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PubMed1995

Sound stimulation induces Fos-related antigens in cells with common morphological properties throughout the auditory brainstem.

Cells within the auditory brainstem of cat that respond to sound by producing the transcription factor Fos or related proteins were identified by immunostaining with antisera against Fos and Zif/268. Within the cochlear nucleus, all antisera showed similar staining patterns, however, in the superior olive and inferior colliculus, staining patterns differed between antisera. Immunostained cells were characterized by their size, location, by the presence of perisomatic terminals that immunostained for glutamate decarboxylase or synaptophysin, or by electron microscopy. Most cell classes were not immunopositive. In the ventral cochlear nucleus, roughly 99% of Fos-positive cells had few perisomatic terminals. Within the superior olivary complex (SOC), the majority of immunopositive cells had few perisomatic terminals. Lateral olivocochlear cells were identified as Fos positive by their size, location, lack of perisomatic terminals, and positive costaining for acetylcholinesterase as evidenced by a novel reaction product. This report appears to be the first demonstration of these cells responding to sound stimulation. Within the inferior colliculus, bands of positive cells produced by tonal stimulation extended from the central nucleus throughout the dorsal cortex and the posterior pericentral region, a finding unexpected on the basis of previous electrophysiological recordings and anatomical studies of ascending inputs to the colliculus. Approximately 35% of Fos-positive cells in the inferior colliculus had plentiful perisomatic terminals. Results demonstrate a high degree of specificity of auditory cell types that respond to sound by producing Fos-like proteins and show that previously intractable physiological questions can be addressed by assaying for sound-induced production of these antigens.

Acoustic Stimulation↗
PubMed2004

A phenomenological model of peripheral and central neural responses to amplitude-modulated tones.

A phenomenological model with time-varying excitation and inhibition was developed to study possible neural mechanisms underlying changes in the representation of temporal envelopes along the auditory pathway. A modified version of an existing auditory-nerve model [Zhang et al., J. Acoust. Soc. Am. 109, 648-670 (2001)] was used to provide inputs to higher hypothetical processing centers. Model responses were compared directly to published physiological data at three levels: the auditory nerve, ventral cochlear nucleus, and inferior colliculus. Trends and absolute values of both average firing rate and synchrony to the modulation period were accurately predicted at each level for a wide range of stimulus modulation depths and modulation frequencies. The diversity of central physiological responses was accounted for with realistic variations of model parameters. Specifically, enhanced synchrony in the cochlear nucleus and rate-tuning to modulation frequency in the inferior colliculus were predicted by choosing appropriate relative strengths and time courses of excitatory and inhibitory inputs to postsynaptic model cells. The proposed model is fundamentally different than others that have been used to explain the representation of envelopes in the mammalian midbrain, and it provides a computational tool for testing hypothesized relationships between physiology and psychophysics.

Acoustics↗
PubMed1995

Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization.

This study was concerned with the distribution of a variety of putative neuromodulator and neurotransmitter systems in auditory regions of the rat brainstem using in situ hybridization histochemistry. Serial brain sections were screened for the presence of mRNAs for (i) precursors of the neuroactive substances cholecystokinin, somatostatin, proenkephalin and substance P (preprotachykinin), (ii) glutamic acid decarboxylase, the key synthesizing enzyme for GABA, or (iii) subunits alpha 1, alpha 2 and alpha 3 of the GABAA receptor. Detectable message for all of these probes was found in at least one auditory brainstem area. There were clear differences in the distribution of the various mRNAs in subregions of the inferior colliculus, superior olivary complex, lateral lemniscus and cochlear nucleus. Cells expressing mRNA for glutamic acid decarboxylase were most prominent in the inferior colliculus, but were also present in all lower auditory brainstem nuclei, except the medial superior olivary nucleus and medial nucleus of trapezoid body. The mRNA for GABAA alpha 1 receptor subunits was detectable in all auditory regions investigated, although at different levels of expression. GABAA alpha 2 and alpha 3 mRNA signals were seen in inferior colliculus, lateral lemniscus and in almost all superior olivary complex regions, but in fewer cells and at lower levels than the GABAA alpha 1 subtype. Moderate to high levels of preprocholecystokinin mRNA expression were seen in all subregions of the inferior colliculus. In other auditory brainstem areas, preprocholecystokinin mRNA levels were either low or absent. With regard to mRNAs for the neuroactive peptides somatostatin, preprotachykinin and preproenkephalin, all were expressed in the inferior colliculus but there were differences in their cellular distribution. For example, there were almost no preprotachykinin mRNA expressing cells in the central nucleus of inferior colliculus and levels of somatostatin mRNA were especially high in the dorsal cortex and in layer 3 of the external cortex of inferior colliculus. There were also differences in the pattern of expression of these mRNAs in the various brainstem auditory nuclei; there was no preprotachykinin mRNA in any part of the superior olivary complex, only somatostatin mRNA was found in the ventral cochlear nucleus, and expression of preproenkephalin mRNA was pronounced in the ventral nucleus of the trapezoid body and the rostral periolivary zone. The data are considered in light of the connectivity and functional organization of the auditory brainstem.

Animals↗
PubMed2005

Fluorescent labeling of rat auditory brainstem circuits for synaptic and electrophysiological studies.

We visualized neurons with fluorescent agents, both retrogradely and anterogradely, to identify the input and output neuronal pathways in the rat auditory system. Output neurons of dorsal cochlear nucleus (DCN) were labeled retrogradely by injecting fluorescent microspheres into the inferior colliculus. Electrical recordings were made from the labeled fusiform cells of DCN with the whole-cell patch-clamp recording technique in slice preparations. DiI and Sindbis virus expressing membrane-targeted green fluorescent protein (GFP) were adopted for anterograde labeling. Auditory nerve fibers (ANFs) were labeled by injecting DiI into the cochlea, and the contralateral projection to the medial nucleus of the trapezoid body (MNTB) by injecting DiI and GFP into the ventral cochlear nucleus. A single ANF projecting to a DCN fusiform cell was electrically stimulated by a glass electrode and EPSCs were recorded using whole-cell patch-clamp recording methods. EPSCs were sensitive to the positioning of the electrode, and the size of EPSCs was constant irrespective of stimulus intensity, indicating that a single fiber was stimulated. Large EPSCs were generated from MNTB principal cells by stimulating the labeled fiber with a Calyx of Held terminal. The membrane excitability and EPSCs recorded after fluorescence labeling were similar to those previously reported. We confirm that the fluorescence labeling is effective to visualize neural networks and is useful to investigate the electrophysiological properties of neurons and synapses.

Animals↗
PubMed1998

Specific sound-induced noradrenergic and serotonergic activation in central auditory structures.

We have studied the noradrenergic and serotonergic changes induced by white noise stimulation at 70, 90 or 110 dB SPL for 45 min, in cochlear nuclei, inferior colliculus (IC), primary auditory cortex (PAC) and as a comparison in locus coeruleus (LC) and raphe dorsalis using HPLC. Both noradrenergic and serotonergic pathways were activated in the dorsal+posteroventral cochlear nuclei (DCN+PVCN) without changes in the anteroventral cochlear nucleus (AVCN) and IC. In the DCN+PVCN the noradrenergic activation was restricted to animals exposed to 70 dB SPL whereas the increase of serotonin content was intensity-dependent. In PAC serotonergic activation was observed only after 70 dB SPL exposure. These data suggest that in physiological conditions (70 dB SPL) noradrenergic and serotonergic regulation of the processing of auditory information occurs specifically in the dorsal cochlear nucleus where the control of incoming information to higher auditory structures takes place (i.e. IC and PAC). We suggest that the serotonergic activation in the primary auditory cortex for 70 dB SPL sound stimulation could be related to the fact that low-intensity white noise stimulation could be the most plastic-demanding processing in the auditory cortex.

Acoustic Stimulation↗
PubMed2004

Fast inhibition alters first spike timing in auditory brainstem neurons.

Within the first processing site of the central auditory pathway, inhibitory neurons (D stellate cells) broadly tuned to tonal frequency project on narrowly tuned, excitatory output neurons (T stellate cells). The latter is thought to provide a topographic representation of sound spectrum, whereas the former is thought to provide lateral inhibition that improves spectral contrast, particularly in noise. In response to pure tones, the overall discharge rate in T stellate cells is unlikely to be suppressed dramatically by D stellate cells because they respond primarily to stimulus onset and provide fast, short-duration inhibition. In vivo intracellular recordings from the ventral cochlear nucleus (VCN) showed that, when tones were presented above or below the characteristic frequency (CF) of a T stellate neuron, they were inhibited during depolarization. This resulted in a delay in the initial action potential produced by T stellate cells. This ability of fast inhibition to alter the first spike timing of a T stellate neuron was confirmed by electrically activating the D stellate cell pathway that arises in the contralateral cochlear nucleus. Delay was also induced when two tones were presented: one at CF and one outside the frequency response area of the T stellate neuron. These findings suggest that the traditional view of lateral inhibition within the VCN should incorporate delay as one of its principle outcomes.

Acoustic Stimulation↗
PubMed1999

A morphological study of the cochlear nuclei of the pigeon (Columba livia).

The pigeon cochlear nucleus angularis (NA) and nucleus magnocellularis (NM) were analyzed with Golgi and Nissl techniques. NA was divided into a medial NAm and NA proper, which could be subdivided further into an intermediate NAi and lateral NAl. NAm contained a mostly homogeneous population of a unique multipolar cell type with very short dendrites and large somatic spines. NA proper contained four cell types: large, medium, and small multipolars, and medium bipolar. The medium multipolar cells were most common, and resembled the multipolar cells of the mammalian ventral cochlear nucleus. NM presented a homogenous appearance with a mediolateral gradient of cell size and shape. Medially located higher best frequency NM principal cells had round cell bodies with small somatic spines and few dendrites. By comparison, laterally located low best frequency NM stellate cells had more dendrites and spindle shaped cell bodies. The similarities between the cell types of NA and the cell types in the cochlear nuclei of other amniote vertebrates may be due to homology or convergent evolution.

Animals↗
PubMed1999

Topographic anatomy of the cochlear nuclear region at the floor of the fourth ventricle in humans.

OBJECT: The development of appropriate methods to stimulate the dorsal and ventral cochlear nucleus by means of an auditory brainstem implant in patients with acquired bilateral anacusis requires a detailed topoanatomical knowledge both of the location and extension of the nuclear surface in the fourth ventricle and lateral recess and of its variability. The goal of this study was to provide that information. Anatomically, it is possible to use a midline surgical approach to the fourth ventricle rather than the translabyrinthine and suboccipital routes of access used hitherto. This is especially useful if severe scarring, which occurs as a result of tumor removal in the cerebellopontine angle, make the orientation and placement of an auditory brainstem implant via a lateral surgical approach difficult. There have been only a few studies, involving single cases and small series of patients, in which the focus was the exact extension of the cochlear nuclei, whose microsurgically relevant position in relation to the surface structures is not known in detail. METHODS: Landmarks that are important for the placement of an auditory brainstem implant through the fourth ventricle were examined and measured in a large series of 28 formalin-fixed human brainstems. In all cases, these examinations were supplemented by addition of a histological section series. For the first time values of unfixed fresh brainstem tissue were determined. Anatomical features are discussed with regard to their possible neurosurgical relevance, taking into account inter- and intraindividual variability. CONCLUSIONS: The midline approach would provide an opportunity to stimulate the whole area of the dorsal as well as the ventral cochlear nucleus with an auditory brainstem implant.

Adult↗
PubMed1990

Prenatal development of the cochlear nerve in the albino rat.

Twenty-eight prenatal (14 to 20 days) Wistar albino rats were studied with Cajal-de Castro's silver reduced stain. The histological sections were oriented in a parasagittal oblique plane, parallel to the cochlear root, in order to observe the origin, course and destination of the cochlear fibres in as few consecutive sections as possible. In all the prenatal days studied, the fibres arising in the first half coil of the cochlea (hook's bundle), show a different orientation than those of the other cochlear nerve fibres, which constitute the spiralized bundle, originating in the basal, medial and apical portions of the cochlea. The hook-bundle does not participate in the curling of the cochlear nerve and it describes a particular course. At first, its fibres are situated in a lateral position in the nerve when it is inside the internal auditive duct. Then, the hook-fibres take a postero-inferior position just at the entry of the bulbar cochlear nuclei region. Furthermore, we have seen no hook's afferents branching in the ventral cochlear nucleus, and it could be suggested that these fibres project directly to the superficial dorso-medial area of the postero-ventral cochlear nucleus.

Animals↗
PubMed1988

Distribution of protein kinase C-like immunoreactive neurons in rat brain.

Distribution of protein kinase C in the CNS of rat is presented based on immunohistochemical analysis with monoclonal antibodies against this protein kinase. Protein kinase C-like immunoreactivity was discretely localized and associated with neurons. Most, if not all, glial cells were not significantly stained. The greatest density of the immunoreactive material was seen in the following regions: the olfactory bulb (external plexiform layer), olfactory tuberculum, anterior olfactory nucleus, cerebral cortex (layers I and IV), pyriform cortex, hippocampus (strata radiatum and oriens), amygdaloid complex (central and basolateral nuclei), cerebellar cortex (molecular layer), dorsal cochlear nucleus, nucleus spinal tract of the trigeminal nerve, and dorsal horn of the spinal cord (substantia gelatinosa). Image analysis revealed that the regional distribution of the protein kinase C-like immunoreaction generally agreed with that of phorbol ester-binding sites. Immunoreactive perikarya were found in the following areas: the cerebral cortex (layers V and VI), caudate putamen, hippocampus, thalamus, amygdaloid complex, medial and lateral geniculate nucleus, superior colliculus, cerebellar cortex, nucleus spinal tract of the trigeminal nerve, dorsal cochlear nucleus, and dorsal horn of the spinal cord. Intense protein kinase C-like immunoreactivity in the neuron was observed both in the membrane and cytoplasm of the perikarya, dendrites, axons, and axon terminals, while weak immunoreaction was seen in the nuclei but almost never in the nucleoles. A map of protein kinase C-containing neurons was constructed. Such an uneven distribution in the brain suggests that this enzyme may play roles in controlling neuronal function in the areas noted.

Animals↗
PubMedDate not supplied

Glutamate neurotoxicity in rat auditory system: cochlear nuclear complex.

In other systems such as the hypothalamus and hippocampus, it has been shown that cells postsynaptic with respect to glutamatergic inputs degenerate when exposed to large doses of glutamate ("glutamate neurotoxicity"). We have shown that large doses of glutamate administered intraperitoneally are toxic to spiral ganglion cells in the inner ear of the rat. In the present study, we have investigated whether similar levels of glutamate cause alterations in the neurons of the cochlear nuclei. Specifically, we have studied the morphology and size of the cochlear nuclear complex and its subdivisions as well as the size and density of cochlear nucleus neurons following administration of glutamate. The morphological evidence indicates that glutamate caused severe anatomical alteration of the cochlear nuclei. The changes were most pronounced in the anteroventral cochlear nucleus, especially in the neurons that receive terminals of the end bulbs of Held from the cochlear nerve. This could be a direct effect of glutamate in the cochlear nuclei or secondary to degeneration of cochlear nerve fibers in the inner ear.

Animals↗
PubMed2004

Loss of GLUR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor subunit differentially affects remaining synaptic glutamate receptors in cerebellum and cochlear nuclei.

The alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) type of ionotropic glutamate receptor is the major mediator of fast neurotransmission in the brain and spinal cord. Most AMPA receptors are impermeable to calcium because they contain the GluR2 subunit. However, some AMPA receptors lack GluR2 and pass calcium which can mediate synaptic plasticity and, in excess, neurotoxicity. Previously, we showed a decrease in the density of synaptic AMPA receptors in the hippocampus of mice lacking GluR2. In this study, using these GluR2-lacking mice, we examined other areas of the brain that differ in the amount of GluR2 normally present. Like hippocampal spines, cerebellar Purkinje spines normally express AMPA receptors with high GluR2 and showed a decrease in synaptic AMPA receptors in mutant mice. In contrast, neurons that normally express AMPA receptors with little or no GluR2, such as in the anteroventral cochlear nucleus, showed no decrease in AMPA receptors and even showed an increase in one AMPA receptor subunit. These two different patterns may relate to preadaptations to prevent calcium neurotoxicity; such mechanisms might be absent in Purkinje and hippocampal spines so that these neurons must decrease their total expression of synaptic AMPA receptors (calcium permeable in mutant mice) to prevent calcium neurotoxicity. In addition, we found that another glutamate receptor, GluRdelta2, which is abundant only in parallel fibre synapses on Purkinje cells and in the dorsal cochlear nucleus, is up-regulated at these synapses in mutant mice; this probably reflects some change in GluRdelta2 targeting to these synapses.

Animals↗
PubMed1988

Neural connections identified with PHA-L anterograde and HRP retrograde tract-tracing techniques.

This paper describes a method of identifying specific input and output elements of a two-neuron projection pathway. Phaseolus vulgaris leucoagglutinin (PHA-L) anterograde tract-tracing was used in combination with the retrograde transport of horseradish peroxidase (HRP) to demonstrate connections between small groups of neurons in the brainstem auditory system. Specifically, the projection from cochlear nucleus to olivary neurons that project to the cochlea were demonstrated. The first neuron in this pathway (the cochlear nucleus neuron) was anterogradely labelled with PHA-L and could be traced via labelled axons and terminals to the second neuron (the olivocochlear neuron) whose soma was labelled with HRP after cochlear injection.

Animals↗
PubMed1998

[Oto-neuro-surgical approach and accessibility to the cochlear nuclei. Significance in auditory brain stem implant].

The auditory brainstem implant (ABI) is now used to stimulate the cochlear nucleus to obtain auditory perception in patients with type 2 neurofibromatosis. Only electrical stimulation of the cochlear nucleus complex, in the lateral recess of the fourth ventricle, can achieve auditory rehabilitation of these profound bilateral retrocochlear deafness. With 20 standard translabyrinthine approaches, our personal anatomical study propose to describe surgical landmarks of the cochlear nuclear complex and surgical accessibility of the lateral recess of the fourth ventricle. The root of vestibulocochlear nerve, the glossopharyngeal nerve and the choroid plexus of the fourth ventricle might have surgical significance because of their reliability.

Brain Stem↗
PubMed2002

The cellular origin of corticofugal projections to the superior olivary complex in the rat.

Corticofugal pathways originating in auditory cortex innervate most subcortical auditory nuclei in the ascending pathway [Auditory Neurosci. 1 (1995) 287-308; J. Comp. Neurol. 371 (1996) 15-40]. Our goal is to determine if these projections arise from the same neurons or if different neurons project to each of the separate structures. We also seek to identify the layers and fields of auditory cortex from which these neurons originate. In the present study, we answer these questions with respect to the projections to the superior olivary complex (SOC). Fluorescent retrograde tracers, Fast Blue (FB) or Diamidino Yellow (DiY), were injected into the SOC and the pattern of labeled cells was determined in temporal neocortex. We also injected FB into the granule cell domain (GCD) of the cochlear nucleus. Cortical projections to the GCD derive exclusively from layer V pyramidal cells in primary auditory cortex [Brain Res. 706 (1996) 97-102]. Thus the pattern of labeling produced by injections in the GCD provided a reference for interpreting the labeling after SOC injections. Layer V pyramidal cells project to the SOC, and these neurons were distributed bilaterally in primary and secondary areas of auditory cortex. The projections to the SOC from primary auditory cortex are predominantly uncrossed, whereas those from secondary auditory cortex are nearly equal for the two hemispheres. In animals that received injections of FB in the GCD and DiY in the SOC, cells labeled by each injection had a different laminar distribution and very few cells were double labeled. These data suggest that the cortical pathways ending in the cochlear nucleus and SOC are largely independent. We discuss the implications of these findings with respect to the multifunctional nature of the SOC in brainstem auditory processing.

Amidines↗
PubMed1991

Details of the central projections of the cochlear nerve in the hamster revealed by the fluorescent tracer DiI.

A new fluorescent tracer, DiI, may be used postmortem in perfused animals making placement in small structures such as the cochlea much less difficult. We have mapped cochlear nerve terminations in the cochlear nucleus with DiI and, using three-dimensional reconstructions, have demonstrated the topography and geometry of the cochlear input. By placing DiI in two regions of the cochlea, we have demonstrated that terminations from the cochlea form stacked sheets of inputs. If enough closely situated ganglion cells were labeled in the cochlea, a well-delineated stripe of label could be found in each section of the cochlear nucleus up to the superficial granule cell region. Here a small extension of label, separate from the stripe may represent the medial olivocochlear axons. When fewer axons were labelled in the cochlear nerve, the sheets were absent and discontinuous patches of label were found. These patches apposed rostrocaudally to form bands of label that run orthogonal to the tonotopic organization.

Animals↗
PubMed1987

Morphology of labeled afferent fibers in the guinea pig cochlea.

Cochlear afferent and efferent fibers in the guinea pig were labeled by focal extracellular injections of horseradish peroxidase into the spiral ganglion of the basal turn. The morphology and pattern of termination of these fibers were studied by light microscopy. Fibers labeled by injections into the peripheral side of the ganglion could be grouped on the basis of their courses and terminations in the cochlea into two classes of afferent fibers, two classes of efferent (olivocochlear) fibers, and other presumably autonomic fibers. This paper describes the characteristics of labeled afferent fibers and their parent ganglion cells. Peripheral afferent fibers were grouped into two major classes: thick (mean diameter 1.7 micron) radial fibers projecting in a primarily radial fashion from the spiral ganglion and terminating on single inner hair cells and thin (mean diameter 0.5 micron) outer spiral fibers that spiral basalward in the organ of Corti to terminate on outer hair cells, usually in one row. For outer spiral fibers, the number of outer hair cells contacted and the length of the terminal region depend on the row of outer hair cells contacted, with third-row fibers forming, on the average, the most extensive region of termination. Within the spiral ganglion, two types of ganglion cells could be distinguished: type-I ganglion cells of large size (mean soma area = 216 microns 2) with a ratio of central process diameter to peripheral process diameter greater than one and type-II ganglion cells of smaller size (mean soma area = 100 microns 2) and a central to peripheral process ratio near one. In three cochleae in which injections were made central to the ganglion, 11 type-I ganglion cells have been traced to radial fibers contacting inner hair cells and eight type-II ganglion cells have been traced to outer spiral fibers contacting outer hair cells. Thus the afferent innervation of the guinea pig cochlea is similar to the pattern described in other mammals, in which there is separate innervation of the inner and outer hair cells by the two types of ganglion cells. The central axons of both types of ganglion cells were traced individually through serial sections of a block of tissue containing the cochlea, the auditory nerve, and the cochlear nucleus. They followed similar courses in the auditory nerve, and the axons followed into the cochlear nucleus bifurcated in similar regions of the interstitial portion.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1992

Tonotopic Order in the Adult and Developing Auditory System of the Rat as Shown by c-fos Immunocytochemistry.

Immediate early genes such as the proto-oncogene c-fos can be expressed in neurons following synaptic excitation by sensory stimulation. C-fos immunocytochemistry has subsequently been shown to be a very sensitive marking technique for neuronal activity. Here, antibodies against the c-fos protein product Fos were used to map the tonotopic organization in the auditory system of adult and developing rats. After stimulating adult rats with pure-tone pulses, bands of Fos-immunoreactive neurons revealed the frequency representation in seven brainstem nuclei: all three subdivisions of the cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the ventral nucleus of the trapezoid body, the rostral periolivary nucleus, the dorsal nucleus of the lateral lemniscus and the inferior colliculus. With the exception of the dorsal cochlear nucleus and the inferior colliculus, tonotopicity has not been previously demonstrated in the brainstem nuclei of the rat. During development two striking results were obtained. First, beginning at postnatal day 14 (i.e. approximately 2 days after physiological hearing begins in rats), not only low but also high frequencies were able to induce strong Fos immunoreactivity, indicating that gradual recruitment of formerly unresponsive high-frequency sites does not occur in the rat. Second, a gradual age-related shift of the position of isofrequency bands was not seen in any of the nuclei, suggesting that changes in frequency - place code do not occur after 2 weeks postnatally. These results indicate that the rat's auditory brainstem nuclei achieve their adult-like tonotopic organization early on, implying a somewhat different developmental time course than is found in other mammalian species.

Journal Article↗