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PubMed1993

Discharge suppression in the silent interval preceding the tone burst in pause-build units of the dorsal cochlear nucleus of the unanesthetized decerebrate cat.

A recent intracellular study of dorsal cochlear nucleus (DCN) neurons in vitro by Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] suggests that the expression of the pause-build discharge pattern is in large part dependent on hyperpolarization of their membrane potentials in a period just preceding a depolarizing stimulus ("hyperpolarization conditioning" hypothesis). Our examination of the activity of a sample of pause-build units (n = 72) revealed suppression of discharge activity during a time window of the silent interstimulus interval (SII) just preceding the tone burst relative to the spontaneous rate in 74% of all units. The discharge suppression of a subset of DCN pause-build units in the SII satisfies a requirement of the "hyperpolarization conditioning" hypothesis, and thus supports the hypothesis.

Acoustic Stimulation↗
PubMed1998

Increases in spontaneous activity in the dorsal cochlear nucleus of the rat following exposure to high-intensity sound.

The effects of intense sound exposure on neural activity in the dorsal cochlear nucleus (DCN) were studied in the rat. Seventeen anesthetized adult rats were exposed to a 10-kHz tone at 125-130 dB SPL for 4 h. Fourteen unexposed rats served as controls. Spontaneous activity (SA) and neural thresholds at the characteristic frequency were measured in three rows of 8-12 sites along the mediolateral, tonotopic, axis of the DCN surface 27-61 days after exposure. The results showed that intense tone exposure induced chronic increases in SA. This hyperactivity was found to be distributed broadly across the DCN with an emphasis around the 10-kHz locus and was associated with shifted response thresholds. These findings demonstrate the usefulness of the rat for studies of physiological phenomena related to noise-induced tinnitus and hearing loss.

Animals↗
PubMed2004

Activity in the dorsal cochlear nucleus of hamsters previously tested for tinnitus following intense tone exposure.

Chronic increases in spontaneous multiunit activity can be induced in the dorsal cochlear nucleus (DCN) of hamsters by intense sound exposure (Kaltenbach and McCaslin, 1996). It has been hypothesized that this hyperactivity may represent a neural code that could underlie the sound percepts of tinnitus. The goal of the present study was to determine whether hyperactivity could be demonstrated in animals that had previously been tested for tinnitus, and, if so, whether animals differing in their behavioral evidence for tinnitus also differ in their levels of spontaneous activity. The results showed not only that levels of activity in exposed animals were higher than those in control animals, but the degree to which the activity was increased was related to the strength of the behavioral evidence for tinnitus. These findings are consistent with the hypothesis that hyperactivity in the DCN may be a physiological correlate of noise-induced tinnitus.

Acoustic Stimulation↗
PubMed1998

Mechanisms of the cochlear nucleus octopus cell's onset response: synaptic effectiveness and threshold.

Octopus cells are one of the principal cell types in the mammalian posteroventral cochlear nucleus. These cells respond to the onset of a toneburst with a precisely timed spike followed by little, if any, sustained activity. While experimental studies have partially characterized the cell, the mechanisms of this onset response are not well understood. The present study involved a model-based investigation that analyzed the responses of a compartmental model of the octopus cell in terms of synaptic effectiveness and dynamic spike threshold. The simulations demonstrate that properties of the onset response (first-spike latency, temporal precision of the first spike, and sustained firing rate) can be predicted from the values of these cell properties for a wide range of model configurations. These relationships were further analyzed through the development of mathematical expressions for synaptic effectiveness and dynamic spike threshold. This computational analysis resulted in a relatively simple explanation of the onset response, as well as predictions of the responses of octopus cells to nontonal, complex stimuli.

Auditory Perception↗
PubMed1998

Golgi cells in the superficial granule cell domain overlying the ventral cochlear nucleus: morphology and electrophysiology in slices.

Golgi cells are poised to integrate multimodal influences by participating in circuits involving granule cells in the cochlear nuclei. To understand their physiological role, intracellular recordings were made from anatomically identified Golgi cells in slices of the cochlear nuclei from mice. Cell bodies, dendrites, and terminals for all seven labeled cells were restricted to the narrow plane of the superficial granule cell domain over the ventral cochlear nucleus. The axonal arborization was the most striking feature of all Golgi cells; a dense plexus of terminals covered an area 200-400 microm in diameter in the vicinity of the cell body and dendrites. Axonal beads often surrounded granule cell bodies, indicating that granule cells are probable targets. Cells had input resistances up to 130 M omega and fired regular, overshooting action potentials. Golgi cells probably receive auditory nerve input, because shocks to the cut end of the auditory nerve excited Golgi cells with excitatory postsynaptic potentials (EPSPs). The latency of EPSPs shortened to a minimum and the amplitude of EPSPs grew in several steps as the strength of shocks was increased. The minimum latency of EPSPs in Golgi cells was on average 1.3 milliseconds, 0.6 milliseconds longer than the minimum latencies of EPSPs in nearby octopus and T stellate cells. The long latency raises the possibility that Golgi cells receive input from slowly conducting, unmyelinated auditory nerve fibers. Golgi cells are also excited by interneurons with N-methyl-D-aspartate receptors, probably granule cells, because repetitive shocks and single shocks in the absence of extracellular Mg2+ evoked late EPSPs that were reversibly blocked by DL-2-amino-5-phosphono-valeric acid.

Animals↗
PubMed2004

In vivo optical imaging of tone-evoked activity in the dorsal cochlear nucleus with a voltage sensitive dye.

We investigated the use of optical imaging for observing the spatial patterns of neural activation in the dorsal cochlear nucleus (DCN) of hamsters during tonal stimulation. The patterns of activation were studied in the DCN, in vivo, following application of a voltage sensitive dye, Di-2-ANEPEQ, to the DCN surface. Beginning 60-90 min following dye application, tones were presented to the ipsilateral ear. Electrophysiological recordings after dye application revealed no significant toxicity of Di-2-ANEPEQ that affected the frequency-tuning properties of DCN neurons. We examined areas of activation in response to each of a series of test stimuli consisting of pure tones ranging in frequency from 2 to 20 kHz. For each stimulus condition, images were collected over a stimulus interval of 400 msec and averaged over 32 stimulus repetitions. These images revealed areas of activation with definable epicenters. The epicenters shifted from lateral to more medial locations on the DCN surface with increases in stimulus frequency. Comparison with electrophysiological data indicated a close parallel between the tonotopic gradient defined by optical imaging and that defined by the distribution of characteristic frequencies. The principal temporal and spatial features of these optical responses are described.

Acoustic Stimulation↗
PubMed1995

A computer model of dorsal cochlear nucleus pyramidal cells: intrinsic membrane properties.

Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] studied "simple spiking," pyramidal cells of the dorsal cochlear nucleus (DCN) maintained in vitro. Response profiles to hyperpolarizing and depolarizing current pulses were generated. Hyperpolarization of the cell membrane followed by depolarization produced markedly different response profiles from those generated when no prehyperpolarization was imposed. By manipulating the magnitude of the hyperpolarizing and depolarizing pulses, "chopper," "pauser" and "build-up" response patterns, similar to those in vivo, could be generated by individual cells. Manis concluded that the different response profiles resulted from the modulation of intrinsic membrane conductances by the prehyperpolarizing pulses. Here a computer model is used to show that (a) steady-state hyperpolarization can influence cell responding to subsequent depolarization in a manner consistent with the data reported by Manis; and (b) the effects reported can be generated by the addition of a modeled transient potassium conductance to the standard Hodgkin-Huxley model of spike generation [A. L. Hodgkin and A. F. Huxley, J. Physiol. 117, 500-544 (1952)]. The model will be of use to those who wish to consider the role of various excitatory and inhibitory inputs to pyramidal cells and to establish their functional role within the DCN.

Cochlear Nucleus↗
PubMed1996

Effects of parallel fiber stimulation on neurons of rat dorsal cochlear nucleus.

We have compared the effects of parallel fiber stimuli on extracellularly recorded neurons showing regular or bursting spontaneous activity patterns in the dorsal cochlear nucleus of rat brainstem slices. Ninety percent of regular neurons failed to respond to stimulus currents (1.4 +/- 0.28 mA, mean +/- SEM) significantly greater than those (0.4 +/- 0.07 mA) that elicited responses from 96% of bursting neurons. Responses of bursting neurons were elicited from widely separated loci along the molecular layer. Kynurenic acid and CNQX or DNQX blocked both spontaneous firing and responses to parallel fiber stimuli of bursting neurons. The same agents also blocked responses of regular neurons but had little or no effect on their spontaneous firing rates. AP-5 caused small decreases in spontaneous rates of both bursting and regular neurons but did not appear to affect responses to stimuli. The data support the hypothesis that the responses of both regular and bursting neurons to parallel fiber stimulation are mediated by glutamate, acting mainly through non-NMDA receptors. Spontaneous activity of bursting, but not regular, neurons also requires non-NMDA glutamatergic transmission, suggesting that the spontaneous firing of bursting neurons, consisting largely of cartwheel cells, may depend upon granule cell activity.

2-Amino-5-phosphonovalerate↗
PubMed2002

Rapid deafferentation-induced upregulation of bcl-2 mRNA in the chick cochlear nucleus.

Neuronal survival in developing animals is often dependent on afferent activity. In the posthatch chick, approximately 30% of the neurons in the avian cochlear nucleus, nucleus magnocellularis (NM) die following elimination of VIIIth nerve activity. The factors that influence death or survival of an individual NM neuron are largely unknown. Previous studies indicate that both cell death and cell survival mechanisms compete to determine cell fate. One factor that has been shown to suppress cell death cascades in a variety of systems is bcl-2. If this gene product plays a role in regulating cell survival following deafferentation, then one might expect the expression of this gene to be influenced by removal of afferent input. In the present study, in situ hybridization revealed a rapid and transient increase in bcl-2 mRNA in NM neurons following deafferentation. Enhanced bcl-2 mRNA expression was observed at 6 and 12 h following deafferentation, but not at 3 or 24 h. Surprisingly, the upregulation of bcl-2 mRNA was limited to a subpopulation (20-30%) of deafferented neurons corresponding to the number of NM neurons that eventually die following cochlea removal. The robust and rapid upregulation of this gene suggests that cell death cascades regulated by bcl-2 may be initiated following deafferentation.

Animals↗
PubMed1997

Mitochondrial regulation of calcium in the avian cochlear nucleus.

The role of mitochondria and the endoplasmic reticulum in buffering [Ca2+]i in response to imposed calcium loads in neurons of the chick cochlear nucleus, nucleus magnocellularis (NM), was examined. Intracellular calcium concentrations were measured using fluorometric videomicroscopy. After depolarization with 125 mM KCl, NM neurons demonstrate an increase in [Ca2+]i that returns to near-basal levels within 6 min. Addition of the protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) dissipated the mitochondrial membrane potential, as evidenced by increased fluorescence when cells were loaded with rhodamine-123. Two micromolar CCCP had minimal effect on baseline [Ca2+]i. However, 2 or 10 microM CCCP interfered with the ability of NM cells to buffer [Ca2+]i in response to KCl depolarization without significantly affecting peak [Ca2+]i. Oligomycin also interfered with postdepolarization regulation of [Ca2+]i, but blocked late (7-8 min postdepolarization) increases in [Ca2+]i caused by CCCP. Thapsigargin had no effect on baseline, peak, or postdepolarization [Ca2+]i in NM cells. These results suggest that normal mitochondrial membrane potential and ATP synthesis play an important role in buffering [Ca2+]i in response to imposed calcium loads in NM neurons. Furthermore, the endoplasmic reticulum does not appear to play a significant role in either of these processes. Thus increases in mitochondrial number and function noted in NM cells after deafferentation may represent an adaptive response to an increased cytosolic calcium load.

Animals↗
PubMed2006

Temporal measures and neural strategies for detection of tones in noise based on responses in anteroventral cochlear nucleus.

To examine possible neural strategies for the detection of tones in broadband noise, single-neuron extracellular recordings were obtained from the anteroventral cochlear nucleus (AVCN) in anesthetized gerbils. Detection thresholds determined by average discharge rate and several temporal metrics were compared with previously reported psychophysical detection thresholds in cats (Costalupes 1985). Because of their limited dynamic range, the average discharge rates of single neurons failed to predict psychophysical detection thresholds for relatively high-level noise at all measured characteristic frequencies (CFs). However, temporal responses changed significantly when a tone was added to a noise, even for neurons with flat masked rate-level functions. Three specific temporal analyses were applied to neural responses to tones in noise. First, temporal reliability, a measure of discharge time consistency across stimulus repetitions, decreased with increasing tone level for most AVCN neurons at all measured CFs. Second, synchronization to the tone frequency, a measure of phase-locking to the tone, increased with tone level for low-CF neurons. Third, rapid fluctuations in the poststimulus time histograms (PSTHs) decreased with tone level for a number of neurons at all CFs. For each of the three temporal measures, some neurons had detection thresholds at or below psychophysical thresholds. A physiological model of a higher-stage auditory neuron that received simple excitatory and inhibitory inputs from AVCN neurons was able to extract the PSTH fluctuation information in a form of decreased rate with tone level.

Acoustic Stimulation↗
PubMed2003

The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons.

Using kinetic data from three different K+ currents in acutely isolated neurons, a single electrical compartment representing the soma of a ventral cochlear nucleus (VCN) neuron was created. The K+ currents include a fast transient current (IA), a slow-inactivating low-threshold current (ILT), and a noninactivating high-threshold current (IHT). The model also includes a fast-inactivating Na+ current, a hyperpolarization-activated cation current (Ih), and 1-50 auditory nerve synapses. With this model, the role IA, ILT, and IHT play in shaping the discharge patterns of VCN cells is explored. Simulation results indicate that IHT mainly functions to repolarize the membrane during an action potential, and IA functions to modulate the rate of repetitive firing. ILT is found to be responsible for the phasic discharge pattern observed in Type II cells (bushy cells). However, by adjusting the strength of ILT, both phasic and regular discharge patterns are observed, demonstrating that a critical level of ILT is necessary to produce the Type II response. Simulated Type II cells have a significantly faster membrane time constant in comparison to Type I cells (stellate cells) and are therefore better suited to preserve temporal information in their auditory nerve inputs by acting as precise coincidence detectors and having a short refractory period. Finally, we demonstrate that modulation of Ih, which changes the resting membrane potential, is a more effective means of modulating the activation level of ILT than simply modulating ILT itself. This result may explain why ILT and Ih are often coexpressed throughout the nervous system.

Action Potentials↗
PubMed1997

Rapid regulation of cytoskeletal proteins and their mRNAs following afferent deprivation in the avian cochlear nucleus.

During development, removal of neuronal input can lead to profound changes in postsynaptic cells, including atrophy and cell death. In the chicken brainstem cochlear nucleus, the nucleus magnocellularis (NM), deprivation of auditory input via unilateral cochlea removal or silencing the eighth nerve with tetrodotoxin leads to a loss of 25-30% of the neurons and the atrophy of surviving neurons. One intracellular component that may be involved in both cell atrophy and cell death is the cytoskeleton. The degradation of the cytoskeleton following deafferentation could potentially lead to either atrophy or death of NM neurons. However, little is known regarding the role of neuronal input on the cytoskeletal structure of NM neurons and whether changes in the cytoskeleton are responsible for cell death following deafferentation. The present study examined whether changes in the cytoskeleton of NM neurons occurred following cochlea removal. Several components of the cytoskeleton were analyzed following unilateral afferent deprivation. Levels of immunostaining for tubulin, actin, and microtubule-associated protein 2 (MAP-2), and levels of beta-tubulin and beta-actin mRNAs were assessed in NM neurons following cochlea removal. Our results revealed that afferent deprivation results in a rapid decrease in immunostaining for all three cytoskeletal proteins examined. These decreases were observed as early as 3 hours after cochlea removal and persisted for up to 4 days. In addition, these changes occurred in all deafferented NM neurons at the early time points, indicating that both dying and surviving NM neurons undergo a similar change in their cytoskeletons. In contrast to the decreases in immunostaining, levels of beta-tubulin and beta-actin mRNAs were not noticeably altered by deafferentation. Our findings indicate that the cytoskeleton is altered or degraded following deafferentation but that this process is not regulated at the transcriptional level.

Afferent Pathways↗
PubMed1988

Uptake and release of glycine in the guinea pig cochlear nucleus after axotomy of afferent or centrifugal fibers.

Glycine may be an inhibitory transmitter in the mammalian cochlear nucleus (CN). This study attempts to determine if cochlear and/or centrifugal projections to the CN use glycine as a transmitter. The high-affinity uptake and electrically evoked release of exogenous [14C]glycine were measured in vitro in the three major subdivisions of the guinea pig CN: the anteroventral, posteroventral, and dorsal cochlear nuclei (AVCN, PVCN, and DCN, respectively). [14C]Glycine (3.4 microM) was taken up by each subdivision, reaching tissue concentrations six to seven times that in the medium. Subsequent electrical stimulation evoked a Ca2+-dependent release of [14C]glycine from each subdivision. These activities were compared in subdivisions fr0m unlesioned animals, and from animals with lesions of centrifugal or cochlear projections to the CN. Two knife-cut lesions were made to interrupt centrifugal projections to the CN lying in the right acoustic striae and trapezoid body. In one group of animals, centrifugal fibers projecting mainly to the right AVCN and PVCN were severed, which reduced [14C]glycine uptake and release by 44-53% in these subdivisions, but not in the right DCN. In another group of animals, fibers projecting mainly to the right PVCN and DCN were severed, which reduced [14C]glycine uptake and release by 33-47% in these subdivisions, but not in the right AVCN. In CN subdivisions contralateral to either lesion there was no significant change in [14C]glycine uptake or release. Neither of these lesions altered the uptake or release of D-[3H]aspartate in the right or the left CN. Ablation of the left cochlea, which presumably destroyed cochlear nerve fibers unilaterally, had no effect on [14C]glycine uptake and release. These observations suggest that centrifugal projections contribute a proportion of the glycinergic synaptic endings in the CN. In addition, some glycinergic endings probably arise from neurons intrinsic to the CN. The cochlear nerve contains very few, if any, glycinergic fibers.

Afferent Pathways↗
PubMed1997

[Rapid functional plasticity of the neurons in the inferior colliculus and dorsal cochlear nucleus after brief exposure to intense pure tone].

The changes of response properties were observed from the single neuron in inferior colliculus (IC) and dorsal cochlear nucleus (DCN) located in the area bordering the lesion created by intense pure tone. The frequencies of traumatizing tone were chosen higher than the characteristic frequency (CF) of the neurons and beyond their excitatory response area so that the traumatizing tone would not influence the excitatory input to the neurons under study. Different types of disinhibition effects were found in more than half of the neurons after the traumatizing tone. The results indicated a subcortical origination of cortical functional reorganization and the involvement of lateral inhibition in the formation of inhibitory neural networks in both IC and DCN.

Acoustic Stimulation↗
PubMed2001

Survival and differentiation of neurons cultured from the mouse cochlear nucleus on extracellular matrix components.

This study was designed to determine the effects of several extracellular matrix (ECM) proteins on the survival and differentiation of cochlear nucleus (CN) neurons grown in primary cell culture. CN neurons were successfully grown on laminin, collagen and fibronectin, but neuronal survival was significantly decreased on all three substrates relative to poly-D-lysine controls. In addition, analysis of dendrite organization patterns indicated that CN neurons branched more extensively when grown on poly-D-lysine than on any of the ECM components tested. Although dendrite growth has been shown to depend strongly on the presence of ECM components in other neuronal systems, the data from these experiments do not support the hypothesis that laminin, collagen or fibronectin is necessary for the survival and differentiation of CN neurons.

Animals↗
PubMed2006

Contributions of Aage Møller in the study of the cochlear nucleus.

At a time when little was known about processing in the auditory system, Aage Møller undertook an extensive investigation of the response properties of cochlear nucleus (CN) neurons. With an excellent background in physiological acoustics and a command of computational techniques he systematically explored neural tuning, rate-level functions, and receptive fields of CN neurons using microelectrode recordings. He chose to employ more natural stimuli than just pure tones and employed a variety of stimuli consisting of tones, clicks, noise, amplitude- and frequency-modulated signals to document both intensity and temporal response characteristics. The response to noise stimuli was quantified using linear systems analysis which was very innovative at that time. By choosing to perform the studies in the white rat rather than cat, he provided important comparative data on this first center of the central auditory system. Over a span of ten years he provided a significant body of observations of CN units properties that has rarely been equaled.

Acoustic Stimulation↗
PubMedDate not supplied

The temporal window of two-tone facilitation in onset units of the ventral cochlear nucleus.

Effects of a tone, not at the best frequency (BF), on the responses of onset units to BF tones were recorded in the ventral cochlear nucleus of the guinea pig. The off-BF tone was at a fixed non-excitatory sound level. When the two tones were gated simultaneously, a marked threshold facilitation was observed; however, no facilitation was observed if the off-BF tone burst was delayed by 5-10 ms. Facilitation in some units declined and was either absent or only just detectable, when the start of the off-BF tone preceded that of the BF by more than 10 ms. However, the responses of the majority of onset units were facilitated when the off-BF tone preceded the BF tone by as much as 20 ms. Similar results were obtained when the roles of the BF and off-BF tones were reversed. These data suggest that depolarization due to BF inputs is of shorter duration than that due to off-BF inputs.

Animals↗