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PubMed2004

Quantitative study of degeneration and new growth of axons and synaptic endings in the chinchilla cochlear nucleus after acoustic overstimulation.

To determine if acoustic overstimulation altered synaptic connections in the cochlear nucleus, anesthetized adult chinchillas, with one ear protected by a silicone plug, were exposed for 3 hr to a 108-dB octave-band noise, centered at 4 kHz, and allowed to survive for periods up to 32 weeks. This exposure led to cochlear damage in the unprotected ear, mainly in the basal regions of the organ of Corti. The anterior part of the ipsilateral posteroventral cochlear nucleus consistently contained a band of degenerating axons and terminals, in which electron microscopic analysis revealed substantial losses of axons and synaptic terminals with excitatory and inhibitory cytology. The losses were significant after 1 week's survival and progressed for 16-24 weeks after exposure. By 24-32 weeks, a new growth of these structures produced a resurgence in the number of axons and terminals. The net number of excitatory endings fully recovered, but the quantity with inhibitory cytology was only partially recouped. Neuronal somata lost both excitatory and inhibitory endings at first and later recovered a full complement of excitatory but not inhibitory terminals. Dendrites suffered a net loss of both excitatory and inhibitory endings. Excitatory and inhibitory terminals with unidentified postsynaptic targets in the neuropil declined, then increased in number, with excitatory terminals exhibiting a greater recovery. These findings are consistent with a loss and regrowth of synaptic endings and with a reorganization of synaptic connections that favors excitation.

Acoustic Stimulation↗
PubMed1994

Encoding of amplitude modulation in the cochlear nucleus of the cat.

1. Amplitude modulation (AM) is a pervasive property of acoustic communication systems. In the present study we investigate neural temporal mechanisms in the auditory nerve and cochlear nuclei of the pentobarbital sodium-anesthesized cat associated with the neural coding of 100% AM tones, both in quiet and in the presence of wideband, quasi-flat-spectrum noise. The AM carrier frequency was set to the neuron's characteristic frequency (CF) and the sound pressure level (SPL) of acoustic stimuli was varied over a wide dynamic range of intensities (< or = 40 dB). The temporal AM-encoding capability of auditory neurons was measured by computing the synchronization coefficient (SC) of the neural response to the signal's modulation and carrier frequency. The temporal modulation transfer function (tMTF) of a neuron was then computed by measuring the SC of the response to signals of variable fmod (50-2550 Hz). 2. Neurons in the cochlear nuclei synchronize on average more highly to the modulation frequency than fibers of comparable CF, threshold, and spontaneous rate in the auditory nerve. The disparity in performance is greatest at high SPLs and low signal-to-noise ratios. However, there is a significant degree of diversity in AM-encoding capability among neurons in both the cochlear nuclei and auditory nerve. Among auditory nerve fibers (ANFs), low- and medium-spontaneous-rate (SR) units (SR < 18 spike/s) phase-lock with greater precision than comparable high-SR units at any given frequency, particularly at moderate to high SPLs, consistent with previous studies. 3. The phase-locking capabilities of neurons in the cochlear nucleus are considerably more variable than in the auditory nerve. Moreover, the variability itself depends on two distinct measures of phase-locking performance. Most ANFs are capable of phase-locking to frequencies as high as 3-4 kHz. In the cochlear nucleus many unit types do not phase-lock to modulation frequencies > 1 kHz. As a result, phase-locking performance is measured on the basis of two parameters, maximum synchronization, irrespective of stimulus frequency, and the upper frequency limit for significant phase-locking. 4. Cochlear nucleus neurons may be divided into three distinct groups on the basis of maximum synchronization capability. In group 1 are the primary-like (PL) units of the anteroventral division, whose phase-locking capabilities are comparable with those of high-SR ANFs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: a kainic acid lesion study in guinea pigs.

The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(2)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the posteroventral cochlear nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons.

Acoustic Stimulation↗
PubMed1991

Comparison of the auditory sensitivity of neurons in the cochlear nucleus and inferior colliculus of young and aging C57BL/6J and CBA/J mice.

Thresholds of neurons to sounds were compared as a function of central auditory structure [ventral cochlear nucleus (VCN), dorsal cochlear nucleus (DCN), and inferior colliculus (IC)] in young and middle-aged C57BL/6J mice (multiple- and single-unit recordings) and in young and old CBA/J mice (single-unit recordings). Middle-aged C57 mice show progressive loss of sensitivity to high frequencies and noise due to cochlear pathology; CBA mice show little loss of sensitivity through most of their lifespan. Multiple-unit threshold curves (MTCs) for tones indicated that neurons in the C57 VCN suffered a greater degree of age-related loss of sensitivity than neurons in the IC (from an earlier study). Furthermore, whereas the low frequency portions of MTCs in IC neurons in high frequency tonotopic regions typically become 'sensitized' in middle-aged C57 mice (i.e., lower thresholds than young mice), such was not the case for VCN neurons. In contrast to VCN neurons, MTCs of the population of DCN neurons studied were statistically indistinguishable from those of the IC. Measurements of single-unit response areas in C57 mice corroborated the MTCs. In CBA mice, little effect of age was found in comparing single-unit response areas of young and old mice. The findings indicate that sensorineural impairment in middle-aged C57 mice is accompanied by threshold changes that are more severe in the VCN than in the IC or DCN. Because the VCN and DCN are believed to play different roles in hearing, the functions they support should, likewise, be affected to different extents by age-related hearing loss.

Acoustic Stimulation↗
PubMed1990

Evoked vertex and inferior colliculus responses to electrical stimulation of the cochlear nucleus.

Evoked potentials were recorded from the vertex and the inferior colliculus in guinea pigs in response to electrical stimulation of the cochlear nucleus complex. The stimuli consisted of 80-microseconds biphasic pulses, ranging from 20 to 5,000 microA. The effect of electrode location (nerve root area, surface, and in-depth dorsal cochlear nucleus) on the evoked response was assessed by measuring amplitudes, latencies, and thresholds as a function of stimulating current levels. Stimulation of the nerve root area resulted in the shortest latencies, the largest amplitudes, and the lowest thresholds, whereas the surface of the dorsal cochlear nucleus was the least effective stimulating site.

Amplifiers, Electronic↗
PubMed1990

Morphology and physiology of cells in slice preparations of the posteroventral cochlear nucleus of mice.

In an effort to understand what integrative tasks are performed in the cochlear nuclei, the present study was undertaken to describe neuronal circuits in the posteroventral cochlear nucleus (PVCN) anatomically and physiologically. The cochlear nuclear complex receives auditory information from the cochlea through the auditory nerve. Within the cochlear nuclei, signals travel along several parallel and interconnected pathways. From the cochlear nuclei, transformed versions of the signals are passed to higher auditory centers in the brainstem. We have recorded electrophysiological responses from cells that were subsequently visualized with horseradish peroxidase (HRP). Responses to shocks to the auditory nerve root and to intracellularly injected current pulses were recorded and correlated with morphology. Two types of stellate cells and octopus cells were distinguished. T stellate cells project out of the cochlear nuclei through the Trapezoid body; D stellate cells do not. The axons of D stellate cells extend Dorsalward to the dorsal cochlear nucleus (DCN) but have not been traced out of the nucleus. Both T and D stellate cells have terminal collaterals in the multipolar cell region of the PVCN and in the DCN. The endings of one T stellate cell formed a narrow band rostrocaudally in the fusiform cell layer of the DCN that resembled an isofrequency band. The endings of one D stellate cell lay closely apposed to multipolar cells in the deep layer of the DCN. The dendrites of T stellate cells are often aligned along the path of auditory nerve fibers and end in tufts, whereas those of D stellate cells extend radially in the plane of the lateral surface of the PVCN toward granule cell areas and branch sparingly. Octopus cells have dendrites oriented perpendicularly to the path of auditory nerve fibers. Their axons were cut medially in the slices; none had collateral branches. Both T and D stellate cells were monosynaptically excited to threshold by shocks to the nerve root, indicating that they could participate in local circuits that we measure physiologically. T stellate cells have action potentials that peak at about 0 mV and are followed by single undershoots. The D stellate cell that was best impaled fired overshooting action potentials that were followed by double undershoots. Octopus cells were monosynaptically excited to threshold by shocks to the auditory nerve.

Action Potentials↗
PubMed2003

Axonal pathways to the lateral superior olive labeled with biotinylated dextran amine injections in the dorsal cochlear nucleus of rats.

The lateral superior olive (LSO) contains cells that are sensitive to intensity differences between the two ears, a feature used by the brain to localize sounds in space. This report describes a source of input to the LSO that complements bushy cell projections from the ventral cochlear nucleus (VCN). Injections of biotinylated dextran amine (BDA) into the dorsal cochlear nucleus (DCN) of the rat label axons and swellings in several brainstem structures, including the ipsilateral LSO. Labeling in the ipsilateral LSO was confined to a thin band that extended throughout the length of the structure such that it resembled an LSO isofrequency lamina. The source of this labeled pathway was not obvious, because DCN neurons do not project to the LSO, and VCN bushy cells were not filled by these injections. Filled neurons in several brainstem structures emerged as possible sources. Three observations suggest that most of the axonal labeling in the LSO derives from a single source. First, the number of labeled VCN planar multipolar cells and the amount of labeling in the LSO were consistent and robust across animals. In contrast, the number of labeled cells in most other structures was small and highly variable. Second, the locations of planar cells and filled axons in the LSO were related topographically to the position of the DCN injection site. Third, labeled terminal arborizations in the LSO arose from collaterals of axons in the trapezoid body (output tract of planar cells). We infer that planar multipolar cells, in addition to bushy cells, are a source of ascending input from the cochlear nucleus to the LSO.

Animals↗
PubMed1990

Auditory brainstem of the ferret: bilateral cochlear lesions in infancy do not affect the number of neurons projecting from the cochlear nucleus to the inferior colliculus.

Unilateral cochlear removal in infancy produces a number of changes in the structure and physiology of the central auditory system. To test the role that interaural competition plays in this plasticity, ferrets were reared with bilateral cochlear removals from the fourth postnatal week; before the time of the normal onset of auditory function. The totality of the removals was confirmed using brainstem response audiometry and cochlear histology. Following 3-month survival, the animals were injected with wheatgerm horseradish peroxidase in the left inferior colliculus. Retrogradely labeled neurons in the cochlear nucleus on each side were counted. Neither the absolute number nor the bilateral symmetry of the labeled neurons differed significantly from normal adult ferrets. Thus, bilateral cochlear removal does not produce the same change in brainstem connections as unilateral removal or unilateral conductive hearing loss. The results are consistent with the competitive hypothesis.

Animals↗
PubMed1984

Segregation of stimulus phase and intensity coding in the cochlear nucleus of the barn owl.

The cochlear nucleus of the barn owl is composed of two anatomically distinct subnuclei, n. magnocellularis (the magnocellular nucleus) and n. angularis (the angular nucleus). In the magnocellular nucleus, neurons tend to respond at a particular phase of a stimulus sine wave. Phase locking was observed for frequencies up to 9.0 kHz. The intensity-spike count functions of magnocellular units are characterized by high rates of spontaneous activity, a narrow range of intensities over which spike counts changed from spontaneous to saturation levels, and a small increase in spike counts with intensity over that range. In the angular nucleus, neurons showed little or no tendency to respond at a certain sinusoidal phase, although some showed weak phase locking for frequencies below 3.5 kHz. Angular units typically had low spontaneous rates, large dynamic ranges, and large increases in spike counts with intensity, resulting in high saturation levels. The clear difference between the two nuclei in sensitivity to both phase and intensity and the reciprocity in response properties support the hypothesis that each nucleus is specialized to process one parameter (phase or intensity) and not the other.

Animals↗
PubMed1999

Intracellular responses of onset chopper neurons in the ventral cochlear nucleus to tones: evidence for dual-component processing.

Intracellular responses of onset chopper neurons in the ventral cochlear nucleus to tones: evidence for dual-component processing. The ventral cochlear nucleus (VCN) contains a heterogeneous collection of cell types reflecting the multiple processing tasks undertaken by this nucleus. This in vivo study in the rat used intracellular recordings and dye filling to examine membrane potential changes and firing characteristics of onset chopper (OC) neurons to acoustic stimulation (50 ms pure tones, 5 ms r/f time). Stable impalements were made from 15 OC neurons, 7 identified as multipolar cells. Neurons responded to characteristic frequency (CF) tones with sustained depolarization below spike threshold. With increasing stimulus intensity, the depolarization during the initial 10 ms of the response became peaked, and with further increases in intensity the peak became narrower. Onset spikes were generated during this initial depolarization. Tones presented below CF resulted in a broadening of this initial depolarizing component with high stimulus intensities required to initiate onset spikes. This initial component was followed by a sustained depolarizing component lasting until stimulus cessation. The amplitude of the sustained depolarizing component was greatest when frequencies were presented at high intensities below CF resulting in increased action potential firing during this period when compared with comparable high intensities at CF. During the presentation of tones at or above the high-frequency edge of a cell's response area, hyperpolarization was evident during the sustained component. The presence of hyperpolarization and the differences seen in the level of sustained depolarization during CF and off CF tones suggests that changes in membrane responsiveness between the initial and sustained components may be attributed to polysynaptic inhibitory mechanisms. The dual-component processing resulting from convergent auditory nerve excitation and polysynaptic inhibition enables OC neurons to respond in a unique fashion to intensity and frequency features contained within an acoustic stimulus.

Acoustic Stimulation↗
PubMed2001

Origins of projections from the inferior colliculus to the cochlear nucleus in guinea pigs.

We used retrograde tracing techniques to examine the projections from the inferior colliculus to the cochlear nucleus in guinea pigs. Following injection of a retrograde tracer into one cochlear nucleus, labeled cells were found bilaterally in all subdivisions of the inferior colliculus. The majority of cells were located in the central nucleus and external cortex; relatively few cells were located in the dorsal cortex. Multipolar (stellate) cells were labeled in all subdivisions of the inferior colliculus. In the central nucleus, disk-shaped cells were also labeled. To determine whether individual collicular neurons send collateral projections to the cochlear nuclei on both sides, we injected different fluorescent tracers into left and right cochlear nuclei in the same animal. The inferior colliculi contained very few double-labeled cells, indicating that the projections to ipsilateral and contralateral cochlear nuclei originate from separate populations of cells.

Animals↗
PubMed1985

Electrical stimulation of cochlear nucleus in man.

Auditory percepts can be produced by electrical stimulation of the cochlear nucleus in man. The ability to locate accurately and stimulate selectively the cochlear nucleus after removal of an acoustic schwannoma was confirmed in this patient. The surgical approach, electrode design, and a discussion of the results and concerns of electrical stimulation are reviewed.

Auditory Perception↗
PubMed2004

Localization of the GABAB receptor 1a/b subunit relative to glutamatergic synapses in the dorsal cochlear nucleus of the rat.

Metabotropic gamma-aminobutyric acid receptors (GABA(B)) are involved in pre- and postsynaptic inhibitory effects upon auditory neurons and have been implicated in different aspects of acoustic information processing. To understand better the mechanisms by which GABA(B) receptors mediate their inhibitory effects, we used pre-embedding immunocytochemical techniques combined with quantification of immunogold particles to reveal the precise subcellular distribution of the GABA(B1) subunit in the rat dorsal cochlear nucleus. At the light microscopic level, GABA(B1) was detected in all divisions of the cochlear complex. The most intense immunoreactivity for GABA(B1) was found in the dorsal cochlear nucleus, whereas immunoreactivity in the anteroventral and posteroventral cochlear nuclei was very low. In the dorsal cochlear nucleus, a punctate labeling was observed in the superficial (molecular and fusiform cell) layers. At the electron microscopic level, GABA(B1) was found at both post- and presynaptic locations. Postsynaptically, GABA(B1) was localized mainly in the dendritic spines of presumed fusiform cells. Quantitative immunogold immunocytochemistry revealed that the highest concentration of GABA(B1) in the plasma membrane was in dendritic spines, followed by dendritic shafts and somata. Thus, the most intense immunoreactivity for GABA(B1) was observed in dendritic spines with a high density of immunogold particles at extrasynaptic sites, peaking around 300 nm from glutamatergic synapses. This is in contrast to GABAergic synapses, in which GABA(B1) was only occasionally found. Presynaptically, receptor immunoreactivity was detected primarily in axospinous endings, probably from granule cells, in both the active zone and extrasynaptic sites. The localization of GABA(B1) relative to synaptic sites in the DCN suggests a role for the receptor in the regulation of dendritic excitability and excitatory inputs.

Animals↗
PubMed2006

Deafness associated changes in expression of two-pore domain potassium channels in the rat cochlear nucleus.

Two-pore domain potassium channels (K(2PD)+) play an important role in setting resting membrane potential by regulating background leakage of potassium ions, which in turn controls neuronal excitability. To determine whether these channels contribute to activity-dependent plasticity following deafness, we used quantitative real-time PCR to examine the expression of 10 K(2PD)+ subunits in the rat cochlear nucleus at 3 days, 3 weeks and 3 months after bilateral cochlear ablation. There was a large sustained decrease in the expression of TASK-5, a subunit that is predominantly expressed in auditory brain stem neurons, and in the TASK-1 subunit which is highly expressed in several types of cochlear nucleus neurons. TWIK-1 and THIK-2 also showed significant decreases in expression that were maintained across all time points. TWIK-2, TREK-1 and TREK-2 showed no significant change in expression at 3 days but showed large decreases at 3 weeks and 3 months following deafness. TRAAK and TASK-3 subunits showed significant decreases at 3 days and 3 weeks following deafness, but these differences were no longer significant at 3 months. Dramatic changes in expression of K(2PD)+ subunits suggest these channels may play a role in deafness-associated changes in the excitability of cochlear nucleus neurons.

Animals↗