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PubMed1999

Characterization of tuberculo-ventral neurons in the dorsal cochlear nucleus of the guinea pig.

Tuberculo-ventral neurons in the deep polymorphic layer of the dorsal cochlear nucleus of the guinea pig are immunopositive to glycine, their main neurotransmitter, as revealed by post-embedding immunogold. The initial size of gold particles (10-20 nm) was increased (40-70 nm) by silver intensification for a better and rapid individuation of glycine positive cells at low magnification. The most specific ultrastructural characteristic of tuberculo-ventral neurons is their synaptic profile that shows most flat-pleomorphic axo-somatic boutons. This synaptic profile is different from that of other medium size neurons, such as cartwheel neurons in the superficial layer of the dorsal cochlear nucleus. The synaptic profile of tuberculo-ventral neurons together with other characteristics may explain their activity connected to the neural network responsible for echos suppression or/and sound localization.

Animals↗
PubMed2003

Ultrastructural distribution of glycinergic and GABAergic neurons and axon terminals in the rat dorsal cochlear nucleus, with emphasis on granule cell areas.

A knowledge of neurotransmitters in the neurons of the rat cochlear nuclear complex is of importance in understanding the function of auditory circuits. Using post-embedding ultrastructural immunogold labelling, the distribution of glycinergic and GABAergic neurons and axonal terminals has been studied in the molecular, fusiform and polymorphic layers of the rat dorsal cochlear nucleus (DCN). This technique is not limited by the penetration of antibodies into the nervous tissue as in pre-embedding methods, and allows a fine neurochemical mapping of the nervous tissue. Numerous glycinergic and GABAergic axon terminals contain pleomorphic and flat synaptic vesicles, and are present in all layers (1, 2, 3) of the dorsal cochlear nucleus. Glycine and GABA-negative large terminals (mossy fibres) are mainly seen in granule cell areas of layer 2 (fusiform layer). Mossy fibres contact the dendrites of GABA- and glycine-negative granule cells and of the few unipolar brush cells (excitatory neurons). The least common cells in the granule cell areas are GABAergic and glycinergic Golgi-stellate neurons. In unipolar brush cells, aggregations of vesicles seem to be the origin of their characteristic ringlet-bodies. Golgi-stellate cells send their inhibitory terminals to the dendrites of granule and unipolar brush cells, occasionally directly to mossy fibres. Small or (less frequently) large GABAergic terminals contact the soma or the main dendrite of unipolar brush cells. The circuit of a hypothetical functional unit of neurons in the DCN is proposed. The inputs from auditory tonotopic or non-auditory non-tonotopic mossy fibres eventually reach pyramidal cells through axons from the granule cells or unipolar brush cells. Pyramidal cells convey an excitatory signal from the DCN to higher mesencephalic nuclei for further elaboration of the acoustic signal.

Animals↗
PubMed1976

Role of centrifugal pathways to cochlear nucleus in determination of critical bandwidth.

Atropine sulfate was applied locally to the cochlear nucleus of three unanesthetized cats in order to block the cholinergic centrifugal innervation of the nucleus. The critical bandwidth was measured behaviorally from the masked thresholds of 1-kHz tone pips in different bandwidths of masking noise. Atropine increased the critical bandwidth markedly. This suggests that normally the centrifugal pathways influence the critical bandwidth. Saline solutions alone had no effect, and if the cannula was not accurately implanted over the cochlear nucleus, atropine had no effect either.

Acoustic Stimulation↗
PubMed1976

Synaptic events and discharge patterns of cochlear nucleus cells. I. Steady-frequency tone bursts.

Unitary discharge patterns (peristimulus time histograms or PSTH) and synaptic events were studies with intracellular recording techniques in 164 cat cochlear nucleus cells to steady-frequency tone bursts 250 ms in duration. There were four response types defined on the basis of the shape of the discharge patterns to tones at the characteristic or best frequency. Primarylike units resemble eighth nerve fibres and have a maximum discharge at tone onset, followed by a smooth decline to a steady level of activity. Buildup units have a transient response at tone onset, followed a period of little or not activity before gradually increasing their discharge rate for the remainder of the tone burst. Onset units have an initial burst of spikes at the onset, with little or no activity for the remainder of the tone burst. Pause units have a long latency (10-30 ms) between tone onset and the appearance of low levels of unit activity, which then gradually increase in rate for the remainder of the tone burst. Changes in signal frequency or intensity within the excitatory response area did not modify response patterns of primarylike and onset units, but could evoke primarylike patterns in buildup and pause units. Inhibition manifested by suppression of spontaneous activity and membrane hyperpolarization were of three kinds: 1) in response to signals at the edges of the excitatory response area (i.e., the inhibitory surround) and detected in onset buildup, and pause units but not in primarylike units; 2) occurring at the offset of tones in the excitatory response area and detected in all four types of cochlear nucleus cells; 3) during excitatory tone bursts in onset and buildup units associated with the periods of suppressed unit activity. Membrane hyperpolarization did not accompany the delay in unit activity after tone onset in pause units. Inhibitory events in cochlear nucleus cells provide mechanisms for producing diversity in the temporal pattern of discharges to acoustic signals which may underly the encoding of complex features of sounds.

Acoustic Stimulation↗
PubMed1994

Internally-generated sound stimulates cochlear nucleus units.

The body generates many physiological sounds. One of the most prominent is that produced by the blood flowing inside the vessels with each heart beat. On the other hand, the cochlea is a very sensitive receptor with a low threshold. Given the anatomical close proximity of the carotid artery and other vessels to the inner ear, the possibility of its being stimulated is very high. Cochlear nucleus spontaneous as well sound-responding auditory units were studied. A close relationship between the heart beat, that is the blood flow, and the cochlear nucleus firing was demonstrated, in anesthetized and awake guinea-pigs. Temporary mechanical interruption of the blood flow through the ipsilateral carotid artery abolished firing increments at the cochlear nucleus time-locked to the heart beat. We conclude that one component of the so called 'spontaneous' firing in the auditory system is actually evoked activity due to normal body-generated sounds or noises.

Acoustic Stimulation↗
PubMed2003

Pontine sources of norepinephrine in the cat cochlear nucleus.

In the current study, the distribution of noradrenergic neurons in the pontine tegmentum that project to the cochlear nucleus was determined with retrograde tract tracing combined with neurotransmitter immunohistochemistry in the cat. Double-labeled neurons were observed in all noradrenergic cell groups, in both the dorsolateral and the ventrolateral tegmentum. Half of the double-labeled cells were located in the locus coeruleus complex. Most of these were situated in its ventral division. Most other double-labeled cells were located in peribrachial regions, especially lateral to the brachium conjunctivum. Relatively few double-labeled cells were observed in both the A4 and the A5 cell groups, 2% and 0.4%, respectively, of the total. Except for neurons in A5, which projected only contralaterally, the projections were bilateral, with an ipsilateral preponderance. The results indicate that neurons located in the ipsilateral dorsolateral tegmentum, namely, in the locus coeruleus complex and the peribrachial region, are the primary source of pontine noradrenergic afferents to the cochlear nucleus of the cat.

Adrenergic Fibers↗
PubMed2006

Origin of hyperactivity in the hamster dorsal cochlear nucleus following intense sound exposure.

This study sought to determine whether maintenance of noise-induced dorsal cochlear nucleus (DCN) hyperactivity depends on descending projections. Twenty-two hamsters were exposed under anesthesia to a 10-kHz tone at 125-130 dB SPL for 4 hr, and another 21 unexposed animals served as controls. After approximately 4-6 weeks of recovery, surgical transections were made to isolate the DCN from its adjacent brainstem structures. Spontaneous multiunit activity was recorded from the DCN surface 30-40 min after the surgical manipulations. Spontaneous rates were derived from the recording sites of the DCN along its mediolateral axis for each animal, yielding average spontaneous rates for both control and exposed groups. Histology was performed to assess the degree of sectioning of descending fiber tract connections to the cochlear nucleus, via the acoustic striae route, subpeduncular route, trapezoid body route, and ventral route of the olivocochlear bundle connection. The results showed that complete or nearly complete transections of descending inputs did not affect significantly the magnitude of DCN hyperactivity. However, this manipulation triggered a lateral shift of the peak mean rate, suggesting that descending inputs may play a modulatory role on the profile of DCN hyperactivity. Indeed, exposed animals with transection of only the strial route of entry manifested a level of hyperactivity much higher than that observed in exposed animals in which no sections were performed. This enhancement of DCN hyperactivity was weakened by damage to the subpeduncular or trapezoid routes of input, suggesting that the dorsally located inputs may have an inhibitory effect on DCN hyperactivity.

Acoustic Stimulation↗
PubMed2006

Projections from auditory cortex to cochlear nucleus: A comparative analysis of rat and mouse.

Mammalian hearing is a complex special sense that involves detection, localization, and identification of the auditory stimulus. The cerebral cortex may subserve higher auditory processes by providing direct modulatory cortical projections to the auditory brainstem. To support the hypothesis that corticofugal projections are a conserved feature in the mammalian brain, this article reviews features of the rat corticofugal pathway and presents new data supporting the presence of similar projections in the mouse. The mouse auditory cortex was localized with electrophysiological recording and neuronal tracers were injected into AI. The cochlear nucleus was dissected and examined for terminal fibers by light and electron microscopy. Bouton endings were found bilaterally forming synapses with dendrites of granule cells of the cochlear nucleus. This report provides evidence for direct auditory cortex projections to the cochlear nucleus in the mouse. The distribution of projections to the granule cell domain and the synapses onto granule cell dendrites are consistent with what has been reported for rats and guinea pigs. These findings suggest a general plan for corticofugal modulation of ascending auditory information in mammals. Corticobulbar inputs to the auditory brainstem likely provided a survival advantage by improving sound detection and identification, thus allowing the development of complex social behaviors and the navigation of varied environments.

Animals↗
PubMedDate not supplied

Cisplatin-induced increases in spontaneous neural activity in the dorsal cochlear nucleus and associated outer hair cell loss.

Tinnitus is one of the consequences of cisplatin chemotherapy, but its underlying mechanisms are not well understood. Since it has been shown that cisplatin causes outer hair cell loss, it is possible that loss of these cells might induce tinnitus by increasing spontaneous activity in the central auditory system. To test this possibility, the present study examined the effects of cisplatin treatment on cochlear hair cells and on spontaneous neural activity in the dorsal cochlear nucleus of hamsters. Recordings, carried out approximately 1 month after cisplatin treatment, demonstrated significant increases in spontaneous activity across broad regions of the dorsal cochlear nucleus relative to levels in saline-treated controls. Histological results showed that cisplatin-treated animals also displayed dramatic loss of outer hair cells over most of the basal turn of the cochlea. Inner hair cells remained intact, although some evidence of damage to their stereocilia was evident. These findings indicate that cisplatin treatment causes abnormalities in spontaneous activity in the dorsal cochlear nucleus that are associated with widespread damage to outer hair cells. However, since some damage to inner hair cells was also observed, the role of inner hair cell injury in contributing to higher spontaneous activity cannot be ruled out.

Animals↗
PubMedDate not supplied

Immunocytochemistry of glycine in small neurons of the granule cell areas of the guinea pig dorsal cochlear nucleus: a post-embedding ultrastructural study.

The axon terminals of the acoustic nerve contact different part of the cochlear nucleus including granule cell areas. Little is known of the cell composition and neural circuits of granule cell areas present in the fusiform and upper polymorphic layers of the dorsal cochlear nucleus in the guinea pig. The present ultrastructural immunocytochemical study exploits the technique of post-embedding immunogold and silver intensification to reveal the characteristics of small neurons in granule cell areas. Few neurons (Golgi-stellate cells) use glycine as inhibitory neurotransmitter which is present in symmetric synaptic boutons with pleomorphic and flat vesicles. In contrast, most neurons (granule and unipolar brush cells) are not glycine-positive, and presumably not excitatory. Most of the large axons (mossy fibres) in granule areas are probably excitatory (glycine-negative and storing round synaptic vesicles) and contact unipolar brush cells forming large synapses or granule cell dendrites by small synapses. A few large glycinergic boutons (inhibitory) also contact unipolar brush cells. The excitatory circuit of mossy fibre-unipolar brush and granule cells may be inhibited by the glycinergic terminals from the few glycinergic cells (Golgi-stellate neurons) present within the granule cell areas. The latter are not contacted by large mossy-like glycine terminals.

Animals↗
PubMedDate not supplied

Neurotransmitters of the cochlea and cochlear nucleus: immunocytochemical evidence.

Many neurotransmitter candidates have been identified in the cochlea and cochlear nucleus with the use of immunocytochemical techniques. Choline acetyltransferase immunoreactivity suggests acetylcholine as a transmitter of medial and lateral efferent systems in the cochlea. Immunoreactivities to enkephalins, dynorphins, calcitonin gene-related peptide, and tyrosine hydroxylase (a marker for dopamine) are also found in lateral efferents. Choline acetyltransferase, enkephalin, and dynorphin immunoreactivities are co-contained in neurons of the lateral system. In the anteroventral cochlear nucleus, the inhibitory amino acid transmitters, gamma aminobutyric acid (GABA), and glycine, as well as the presumed excitatory amino acid transmitter of the auditory nerve, have been directly or indirectly localized, immunocytochemically, to discrete populations of terminals on spherical cells with distinct morphologic characteristics.

Acetylcholine↗
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↗
PubMed1978

Functional characteristics of cochlear nucleus in behaving cat examined by acoustic masking of electrical stimuli.

1. Cats were trained, using an operant procedure, to detect and respond to electrical stimulation delivered in the vicinity of the cochlear nucleus. The electrical stimuli were presented both in silence and in synchrony with repeated noise bursts to determine whether detection thresholds for the electrical stimuli were elevated by the acoustic masking noise. 2. For stimulation sites centered within auditory structures (cochlear nucleus or acoustic nerve root), the acoustic maskers caused a consistent elevation of the electrical detection thresholds. For stimulation sites that were in or bordered on nonacoustic neural structures (e.g., vestibular), the acoustic maskers caused little or no elevation of electrical detection thresholds. 3. The magnitude of the acoustic masking effect was monotonically related to the intensity of the acoustic masker across the range of intensities tested. 4. The magnitude of the masking effect was strongly dependent on the relative timing of the stimulus pulse and the masker noise burst. Maximum masking occurred when the pulse just followed the onset of the neural activity in cochlear nucleus evoked by the masker burst. Less masking occurred when the electrical pulse occurred at the middle or end of the masker burst, and still less when the pulse occurred just prior to the onset (backward masking) or just after the offset (forward masking) of the masker burst. 5. The magnitude of the masking effect also depended on the frequency of the acoustic masker. For tone bursts, masking was maximal for each electrode at a particular frequency and declined monotonically for masker frequencies above or below the optimal frequency. 6. It is concluded that the masking of an electrical stimulus by an acoustic stimulus depends on a direct interaction between the neural responses evoked by the two stimuli, and that similar central, neural interactions may contribute to acoustic masking of acoustic stimuli. It is also concluded that the technique of masking an electrical stimulus by an acoustical stimulus is a precise and useful tool for the study of sensory-neural organization in intact behaving animals.

Animals↗
PubMed2003

Synaptic nests lack glutamate transporters in the cochlear nucleus of the mouse.

Synaptic nests are closely packed collections of synaptic endings. Nests may be deficient in the glial processes which usually separate terminals in the CNS and which transport much of the glutamate associated with high levels of excitatory activity. We hypothesized that nests might lack glial glutamate transporters, but possibly would conserve neuronal glutamate transporter. Although present throughout the brain, nests are especially numerous in the cochlear nucleus. We performed immunoelectron microscopy by preembedding peroxidase and immunogold methods and by postembedding immunogold to detect expression of the glutamate transporters GLAST, GLT-1, and EAAC1 in the mouse cochlear nucleus. Our results show that the glial transporters, GLAST and GLT-1, are absent in synaptic nests. This deficiency is not compensated by the neuronal transporter EAAC1, which is poorly represented in nests. Outside synaptic nests, all three glutamate transporters are strongly expressed in the cochlear nucleus. Thus, glutamate released outside nests should be quickly bound by transporters and removed from the extracellular glutamate pool. Glutamate released within synaptic nests may persist long enough to permit diffusion to extrajunctional targets in the nest, including presynaptic receptors. Consequently, synaptic nests may play a role in modulation of synaptic activity but also in excitotoxic mechanisms.

Amino Acid Transport System X-AG↗
PubMedDate not supplied

Peripheral cell loss related to calcium binding protein immunocytochemistry in the dorsal cochlear nucleus in CBA/CaJ mice during aging.

The influence of cochlear hair cell and spiral ganglia neuron loss on calcium binding protein immunoreactivity (calretinin, parvalbumin and calbindin) in the dorsal and posteroventral cochlear nuclei (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months) was determined. Since calcium binding proteins have buffering properties against calcium overload, they may have a protective role during aging. It is shown that the percentage of calretinin- and parvalbumin-immunopositive neurons in the DCN showed a statistically significant positive correlation with inner hair cell loss, outer hair cell loss, and spiral ganglion cell loss. A correlation was also found between aging and the auditory periphery, and calcium binding proteins in the DCN. These findings imply that the pathophysiological state of the auditory periphery may influence the neuronal homeostasis in the dorsal cochlear nucleus.

Aging↗
PubMed1994

Paired tone facilitation in dorsal cochlear nucleus neurons: a short-term potentiation model testable in vivo.

It has been suggested that the dorsal cochlear nucleus (DCN) is involved in coding stimulus history or prior auditory activity [Manis (1989) J. Neurophys., 61, 149-161; Manis (1990) J. Neurosci., 10, 2338-2351]. The major output neurons of the DCN are the fusiform (pyramidal) cells which are thought to receive excitatory inputs from the descending branch of the acoustic nerve onto their basal dendrites and significant inhibitory glycinergic and GABAergic inputs to the soma and dendrites. The apical dendrites of these neurons lie within the molecular layer of the DCN and encounter parallel fibers which are thought to utilize the excitatory amino acid neurotransmitter glutamate. In this study of anesthetized chinchillas, we found that, in contrast to the responses of acoustic nerve fibers and most cochlear nucleus neurons which are masked by an appropriate preceding signal, many DCN principal cells are facilitated during the second of two identical stimuli. Facilitated DCN responses often have a reduced interspike interval and a more chopper-like temporal response pattern to the second characteristic frequency tone. This paired tone facilitation in the chinchilla DCN provides as in vivo model of short-term potentiation elicited by sensory stimulation similar to the paired-pulse facilitation observed with electrical stimulation in other models.

Acoustic Stimulation↗
PubMed1994

Changes in the cat cochlear nucleus following neonatal deafening and chronic intracochlear electrical stimulation.

The effects of chronic intracochlear electrical stimulation on the cochlear nucleus (CN) were studied in eight cats that were neonatally deafened by daily intramuscular injections of neomycin. Profound hearing loss was confirmed in each animal by auditory brainstem response (ABR) and frequency following response (500 Hz) testing. Five of the kittens were implanted unilaterally with a scala tympani electrode array at ages 8-16 weeks. These kittens were stimulated daily for four hours at 2 dB above the evoked ABR threshold, over a period of three months, and subsequently euthanized for histological analysis at 26-32 weeks of age. The three remaining deaf kittens were maintained without stimulation over prolonged periods in order to study the long-term consequences of neonatal deafening, and were euthanized at 66-133 weeks of age. This study compares the CN of these deafened experimental animals and the CN of normal adult cats. Three experimental parameters were examined: CN volume, cross-sectional area of spherical cells in the rostral anteroventral cochlear nucleus (AVCN), and spherical cell density in this same region. The CN in animals that received electrical stimulation showed significant bilateral degenerative changes in all three measured parameters. Total nuclear volume was reduced by 35-36%, spherical cell size was reduced by 20-26%, and spherical cell density decreased by 36-42%, as compared to the normal cat CN. Comparisons were also made in the stimulated animals between CN ipsilateral to the stimulated cochlea and the contralateral, unstimulated CN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Gamma-D-glutamylaminomethyl sulfonic acid (GAMS) distinguishes subtypes of glutamate receptor in the chick cochlear nucleus (nuc. magnocellularis).

Because kainic acid (KA) is more potent than other excitatory amino acids (EAAs) in affecting synaptic transmission in the cochlear nucleus, previous reports have concluded that primary afferent neurotransmission to the cochlear nucleus in birds and mammals is mediated by KA-preferring non-N-methyl-D-aspartate (non-NMDA) EAA receptors. Since this conclusion is at odds with a number of studies suggesting that rapid excitatory neurotransmission in the CNS is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring non-NMDA receptors, we re-examined the pharmacology of synaptic transmission between the cochlear nerve and nucleus magnocellularis (NM) in chickens, using bath application of drugs and recording of field potentials evoked in NM by electrical stimulation of the cochlear nerve in vitro. A series of EAA agonists produced complete, concentration-dependent and reversible suppression of postsynaptic responses: the order of potency was domoic acid (DO) greater than KA greater than AMPA much greater than quisqualic acid much greater than L-glutamic acid (Glu). Three quinoxalinedione antagonists of non-6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione NMDA receptors also produced complete, concentration-dependent and reversible suppression of postsynaptic responses in NM without affecting the presynaptic action potential; the half-maximal inhibitory concentrations (IC50's) were 2.7 +/- 0.4 microM for 6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione (NBQX), 5.3 +/- 0.1 microM for 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 10.6 +/- 1.2 microM for 6,7-dinitroquinoxaline-2,3-dione (DNQX).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗