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Influence of centrifugal pathways on forward masking of ventral cochlear nucleus neurons.

When responses to one part of a sequence of auditory signals reduce the responses to a subsequent portion of the signal, "forward masking" results. Although forward masking occurs in the auditory nerve, that observed in the ventral cochlear nucleus (VCN) more closely resembles psychophysical forward masking. In contrast to the auditory nerve in which the amount of forward masking is proportional to the amount of excitation produced by the masker, most VCN neurons show a poor correlation between forward masking and excitation produced by the masker, indicating a more complex interaction between responses to adjacent signals. This study tested the hypothesis that one component of forward masking is produced by inputs from centrifugal neural connections to the VCN. The centrifugal pathways were interrupted with knife-cut lesions medial to the CN. Responses of single units obtained 60 minutes after the lesions were compared to those obtained before the lesions. In primarylike, sustained chopper and on units the lesions resulted in a reduction in forward masking and enhanced recovery. In contrast, lesions resulted in increased masking in primarylike-notch and low-intensity chopper units. The relationship between masker-elicited excitation and forward masking became more monotonic for transient choppers and on units, approaching that observed for auditory nerve fibers. These effects are probably the result of removal of both inhibitory and excitatory inputs, ultimately reflecting a balance of excitation and inhibition to each neural population in the VCN.

Animals↗

Signs of functional maturation of peripheral auditory system in discharge patterns of neurons in anteroventral cochlear nucleus of kitten.

1. Responses to pure tones were recorded from single neurons in the anteroventral cochlear nucleus (AVCN) in kittens ranging in age from 4 to 45 days. Different response properties mature at different times after birth. 2. The shapes of response areas of AVCN neurons after the 1st postnatal week resemble those recorded in the AVCN and auditory nerve of the adult. During the 1st wk after birth the high-frequency portion of the response area is extended. Phase-locked responses to stimulus frequencies below about 600 Hz occur at this time. Phase vs. frequency measurements and shapes of response areas indicate that by the end of the 1st postnatal week the cochlear partition may be capable of supporting a traveling wave along most of its length. 3. Functional development proceeds through a second phase which lasts until the end of the 2nd or the beginning of the 3rd wk of life. During that time threshold, maximal discharge rate, and average first-spike latency achieve adult values. 4. Phase-locking to low-frequency tones, to the extent displayed by phase-sensitive neurons in the adult AVCN or auditory nerve, is achieved last, after the 3rd or 4th wk postpartum.

Age Factors↗

Morphology of the octopus cell area of the cochlear nucleus in young and aging C57BL/6J and CBA/J mice.

The influence of aging and age-related cochlear impairment on the ventral cochlear nucleus was evaluated by measuring morphological properties of the octopus cell area (OCA) in five age groups of inbred C57BL/6J and CBA/J mice (young adult to very old). The former strain demonstrates progressive cochlear sensorineural pathology and hearing loss during middle age; the latter has only modest sensorineural pathology late in life. Histological sections of the OCA were evaluated with serial sections and several strains for neurons, glia, and fibers, and Golgi impregnations were also used. Aging was associated with a decrease in volume of the OCA, a loss of neurons, slight decrease in neuron size, increased packing density of glial cells, and changes in dendrites ranging from minor to total loss of primary branches. The greatest changes occurred in extreme old age, beyond the median lifespan. Age-related changes were not exacerbated by sensorineural pathology in aging C57BL/6J mice. Individual octopus cells varied greatly in the extent of age-related abnormality.

Aging↗

Projections from the anterior ventral cochlear nucleus to the central nucleus of the inferior colliculus in young and aging C57BL/6 mice.

Projections from the anterior ventral cochlear nucleus (AVCN) to the central nucleus of the inferior colliculus (ICC) were studied in young and aging C57BL/6 mice. The latter animals demonstrate progressive loss of hearing. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the inferior colliculus and retrograde transport to the AVCN sections, quality of labelling, number of labelled neurons adjusted for injection size, or topographic organization of projections. Thus, despite progressing loss of auditory sensitivity, chronic profound hearing loss (oldest animals), and aging, projections from AVCN to ICC remain stable.

Aging↗

Single-unit recording in the ventral cochlear nucleus of behaving cats.

A method is described for single-unit recording in the ventral cochlear nucleus (VCN) of behaving cats. Five cats were implanted with titanium head-restraint devices and acetal plastic recording chambers. The recording chamber directed microelectrodes through the cerebellum and into the VCN. Electrophysiological recordings were obtained from isolated VCN units while the cats engaged in an auditory discrimination task. The task required the cats to discriminate changes in the temporal pattern of a series of tone or noise bursts. Cats initiated the testing sequence by depressing a lever, and obtained food by releasing the lever when the pattern of stimuli changed from one 200-ms burst/s to four 50-ms bursts/s. Stimulus features (i.e., frequency, level, duration) were manipulated to characterize the physiological responses of VCN units. Preliminary data suggest that peri-stimulus time histograms (PSTHs) and rate-level functions (RALVs) obtained from behaving cats are similar to those previously described in anesthetized and decerebrate cats when units are tested with tones in quiet backgrounds. However, in comparison to anesthetized and decerebrate cats, units obtained in behaving cats demonstrate a more sensitive rate representation of stimulus level when tested in continuous background noise.

Acoustic Stimulation↗

Physiological studies on neurons in the dorsal cochlear nucleus of cat.

Results reported here support the conclusion that an individual neuron in the dorsal cochlear nucleus (DCN) can exhibit pauser, buildup, and chopper patterns in response to tone pips. Fusiform cells have been previously identified as the principal cell exhibiting these patterns. Fusiform cells can also exhibit an onset response followed by suppression of spontaneous activity at their characteristic frequency (CF). Off CF only suppression is seen. These neurons are characterized by a restricted excitatory region near threshold. All these cells can exhibit nonmonotonic rate curves, narrow excitatory regions, and inhibitory sidebands. Nonmonotonicity occurred in 34% of pausers, 52% of buildup, 89% of onsets with a graded response, and 50% overall in the DCN cells. Chopper units occur as often as the other types combined in the DCN. Only 14% show nonmonotonic rate curves. Those with high-spontaneous activity also show inhibitory sidebands. Cells with a predominant buildup pattern occur most frequently in the fusiform cell layer, whereas pausers occur throughout the DCN below the molecular layer. Intracellular potentials often reflect the average response pattern. Sharply delimited response areas indicate that these cells may be useful for performing a spectral analysis. These cells show almost no phase locking suggesting that temporal encoding is an unlikely function. It is suggested that the effects of anesthetic on the function of the DCN is not as marked as previously indicated.

Acoustic Stimulation↗

Rhythmic discharge properties of caudal cochlear nucleus neurons during postnatal development in cats.

Action potentials recorded extracellularly from neurons within the caudal cochlear nuclei of developing cats exhibited distinctive temporal characteristics (i.e., rhythmic responses) in response to long-duration acoustic stimuli including both tone and noise bursts. Unlike the homogeneous response characteristics of auditory nerve fibers, cochlear nucleus neurons exhibited many variations in rhythmic discharge patterns. The majority of neurons within the caudal CN of kittens younger than 10 days of age responded rhythmically to long-duration acoustic stimuli, however, the percentage of neurons responding rhythmically steadily decreased thereafter, and by the end of the second postnatal week most tonically-responding neurons maintained sustained steady-state discharge rates throughout stimulation. Discharges of neurons recorded during the transitional ages (around 13 days) were rhythmic at low sensation levels and exhibited adultlike sustained patterns at higher levels. Using constant sensation level stimuli (re individual neuron thresholds), burst frequencies remained essentially constant during the period of development in which rhythmic responses were observed. Intervals separating discharge bursts decreased as stimulus intensities increased for all neurons studied during the relevant period, but were not related in an orderly way to stimulus frequency. The effects of intensity on response periodicity were not mimicked by altering the amount of neurotransmitter present at the postsynaptic cell through microiontophoresis of excitatory amino acids and their antagonists onto the surface of neurons within the caudal CN. In addition, some immature neurons which responded phasically to acoustic stimuli responded rhythmically during the simultaneous presentation of acoustic stimuli and neuroexcitatory agents (i.e., glutamate). These results suggest that the source of the rhythmicity is not intrinsic to neurons in the caudal CN. Based on these and other observations we conclude that the most probable source of response periodicity observed early in development is the domination of inner hair cell output by efferent projections of the olivocochlear bundle, the temporal discharge patterns of which are also periodic.

Age Factors↗

Evidence of a functionally segregated pathway from dorsal cochlear nucleus to inferior colliculus.

Type O units in the central nucleus of the inferior colliculus (ICC) of decerebrate cats are excited by best frequency (BF) tones near threshold, but are inhibited by high-level tones at all frequencies. Dorsal cochlear nucleus (DCN) principal cells display similar response map features and project directly to the ICC, and are thus supposed to be the dominant source of excitatory input for type O units. To test this hypothesis, the responses of type O units were compared before and after two pharmacological manipulations. When DCN to ICC axons were blocked by pressure injections of lidocaine, most type O units (approximately 80%) were silenced or showed substantially reduced activity, but some units showed increased activity. All of the former units had low maximal rates to BF tones, whereas the latter units had high rates. When local circuit inhibitory mechanisms in the ICC were blocked by iontophoretic application of bicuculline or strychnine, type O unit responses also fell into two classes: low-rate units that showed increased spontaneous and driven activities and high-rate units that showed, in addition, altered response map features. Taken together, these results demonstrate that low-rate type O units are part of a functionally segregated pathway initiated by the DCN, whereas high-rate type O units are created at the level of the ICC.

Acoustic Stimulation↗

Effect of cochlear integrity on cochlear nucleus neuron glucose metabolism in aged adult broiler chickens.

Abrupt removal of excitatory input is devastating to post-synaptic neurons in normally functioning sensory systems. In both mammalian and avian auditory systems, abrupt temporary or permanent experimental deafferentation stimulates a cascade of changes in central auditory structures that can result in neuron death. Effects of naturally occurring progressive deafferentation on central auditory structure and function have not been fully described. Extensive naturally occurring cochlear damage is found in some aged chickens, despite their regenerative capacity, providing the opportunity to examine the effects of this type of deafferentation on the avian cochlear nucleus (nucleus magnocellularis, NM). Previous evaluation of NM oxidative metabolism using cytochrome oxidase histochemistry revealed that naturally occurring cochlear damage results in down-regulated metabolism in corresponding regions of NM. It is unknown how progressive hair cell damage and loss affects NM glucose uptake. Here, NM glucose metabolism is assessed using 2-deoxyglucose uptake as a marker for metabolic activity in the presence of normal, mildly damaged, severely damaged, and totally damaged cochlear hair cells. Results indicate that while severe and total cochlear damage significantly decrease NM oxidative metabolism, only total damage results in significantly decreased NM glucose metabolism. Results are discussed in the context of functional reorganization and trophic support.

Aging↗

Multimodal inputs to the granule cell domain of the cochlear nucleus.

There is growing evidence that hearing involves the integration of many brain functions, including vision, balance, somatic sensation, learning and memory, and emotional state. Some of these integrative processes begin at the earliest stages of the central auditory system. In this review, we will discuss evidence that reveals multimodal projections into the granule cell domain of the cochlear nucleus.

Animals↗

The total number of neurons and calcium binding protein positive neurons during aging in the cochlear nucleus of CBA/CaJ mice: a quantitative study.

The quantitative stereological method, the optical fractionator, was used for determining the total number of neurons and the total number of neurons immunostained with parvalbumin, calbindin-D28k (calbindin), and calretinin in the dorsal and posteroventral cochlear nucleus (DCN and PVCN) in CBA/CaJ (CBA) mice during aging (1-39 months old). CBA mice have only a modest sensorineural pathology late in life. An age-related decrease of the total number of neurons was demonstrated in the DCN (r=-0.54, P<0.03), while the total number of neurons in the PVCN did not show any significant age-related differences (r=0.16, P=0.57). In the DCN 5.5% of neurons were parvalbumin positive in the very old (30-39 months) mice, vs. 2.2% in the 1 month old mice. In the DCN 3% of the neurons were calbindin immunopositive in the 30-39 months mice compared to 1.9% in the 1 month old group. In the PVCN, 20% of the neurons in the very old mice were parvalbumin immunopositive, compared to 12% in the young mice. Calbindin did not show any significant age-related differences in the PVCN. The total number of calretinin immunopositive neurons both in the DCN and PVCN did not show any significant change with increasing age. In conclusion, the total neuronal number in the DCN and PVCN was age-related and region-specific. While the neuronal number in the DCN and PVCN was decreased or unchanged, respectively, the calcium binding protein positive neuronal number showed a graded increase during aging in a region-specific and protein-specific manner.

Aging↗

Strychnine alters the fusiform cell output from the dorsal cochlear nucleus.

Anatomical and physiological evidence suggests that fusiform cells, the major output neurons of the dorsal cochlear nucleus (DCN), receive significant inhibitory input. Fusiform cells often display strongly non-monotonic rate-intensity functions and pauser-buildup or buildup tone-evoked temporal responses, patterns which may be mediated by inhibitory neurotransmitters. Other neurons located within the fusiform cell layer or in the more superficial molecular layer display varied rate-intensity functions and temporal responses. Neurons displaying response properties characteristic of fusiform cells are sensitive to iontophoretic application of the inhibitory amino acid neurotransmitter, glycine. Application of the glycine receptor antagonist, strychnine, alters the non-monotonic portion of the rate-intensity function at doses which do not alter spontaneous activity or near-threshold tone-evoked responses. These neurons are also sensitive to GABA and the GABAB agonist, (-)-baclofen, but are insensitive to the GABAA antagonist, bicuculline. DCN neurons which display monotonic rate-intensity functions and temporal response properties different than those associated with fusiform cells are sensitive to bicuculline, (-)-baclofen, and GABA. These data suggest that a glycinergic input onto fusiform cells may control the non-monotonic nature of the response of these neurons near characteristic frequency and therefore may contribute significantly to the nature of the output of the DCN.

Acoustic Stimulation↗

Glycine response in isolated dorsal cochlear nucleus of C57BL/6J mouse.

Pharmacological properties of glycine (Gly)-induced Cl- current (ICl) in the dorsal cochlear nucleus (DCN) neurons acutely dissociated from C57BL/6J mouse were investigated in the whole-cell configuration of the patch-clamp technique. Gly-induced ICl increased in a sigmoidal manner with higher Gly concentrations. Strychnine blocked the Gly response competitively at low and non-competitively at high concentrations. Both glutamate (Glu) and N-methyl-D-aspartate (NMDA) responses were augmented by adding 10(-6) M Gly, at which concentration Gly did not induce any ICl. This facilitation was not affected by strychnine. Our results clearly show the existence of strychnine-sensitive and -insensitive glycine receptors in the DCN neurons.

Animals↗

Tonotopic maps obtained from the surface of the dorsal cochlear nucleus of the hamster and rat.

Tonotopic organization was mapped over the surface of the dorsal cochlear nucleus (DCN) of the Syrian golden hamster and albino rat. The purpose of this study was to describe comparative similarities and differences in fine map features that exist between these two species, and to differentiate features which show a high degree of constancy from those which show significant variations across individuals of the same species. In general, the tonotopic organization seen in both species was characterized by a mediolateral gradient in which high CFs were located medially and low CFs laterally. Maps within each species displayed a high degree of constancy both in the slopes of the gradient as well as in the preferred rostrocaudal orientation of isofrequency contours. However, between species significant differences were seen in the slope of the CF gradient. In the rat, CFs declined toward the lateral extremity at a rate which was nearly twice that seen in the hamster, despite the fact that there were no apparent differences in the width of the DCN in these two species. The precise configuration of areas subtending selected frequency ranges also showed considerable individual variation and defined a 'microstructure' of tonotopic organization that was unique for each animal. The implications of these findings on concepts of DCN development and modes of innervation by the auditory nerve are discussed.

Acoustic Stimulation↗

Dynamic range of neural rate responses in the ventral cochlear nucleus of awake cats.

1. Response thresholds and dynamic range properties of neurons in the ventral cochlear nucleus (VCN) of awake cats were measured by fitting a computational model to rate-level functions for best frequency (BF) tone bursts and for bursts of broad-band noise. Dynamic range measurements were performed in quiet and in the presence of continuous background noise. 2. The sample of neurons obtained in the VCN of awake cats exhibited a variety of peristimulus histograms (PSTHs) and thresholds. All PSTH response types previously described in the VCN of anesthetized cats were found in awake cats. The lowest thresholds for neural responses were observed at sound pressure levels that were equivalent to behavioral thresholds of absolute auditory sensitivity. 3. When responses to BF tones or bursts of broad-band noise were recorded in quiet backgrounds, the dynamic range properties of most units in the VCN of awake cats were not significantly different from dynamic range properties of auditory nerve fibers (ANFs) in anesthetized cats or VCN units in decerebrate cats. All auditory units showed a larger dynamic range for noise bursts than for tone bursts, but VCN units with primary-like and onset PSTHs showed larger dynamic ranges for responses to noise bursts than that of ANFs and VCN chopper units. 4. When tests were performed in the presence of continuous noise, rate-level functions for BF tone bursts shifted to higher tone levels and showed a more compressed range of driven rates in comparison with data obtained in quiet. Compression of the rate-level function in noise resulted from an increase in driven rate at low tone levels and a decrease in rate at high tone levels. These changes in the rate-level function suggest that noise may reduce the range of BF tone levels that are potentially encoded by a unit's rate responses. By exhibiting larger shifts and less compression in background noise, VCN units in awake cats better preserved the dynamic range of their rate responses to BF tones than ANFs in anesthetized cats or VCN units in decerebrate cats. 5. Rate-level functions were obtained from a small sample of VCN units not only with the cat performing the behavioral task but also with the cat awake and sitting quietly in the testing apparatus. No differences in noise-induced shift or compression were noted between the two testing conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Membrane properties and discharge characteristics of guinea pig dorsal cochlear nucleus neurons studied in vitro.

Intracellular recordings were made from neurons of the guinea pig dorsal cochlear nucleus in an in vitro brain slice preparation. The membrane properties of the cells were studied, and the membrane potentials were manipulated by current injection to determine how intrinsic conductances might alter the cell discharge patterns. Eleven cells were marked with Lucifer yellow. Ten of these cells were identified as the large pyramidal cells of layer 2 of this nucleus, and 1 cell was identified as a "vertical" cell in layer 3. Two kinds of action potentials were observed: simple spikes and complex spikes. This report discusses only cells with simple spikes. Simple spiking cells (60/72 recorded cells; all stained cells were simple spiking cells) discharged in a regular fashion with depolarization, and had linear frequency-current relationships up to 2 nA with a mean slope of 116 Hz/nA. The discharge rate was approximately constant throughout the current pulse. Responses of simple spiking cells to depolarizing current steps superimposed on a steady-state membrane hyperpolarization were studied. When the membrane has been held hyperpolarized, small current pulses produce a long-latency regular train of action potentials. Larger current pulses superimposed on membrane hyperpolarization can produce a short-latency action potential followed by a long silent interval (i.e., a long first interspike interval), and finally a regular train of spikes. It is concluded that the membrane conductances of DCN pyramidal cells are capable of generating at least 3 discharge patterns (regular firing, long first spike latency, and long first interspike interval) depending on the state of the membrane potential prior to a depolarizing current step. These responses are similar to the "chopper," "buildup," and "pauser" discharge patterns reported for these cells in vivo in response to tone bursts. The modulation of the intrinsic membrane conductances by membrane polarization and the possible contribution of these conductances to the generation of DCN discharge patterns provide new insights into the mechanisms underlying the responses of DCN cells to acoustic stimuli.

Animals↗

A computational model for signal processing by the dorsal cochlear nucleus. II. Responses to broadband and notch noise.

In a previous paper a computational model was developed which was shown to account for most of the essential features of the variety of experimentally observed response maps of type-IV cells in the dorsal cochlear nucleus to pure tones. In the present study, the responses of the same model DCN to broadband noise and notch noise are investigated. It is shown that the previous model qualitatively accounts for the observed responses to these more complex sounds. Predictions of the model for inverted notches and for the behavior of type-IV cell output as notch center is varied for different amplitudes are presented. It is shown that the model is suitable for feature detection of auditory signals and an expansion is given as to how this ability arises from the properties of the stellate, type-II, and type-IV cells and the variations in the connectional patterns that were previously shown to account for the response patterns of type-IV cells to pure tones.

Auditory Perception↗

Phoneme recognition by deaf individuals using the multichannel nucleus cochlear implant.

Experiments have been carried out to determine which cues are used in phoneme identification by deaf individuals using a cochlear implant. Five deaf individuals with a Nucleus 22-channel cochlear implant were tested with open set speech audiometry in free field without lipreading. Speech material consisted of lists of Dutch words of the Consonant-Vowel-Consonant type (CVC-words). Word scores ranged from 0 to 22%, phoneme scores from 11 to 54%. For each subject the responses to the initial consonant, the vowel and the final consonant were entered into separate confusion matrices. Kruskal analysis, which provided a geometric representation of these confusions, showed that in the recognition of consonants the feature of voicing is all important. Vowels were identified on the basis of the frequencies of the first and second formants. In one subject the electrode array could only partially be inserted into the cochlea, leaving roughly half the second formant area of the electrode array outside the cochlea. For this subject vowel identification was based upon the first formant and vowel duration; there was no contribution of second formant information to vowel identification. Compressing the first and second formant frequency to the limited intracochlear array did not enhance transmission of second formant information and did not improve performance. The basic findings for consonant and vowel recognition could be explained by the speech coding strategy of the Nucleus speech processor in which voicing determines stimulus periodicity and formant frequencies determine channel selection. Kruskal analysis of phoneme confusions may aid in programming and evaluating the performance of the Nucleus cochlear implant.

Adult↗