, light, and transmission electron microscopy. Cell proliferation was studied based on immunoreactivity assays of proliferating cell nuclear antigen (PCNA). The exposure to wide-band noise at 120 dB SPL for 72 h produced stripe-like lesion of tall hair cells along the neural edge of the basilar papilla, mainly in the middle and, at the lesser extend, in its proximal part. There was no patch-like damage to the region of short hair cells, commonly observed after the exposure to the octave-band or pure-tone noise. The lesion extend depended on the level of exposure. The lower equivalent levels of noise (120 dB SPL for 40 h intermittent exposure) produced proportionally less damage. No morphological changes at light and fluorescent microscopy (apart from tectorial membrane exfoliation) were observed at 110 dB SPL in case of 20 h intermittent exposure. The elimination of dying hair cells took place either by pulling a damaged cell down to the basilar membrane or by extruding the cell to the subtectorial space. New hair cells reappeared at the sensory epithelium on the fifth day after the end of exposure. Cell proliferation started prior to hair cell loss. PCNA-like immunoreactivity was observed after the exposure at all levels in both the damaged and intact areas. PCNA appeared not only in the supporting cells, as indicated in previous studies, but also in the ganglion cells, suggesting ganglion cell involvement in the process of regeneration.

Acoustic Stimulation↗

Acute effect of nicotine on non-smokers: II. MLRs and 40-Hz responses.

This paper is the second in a series of three investigating the role of cholinergic mechanisms in the auditory system by assessing the acute effects of nicotine, an acetylcholinomimetic drug, on aggregate responses within the auditory pathway. In a single-blind procedure, auditory responses were obtained from 20 normal-hearing, non-smokers (10 male) under two conditions (nicotine, placebo). The effects of nicotine on central, mesogenous responses of the auditory system (middle latency and 40-Hz responses) are described in this second paper. Results indicated that transdermal administration of nicotine to non-smokers does significantly affect the central, neural transmission of acoustic information. Na-Pa amplitude and Nb latency of the middle latency response and latency measures of the 40-Hz response were acutely altered by the presence of nicotine.

Acoustic Stimulation↗

Dissecting the frog inner ear with Gaussian noise. I. Application of high-order Wiener-kernel analysis.

Wiener kernel analysis was used to characterize the auditory pathway from tympanic membrane to single primary auditory nerve fibers in the European edible frog, Rana esculenta. Nerve fiber signals were recorded in response to white Gaussian noise. By cross-correlating the noise stimulus and the nerve fiber response, we computed (1) the full second-order Wiener kernel, and (2) the diagonals of the zeroth- to fourth-order Wiener kernels. These diagonals are usually referred to as polynomial correlation functions. The measured Wiener kernels were fitted with a 'sandwich' model. A new fitting procedure was used to compute the response characteristics of (1) the first filter, (2) the static nonlinearity, and (3) the second filter, which form the functional components of the model. The first filter is a bandpass filter. In the majority of low frequency fibers, with best excitatory frequency (BEF) < 800 Hz, this filter was tuned to two frequencies. This dual tuning mechanism gives rise to 'off-diagonal' components in the second-order Wiener kernel. The static nonlinearity resembles a rectifier, and is dominated by second-order (quadratic) nonlinearity. As a function of BEF, the shape of the nonlinearity changes systematically. Finally, the last filter in the model was a low pass filter. Across fibers, its cutoff frequency f-3dB ranged from 106 to 434 Hz.

Acoustic Stimulation↗

Electrophysiological evidence of persisting unilateral auditory cortex dysfunction in the late outcome of Landau and Kleffner syndrome.

OBJECTIVES: In the late outcome of Landau and Kleffner syndrome (LKS), a childhood-acquired epileptic aphasia, most patients show after complete recovery of epilepsy a permanent one-ear extinction on dichotic listening tests contralateral to the temporal cortex previously affected by the epileptic focus. The pathophysiological significance of this dichotic extinction is not yet understood. It may be a consequence of a permanent dysfunction in the auditory system due to epileptic activity during the maturing period of the auditory system. Evoked potentials were used to check this hypothesis and to localize the level of the dysfunction along the auditory pathways. METHODS: Early, middle latency and late auditory evoked potentials were recorded in 5 right-handed children having recovered from LKS. They were compared with those of 5 control children paired for age and gender. RESULTS: In all 5 LKS patients, early and middle latency auditory evoked potentials were normal. But the amplitude of N1c (arising from associative auditory areas) was strongly reduced at temporal electrodes contralateral to the extinguished ear, whereas latency and amplitude of N1b (related to primary auditory areas) were in the normal range. CONCLUSIONS: Unilateral voltage reduction of late auditory evoked potentials over the temporal areas previously involved by epileptic discharges suggests a permanent dysfunction in the associative auditory cortex, the behavioral expression of which is the unilateral dichotic extinction.

Adolescent↗