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PubMed1997

Changes in the tonotopic map of the dorsal cochlear nucleus in hamsters with hair cell loss and radial nerve bundle degeneration.

Hamsters were exposed to an intense tone (10 kHz) at levels and durations sufficient to cause hair cell loss and radial nerve bundle degeneration. A previous study reported changes in the tonotopic map of the dorsal cochlear nucleus (DCN) in hamsters with tone-induced stereocilia loss. Such changes appear similar to those observed by others in the auditory nerve following acoustic trauma, and suggest that the map alterations have a peripheral origin. However, the potential for tonotopic map reorganization after more severe lesions involving cellular degeneration in the cochlea has not yet been determined. The purpose of the present study was to determine how the tonotopic map of the DCN appears in animals with severe cochlear injury involving hair cell loss and radial nerve bundle degeneration. Neural population thresholds and tonotopic organization were mapped over the surface of the DCN in normal unexposed animals and those showing tone-induced lesions. The results indicate that cochlear lesions characterized mainly by radial bundle degeneration in a restricted portion of the organ of Corti cause changes in a corresponding region of the tonotopic map which reflect primarily changes in the shape and thresholds of neural tuning curves. In many cases the center of the lesion was represented in the DCN as a distinct characteristic frequency (CF) gap in the tonotopic map in which responses were either extremely weak or absent. In almost all cases the map area representing the center of the lesion was bordered by an expanded region of near-constant CF, a feature superficially suggestive of map reorganization (i.e., plasticity). However, these expanded map areas had abnormal tip thresholds and showed other features suggesting that their CFs had been shifted downward by distortion and deterioration of their original tips. Such changes in neural tuning following tone-induced loss of anatomical input to the central auditory pathway are similar to those observed in our previous study and by others in the auditory nerve following less severe acoustic trauma, and thus would seem to have a peripheral origin. Thus, changes in the DCN tonotopic map can be explained by peripheral modifications and do not seem to involve plastic changes (i.e., reorganization).

Acoustic Stimulation↗
PubMed2005

Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus.

Tinnitus displays many features suggestive of plastic changes in the nervous system. These can be categorized based on the types of manipulations that induce them. We have categorized the various forms of plasticity that characterize tinnitus and searched for their neural underpinnings in the dorsal cochlear nucleus (DCN). This structure has been implicated as a possible site for the generation of tinnitus-producing signals owing to its tendency to become hyperactive following exposure to tinnitus inducing agents such as intense sound and cisplatin. In this paper, we review the many forms of plasticity that have been uncovered in anatomical, physiological and neurochemical studies of the DCN. Some of these plastic changes have been observed as consequences of peripheral injury or as fluctuations in the behavior and chemical activities of DCN neurons, while others can be induced by stimulation of auditory or even non-auditory structures. We show that many parallels can be drawn between the various forms of plasticity displayed by tinnitus and the various forms of neural plasticity which have been defined in the DCN. These parallels lend further support to the hypothesis that the DCN is an important site for the generation and modulation of tinnitus-producing signals.

Cochlear Nerve↗
PubMed1991

Synaptic organization of globular bushy cells in the ventral cochlear nucleus of the cat: a quantitative study.

The synaptic organization of globular bushy cells of the anteroventral cochlear nucleus was quantitatively analyzed in order to understand better their functional attributes. A method was devised to estimate the concentrations and relative proportions of synapses on the entire postsynaptic surface of Golgi-impregnated neurons, by sampling with limited series of sections for electron microscopy. This provided a characteristic synaptic profile which was homogeneous for the population measured. The total concentration of synaptic endings decreases with distance from the soma. The cochlear, presumably glutamatergic and excitatory, endings with large spherical vesicles (LS) account for most of this decrease. Of the noncochlear inputs, the putative glycinergic endings with flattened vesicles (FL) decrease slightly, and the presumed GABAergic terminals with pleomorphic vesicles (PL) maintain a relatively constant concentration, while endings with small spherical vesicles (SS) increase on the distal dendrites. LS endings have the largest proportion of synapses near the soma, while FL synapses maintain a constant proportion in all cell regions, and PL and SS proportions increase on higher-order dendrites. Excitatory and inhibitory synapses have significant inputs to the axon hillock and initial segment, as well as to the distal dendrites, where dual synapses may provide a way to sample the activity of surrounding neurons. These features must be considered in explanations of physiological properties, such as the synaptic security, level of spontaneous activity, and well-timed, rapid onset responses, as well as their potential for normalizing and synchronizing an important inhibitory pathway involved in binaural signal processing. Synaptic profile analysis should be useful for experimental studies and for developing realistic computational models.

Afferent Pathways↗
PubMed1980

Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons.

The effects of conditioning stimulation of the locus coeruleus (LC) on the neuron activity of dorsal cochlear nucleus (DCN), which is rich in noradrenergic nerve terminals, were compared with those on the lateral vestibular nucleus (LVN), devoid of such terminals, to determine whether or not noradrenaline is responsible for the LC-induced inhibition. The conditioning stimuli applied to the LC had no effect on either the field potential or the spike generation of mono- and polysynaptic neurons in the LVN elicited by VIIIth cranial nerve stimulation. In contrast, the spike firing of the DCN neurons with VIIIth cranial nerve stimulation was significantly inhibited by LC conditioning stimulation. The inhibition of spike generation was mainly observed in the DCN neurons which fired spikes with a longer latency. The inhibition of DCN neurons by LC conditioning stimulation did not occur in the cats pretreated with reserpine; however, a rapid recovery of the inhibition was produced by intraventricular application of noradrenaline. These results are in good agreement with the histochemical findings and support our previous conclusion that noradrenaline acts as an inhibitory transmitter or modulator on the nuclei where noradrenergic nerve terminals derived from the LC are located. In addition, the vestibular input in the primary relay nucleus is apparently not regulated by noradrenaline originating in the LC.

Animals↗
PubMed1989

Rapid changes in cochlear nucleus cell size following blockade of auditory nerve electrical activity in gerbils.

Large spherical cells of the mammalian anteroventral cochlear nucleus (AVCN) receive direct excitatory input from auditory nerve axons. Trans-synaptic regulation of neuronal cell size and cell number after cochlear ablation has been previously demonstrated in neonates of several vertebrate species, including the gerbil. Such changes may be related to loss of spontaneous or evoked auditory nerve electrical activity or to loss of activity-independent factors. We have developed a method to chronically, yet reversibly, block auditory nerve electrical activity without violating the integrity of the inner ear. Tetrodotoxin (TTX) was embedded in an ethylene-vinyl acetate copolymer resin (Elvax). A small piece of Elvax containing TTX was placed next to the round window membrane, which allowed TTX to diffuse into the inner ear. As a measure of the effectiveness of manipulation, the onset, duration, and magnitude of the auditory threshold shift were measured by the auditory brainstem response. The sound-evoked response was abolished within 10 minutes of placement of TTX on the round window membrane. The duration of threshold shift was dose-dependent and lasted 24-46 hours. Implants of Elvax without TTX did not produce a significant threshold shift. TTX, which blocks voltage-gated sodium channels, did not abolish the potassium-based cochlear microphonic response. The consequence of blocking afferent electrical activity on gerbil AVCN large spherical cells was examined by measuring their cross-sectional area after each of four manipulations: unilateral auditory nerve action potential blockade with TTX; unilateral surgical cochlear ablation; ipsilateral TTX exposure/contralateral cochlear ablation; and unilateral sham operation (Elvax without TTX).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

The dorsal cochlear nucleus of the adult lurcher mouse is specifically invaded by embryonic grafted Purkinje cells.

The fate of embryonic Purkinje cells grafted over the brainstem surface of the adult Lurcher mouse was analyzed using anti-calbindin (CaBP) immunocytochemistry. Purkinje cells are able to migrate specifically into the molecular layer of the host dorsal cochlear nucleus (DCoN) and develop dendritic trees that are practically isoplanar, suggesting synaptic interactions with the parallel fibres of the DCoN. These results provide a new argument in favour of the homology between the cerebellum and the DCoN.

Animals↗
PubMed1997

Differences between guinea pig and rat in the dorsal cochlear nucleus: expression of calcium-binding proteins by cartwheel and Purkinje-like cells.

This study describes differences between guinea pig and rat in the immunoreactivities for calbindin (CB-IR) and parvalbumin (PV-IR) in cartwheel (CWC) and Purkinje-like (PLC) cells of the dorsal cochlear nucleus (DCN). CWCs are the most important inhibitory interneurons of the DCN. Their soma and dendrites stain intensely for CB-IR in guinea pigs but only weakly and incompletely in rats. In both species, the CWCs do not show PV-IR. PLCs, a rare type of DCN cells often interpreted as displaced cerebellar Purkinje cells misrouted during migration, are known from rat and mouse and are here described for guinea pig DCN. PLCs are intensely and completely stained for CB-IR and PV-IR in guinea pigs. In rats, they stain with similar completeness only for CB-IR, PV-IR being weak and restricted to the cell's soma. Similar staining differences between the two species are seen with the cerebellar Purkinje cells, i.e., PLCs resemble the cerebellar Purkinje cells more than do the CWCs. Based on the present material (and preliminary findings in a primate (marmoset), we speculate that the PLCs have their place in the circuitry of the DCN receiving input via parallel fibers, like the CWCs, and possibly projecting their axon onto the cerebellum.

Animals↗
PubMed2001

Far-field responses to stimulation of the cochlear nucleus by microsurgically placed penetrating and surface electrodes in the cat.

OBJECT: A new generation of penetrating electrodes for auditory brainstem implants is on the verge of being introduced into clinical practice. This study was designed to compare electrically evoked auditory brainstem responses (EABRs) to stimulation of the cochlear nucleus (CN) by microsurgically implanted surface electrodes and insertion electrodes (INSELs) with stimulation areas of identical size. METHODS: Via a lateral suboccipital approach, arrays of surface and penetrating microelectrodes with geometric stimulation areas measuring 4,417 microm2 (diameter 75 microm) were placed over and inserted into the CN in 10 adult cats. After recording the auditory brainstem response (ABR) at the mastoid process, the CN, and the level of the inferior colliculus, EABRs to stimulation of the CN were recorded using biphasic, charge-balanced stimuli with phase durations of 80 microsec, 160 microsec, and 240 microsec at a repetition rate of 22.3 Hz. Waveform, threshold, maximum amplitude, and the dynamic range of the responses were compared for surface and penetrating electrodes. The EABR waveforms that appeared for both types of stimulation resembled each other closely. The mean impedance was slightly lower (30 +/- 3.4 kohm compared with 31.7 +/- 4.5 kohm, at 10 kHz), but the mean EABR threshold was significantly higher (51.8 microA compared with 40.5 microA, t = 3.5, p = 0.002) for surface electrode arrays as opposed to penetrating electrode arrays. Due to lower saturation levels of the INSEL array, dynamic ranges were almost identical between the two types of stimulation. Sectioning of the eighth cranial nerve did not abolish EABRs. CONCLUSIONS: Microsurgical insertion of electrodes into the CN complex may be guided and monitored using techniques similar to those applied for implantation of surface electrodes. Lower thresholds and almost equivalent dynamic ranges indicate that a more direct access to secondary auditory neurons is achieved using penetrating electrodes.

Animals↗
PubMed2005

Hazard functions and expected spike density functions for neuron spike activity in the cochlear nucleus of the cat.

The goal of these experiments was to evaluate the effect of stimulus evoked input and post spike refractoriness on the shapes of post stimulus time histograms (PSTHs). The time courses of spontaneous and/or evoked activity were studied in 153 neurons located predominantly in the dorsal cochlear nucleus in cats anesthetized with Nembutal. Tone bursts were presented to the ipsilateral ear in a free sound field. About half the cells were characterized by the pauser/build-up type of PSTH. Marked refractoriness was evidenced by relatively long recovery times of the hazard functions of spontaneous and tone-evoked spike activity. On presentation of tonal bursts, the time dependence of the probability of the first spike in the absence of a preceding spike (expected spike density function) was greater than the PSTH (actual spike density function). The initial PSTH peak with pause was shaped primarily by stimulus evoked input, whereas refractoriness tended to diminish the build-up portion of the PSTH. In chopper cells, PSTH peaks were usually not reflected in expected spike density functions showing that post spike refractoriness plays a major role in shaping the PSTH. In primary-like cells, refractoriness was small and had little effect on the shape of the PSTH. Some presumptively inhibitory cells showed a tendency to burst discharges with non-monotonic hazard functions. A very small number of cells showed a tendency to internal tuning to a defined signal periodicity.

Acoustic Stimulation↗
PubMed1990

Neural coding in the chick cochlear nucleus.

Physiological recordings were made from single units in the two divisions of the chick cochlear nucleus-nucleus angularis (NA) and nucleus magnocellularis (NM). Sound evoked responses were obtained in an effort to quantify functional differences between the two nuclei. In particular, it was of interest to determine if nucleus angularis and magnocellularis code for separate features of sound stimuli, such as temporal and intensity information. The principal findings are: 1. Spontaneous activity patterns in the two nuclei are very different. Neurons in nucleus angularis tend to have low spontaneous discharge rates while magnocellular units have high levels of spontaneous firing. 2. Frequency tuning curves recorded in both nuclei are similar in form, although the best thresholds of NA units are about 10 dB more sensitive than their NM counterparts across the entire frequency range. A wide spread of neural thresholds is evident in both NA and NM. 3. Large driven increases in discharge rate are seen in both NA and NM. Rate intensity functions from NM units are all monotonic, while a substantial percentage (22%) of NA units respond to increased sound level in a nonmonotonic fashion. 4. Most NA units with characteristic frequencies (CF) above 1000 Hz respond to sound stimuli at CF as 'choppers', while units with CF's below 1000 Hz are 'primary-like'. Several 'onset' units are also seen in NA. In contrast, all NM units show 'primary-like' response. 5. Units in both nuclei with CF's below 1000 Hz show strong neural phase-locking to stimuli at their CF. Above 1000 Hz, few NA units are phase-locked, while phase-locking in NM extends to 2000 Hz. 6. These results are discussed with reference to the hypothesis that NM initiates a neural pathway which codes temporal information while NA is involved primarily with intensity coding, similar in principle to the segregation of function seen in the cochlear nucleus of the barn owl (Sullivan and Konishi 1984).

Acoustic Stimulation↗
PubMed1994

Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency.

1. Encoding temporal features of the acoustic waveform is an important attribute of the auditory system. Auditory nerve (AN) fibers synchronize or phase-lock to low-frequency tones and transmit this temporal information to cells in the anteroventral cochlear nucleus (AVCN). Phase-locking in the AVCN is usually reported to be similar to or weaker than in the AN. We studied phase-locking in axons of the trapezoid body (TB), which is the output tract of the AVCN, and found, to our surprise, that most TB axons exhibited enhanced synchronization compared with AN fibers. 2. Responses from axons in the TB of the cat were obtained with horseradish peroxidase (HRP)- or Neurobiotin-filled micropipettes or metal microelectrodes. A series of short tone bursts at increasing sound pressure level (SPL) was presented at the characteristic frequency (CF) of the fiber and phase-locking was quantified with the vector strength R at each SPL. For each fiber the maximum R value (Rmax) was then determined. 3. Low-frequency fibers in the TB showed very precise phase-locking: Rmax values could approach 0.99. For the majority of fibers (33/44, 75%) with CF < 700 Hz, Rmax was > or = 0.9 and therefore higher than is ever observed in the AN. We define such fibers as "high-sync." Most of these fibers also entrained to the stimulus, i.e., they fired a precisely timed action potential to almost every stimulus cycle. Some fibers showed perfect entrainment, with maximum discharge rates equaling the stimulus frequency. 4. To exclude the possibility that stimulus paradigms or acoustic and recording equipment were the source of this enhancement, we obtained additional data on low-frequency AN fibers using the same experimental protocol as in our TB experiments. These AN data agree well with published reports. 5. The morphological class of some of the cells studied was identified on the basis of anatomic features revealed by intra-axonal injection of HRP or Neurobiotin. Labeled low-CF axons (N = 7), which were all high-sync, originated from AVCN bushy cells: five were globular and two were spherical bushy cell axons. 6. Spontaneous rate of high-sync fibers covered a range from 0 to 176 spikes/s but were biased toward low values (mean 16 spikes/s). Responses to broadband clicks and sinusoidally amplitude-modulated signals provided additional evidence of improved timing properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Metabotropic glutamate receptor activation modulates sound level processing in the cochlear nucleus.

The principal role of ionotropic glutamate receptors in the transmission and processing of information in the auditory pathway has been investigated extensively. In contrast, little is known about the functional contribution of the G-protein-coupled metabotropic glutamate receptors (mGluRs), although their anatomic location suggests that they exercise a significant influence on auditory processing. To investigate this issue, sound-evoked responses were obtained from single auditory neurons in the cochlear nuclear complex of anesthetized cats and gerbils, and metabotropic ligands were administered locally through microionophoretic pipettes. In general, microionophoresis of the mGluR agonists, (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid or (2S,1'S, 2'S)-2-(carboxycyclopropyl)glycine, initially produced a gradual increase in spontaneous and sound-evoked discharge rates. However, activation and recovery times were significantly longer than those observed for ionotropic agonists, such as N-methyl--aspartate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, consistent with the recruitment of a second-messenger system. The efficacy of mGluR agonists was diminished after administration of the mGluR antagonist, (+)-alpha-methyl-4-carboxyphenylglycine, consistent with a selective action at metabotropic recognition sites. In contrast, two distinct changes were observed after the mGluR agonist had been discontinued for several minutes. Approximately 50% of neurons exhibited a chronic depression of sound-evoked discharge rate reminiscent of long-term depression, a cellular property observed in other systems. Approximately 30% of neurons exhibited a long-lasting enhancement of the sound-evoked response similar to the cellular phenomenon of long-term potentiation. These findings suggest that mGluR activation has a profound influence on the gain of primary afferent driven activity in the caudal cochlear nucleus.

Acoustic Stimulation↗
PubMed2006

Convergence of spinal trigeminal and cochlear nucleus projections in the inferior colliculus of the guinea pig.

In addition to ascending auditory inputs, the external cortex of the inferior colliculus (ICX) receives prominent somatosensory inputs. To elucidate the extent of interaction between auditory and somatosensory representations at the level of IC, we explored the dual projections from the cochlear nucleus (CN) and the spinal trigeminal nucleus (Sp5) to the inferior colliculus (IC) in the guinea pig, using both retrograde and anterograde tracing techniques. Injections of retrograde tracers into ICX resulted in cell-labeling primarily in the contralateral DCN and pars interpolaris and caudalis of Sp5. Labeled cells in DCN were either fusiform or multipolar cells, whereas those in Sp5 varied in size and shape. Injections of anterograde tracers into either CN or Sp5 resulted in terminal labeling in ICX primarily on the contralateral side. Most projection fibers from Sp5 terminated in a laminar pattern from ventromedial to dorsolateral within the ventrolateral ICX, the ventral border of IC, and the ventromedial edge of IC (collectively termed "the ventrolateral border region of IC," ICXV). Less dense anterograde labeling was observed in lateral and rostral ICX. Injecting different tracers into both Sp5 and CN confirmed the overlapping areas of convergent projections from Sp5 and CN in IC: The most intense dual labeling was seen in the ICXV, and less intense dual labeling was also observed in the rostral part of ICX. This convergence of projection fibers from CN and Sp5 provides an anatomical substrate for multimodal integration in the IC.

Afferent Pathways↗
PubMed1989

Open-set minimum auditory capability scores for House and Nucleus cochlear prostheses.

This study addresses the following questions: Is there a difference in open-set recognition among patients using House and Nucleus devices? How many subjects are needed to determine statistically significant differences between devices? The subjects were 12 patients, six with House and six with Nucleus cochlear prostheses. Using open-set tests from the Minimum Auditory Capabilities Battery, the Nucleus group had significantly better scores than the House device group. Our sample size was adequate in part because the House device group scored near zero. To determine moderate differences between groups with scores of 10% or better, approximately 20 paired or 60 unpaired subjects would be needed in each group.

Adult↗
PubMed1996

Processing of modulation frequency in the dorsal cochlear nucleus of the guinea pig: sinusoidal frequency-modulated tones.

Frequency- and amplitude-modulated (FM and AM, respectively) tones are important information-bearing elements in voice sounds and can also be produced by the spatial movement of sound sources. Zhao and Liang (1995) recently reported the response features of dorsal cochlear nucleus (DCN) neurons to AM tones. In the present study, the responses of the guinea pig DCN neurons to sinusoidal FM (SFM) tones were examined. Discharges of the DCN units to the SFM tones phase-locked to the stimulus modulation frequencies (fm). The phase-locked discharge patterns existed over broad ranges of modulation parameters and at stimulus levels as high as 95 dB SPL or modulation depths (dm) as low as 2%. Robust phase-locking to the fm was observed in samples of all DCN unit types studied. The means of best fm (Bfm) and upper limit fm (ULfm) of all recorded units were 510 Hz and 940 Hz, respectively. Pauser/Buildup (P/B) units had mean maximum synchronization index (SImax) of 0.57. ON units had the highest Bfm with the mean of 646 Hz and subtype ON-S showed the highest mean of SImax at 0.63. Phase-locking to the fm was independent of discharge rates and existed even when the discharge rates were reduced to the background spontaneous rate (SR). A few units showed stronger synchronous responses to the square and triangular FM stimuli instead of the SFM tones. The relationship between the modulated responses and the unit's response area were further examined. The fm phase-locking occurred to modulation bands (or frequency ranges) within the response area, with the modulation bands as narrow as +/- 160 Hz in the central inhibitory areas of the type IV units. As the width of the modulation band changed within a unit's response area, the phases of the fm phase-locked responses of P/B units linearly changed while for Onset units, the change was lesser. The P/B and Onset units had a pi phase shift and a pi/2 phase change, respectively, as carrier frequencies (fc5) passed through characteristic frequencies (CF) and the excitatory/inhibitory response boundaries. The phase-locked responses to the fms were dependent on the SR but were independent of the CF. Low-SR (< or = 2 spikes/s) units had higher synchronization of responses to the fm than the high-SR (> 2 spikes/s) units (SImax = 0.64 and 0.42 respectively). These results suggest that the temporal characteristics of the fm is effectively represented in the responses of DCN units to the SFM tones. Such temporal encoding behavior can play an important role in the processing of the complex sounds in the auditory system. These results also have implications for a possible role for the DCN is in identifying the spatial movement of a sound source.

Acoustic Stimulation↗
PubMed1995

Patterns of GFAP-immunoreactivity parallel the tonotopic axis in the developing dorsal cochlear nucleus.

The role of glia in the development of tonotopic and laminar organization in the auditory central nervous system has not been well characterized. In other systems, glia immunoreactive for glial fibrillary acidic protein (GFAP) appear to function in development of radial, laminar and topographic organization. Using a polyclonal antibody to GFAP, we have characterized the development of GFAP-immunoreactivity in the dorsal cochlear nucleus (DCN), a laminated and tonotopically organized central auditory system structure. Results suggest that in this nucleus, the GFAP-immunoreactive processes are not found within or between developing laminae, rather glial processes are observed parallel to presumptive isofrequency sheets before primary afferents have invaded the nucleus. Thus, GFAP-immunoreactive processes are positioned to play an early role in establishing the tonotopic axis of the DCN.

Animals↗