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Periaqueductal gray influence on anteroventral cochlear nucleus unitary activity and naloxone effects.

The effect of periaqueductal gray (PAG) electrical stimulation on the response properties of auditory and 'spontaneously' firing units (abolished when the cochlea is destroyed) in the anteroventral cochlear nucleus (AVCN) was explored using extracellular recordings in acute guinea-pigs. Significant increases and decreases in firing rate were detected in both neuronal groups: only 4% of the sound-responding units were insensitive to PAG stimulation while the 'spontaneous' units showed significantly smaller changes in firing rate in response to PAG stimulation. The auditory AVCN neurons were categorized both by their sound post stimulus time (PST) histograms at their characteristic frequency (CF) and the changes in the probability of discharge after PAG stimulation while the tone burst was maintained constant. PAG was implicated in pain input modulation through enkephalin actions. Because enkephalins have been also observed at the CN level, a pharmacological approach administering naloxone was carried out. We observed that 1) naloxone abolished the unit discharge shifts observed after PAG stimulation and 2) when the drug was injected without PAG stimulation, it produced changes in the firing, increasing or decreasing, and shifts in the probability of discharge versus time, even in cases in which the firing rate was not altered. An involvement of the auditory efferent pathways to CN is postulated and a possible enkephalinergic factor is suggested as a modulator of the auditory input at this level. The probability of discharge observed in the PSTH at the AVCN is dependent on the auditory input plus the central efferent action to its neurons.

Acoustic Stimulation↗

The polypeptide PEP-19 is a marker for Purkinje neurons in cerebellar cortex and cartwheel neurons in the dorsal cochlear nucleus.

This light and electron microscopic immunocytochemical study shows that the polypeptide PEP-19, a presumptive calcium binding protein specific to the nervous system, represents an excellent marker for cerebellar Purkinje cells and dorsal cochlear nucleus (DCoN) cartwheel cells. The polypeptide clearly reveals the entire populations of both types of neurons, including their complete dendritic and axonal arborizations. Other PEP-19 containing neurons in the two regions display weak immunoreactivity restricted to the cell body or to cell body and principal dendrites. Electron microscopic localization of PEP-19-like immunoreactivity reveals similarities between this polypeptide, parvalbumin, and a 28K vitamin D-dependent calcium binding protein. However, calmodulin, which is expressed in both Purkinje and granule cells, may differ from PEP-19. Similarities between the organization of the cerebellar cortex and the DCoN superficial layers have been known for some time, with several types of neurons in one system having their presumed homologue in the other. These data provide further support for the proposed structural and functional homology between Purkinje and cartwheel neurons, and establishes PEP-19 as a useful marker for examining degeneration of these two neuronal populations in murine cerebellar mutants.

Animals↗

Spatial response profiles of posteroventral cochlear nucleus neurons and auditory-nerve fibers in unanesthetized decerebrate cats: response to pure tones.

Encoding of 1- and 5-kHz pure tones by auditory-nerve (AN) fibers and choppers of the posteroventral cochlear nucleus (PVCN) was investigated. Neuronal responses were analyzed as the discharge rate, rate change, and the mean and standard deviation (or sigma) of spike counts. The major findings are: (1) Sideband inhibitory areas were observed in spatial profiles of rate changes of PVCN choppers whereas they were absent in those of AN fibers; (2) spatial profiles of rate changes and mean discharge rates of PVCN choppers were sharper than those of high spontaneous-rate (HSR) AN fibers and were comparable to those of low and medium SR (LMSR) AN fibers for 1 kHz at 50 and 70 dB SPL re: 20 microPa; (3) to 5 kHz, 30 dB SPL, PVCN choppers were strongly driven comparable to HSR AN fibers whereas LMSR AN fibers were weakly driven (implying higher thresholds); (4) PVCN choppers exhibited higher maximum discharge rates (300-600 spikes/s) than either LMSR AN fibers (200-250 spikes/s) or HSR AN fibers (150-250 spikes/s); (5) mean-to-sigma ratios of PVCN choppers, particularly at 70 dB SPL, were much higher than those of LMSR or HSR AN fibers; (6) rate-change profiles of LMSR AN fibers were distinct from those of HSR AN fibers, more conspicuously for 1 kHz than for 5 kHz; (7) the neural response profiles to 5 kHz were sharper than those to 1 kHz; and (8) 45% of PVCN choppers in the present study exhibited SR greater than 20 spikes/s whereas only 11%-12% of AVCN choppers in previous studies of anesthetized cats exhibited the same SR, which may represent an effect of anesthesia. The observations support a hypothesis that the transformation of the discharge-rate signal from AN fibers to PVCN choppers leads to an amplification of the mean discharge-rate signal with an increase in the signal-to-noise ratio. The observations suggest that PVCN choppers can encode pure-tone frequency in a spatial profile more accurately than HSR or LMSR AN fibers. The present data on AN and PVCN spatial profiles should be valuable to CN modeling studies by providing the input to the CN and the output of a class of physiologically characterized CN neurons for an identical set of stimuli.

Animals↗

Responses of single units in the cat cochlear nucleus to sinusoidal amplitude modulation of tones and noise: linearity and relation to speech perception.

Responses to the sinusoidal modulation envelopes of amplitude-modulated tonend noise carriers were recorded from single units in the cochlear nucleus of the cat. The unit discharges were synchronized to the peaks of the modulation envelope. Population-averaged firing rate were independent of the modulation index of the stimulus. Temporal firing patterns, as represented by the shapes and magnitudes of modulation-cycle histograms, were strongly dependent on stimulus intesity and modulation index. Nonlinear nonsinusoidal responses to sinusoidal modulation envelopes were observed, but only at high values of sound intensity. These and other results are discussed in the context of psychological studies concerning the perception of speech information.

Acoustic Stimulation↗

Spiral ganglion cell endings in the cochlear nucleus of young and old rats.

The spiral ganglion cells (SGCs) forming the auditory nerve have been shown to degenerate with age in both human and animal models, presumably resulting in post-synaptic sites in the cochlear nucleus (CN) that have lost their inputs. The present study examined the morphological changes in the surviving SGC endings in the CN of aged animals. The auditory nerves of 2-3 MO and 25-26 MO male, Fisher 344 rats were anterogradely labeled with horseradish peroxidase and the CN prepared histochemically. This resulted in Golgi-like labeling of afferent fibers and their terminals. All endings within each section were drawn and the area and number of components per ending were measured. Young and old animals both had about the same proportion of "simple", "string" and "complex" endings within the ventral CN, with complex endings being predominant in both age groups. The area of many complex endings was greater in the old animals with some endings being twice as large as any seen in young animals. There was no evidence of smaller endings in the old animals, suggesting that endings are not shrinking with age. A comparison of the number of components per complex ending revealed significantly more complexity in the endings of aged animals. Following the degeneration of SGCs it seems likely that the remaining cells, by increasing the area and altering the shape of their central terminals, may cover some of the post-synaptic sites made available by degenerated endings in aged animals.

Aging↗

Comparison of procedures for obtaining thresholds and maximum acceptable loudness levels with the nucleus cochlear implant system.

Two stimulus paradigms and two presentation methods were combined to form three procedures (keyboard, knob, and ascending loudness judgments with knob [ALJK]) to obtain detection thresholds and maximum acceptable loudness levels (MALs) from 11 adults with the Nucleus cochlear implant. Thresholds at which subjects correctly counted the number of stimulus bursts also were obtained. Keyboard detection thresholds were higher (Scheffé, p = .01) than knob and ALJK detection thresholds. Counted thresholds were obtained most efficiently by using keyboard detection thresholds as the initial level for testing. Keyboard MALs were highest, knob MALs intermediate, and ALJK MALs lowest (Scheffé, p = .001). MALs were obtained most efficiently with the ALJK procedure. Implications of these results for clinical practice are discussed.

Adult↗

Modelling the sensitivity of cells in the anteroventral cochlear nucleus to spatiotemporal discharge patterns.

This study investigates a potential mechanism for the processing of acoustic information that is encoded in the spatiotemporal discharge patterns of auditory nerve (AN) fibres. Recent physiological evidence has demonstrated that some low-frequency cells in the anteroventral cochlear nucleus (AVCN) are sensitive to manipulations of the phase spectrum of complex sounds (Carney 1990b). These manipulations result in systematic changes in the spatiotemporal discharge patterns across groups of low-frequency AN fibres having different characteristic frequencies (CFS). One interpretation of these results is that these neurons in the AVCN receive convergent inputs from AN fibres with different CFS, and that the cells perform a coincidence detection or cross-correlation upon their inputs. This report presents a model that was developed to test this interpretation.

Acoustic Stimulation↗

Encoding of amplitude modulation in the gerbil cochlear nucleus: II. Possible neural mechanisms.

Rapid changes in sound amplitude--amplitude modulation (AM)--comprise an important feature of biologically-relevant sounds, including speech. In the companion paper, a hierarchy of enhancement for AM processing was demonstrated for unit types of the gerbil ventral cochlear nucleus (VCN) [Frisina, et al., Hear. Res. 44, 1990]. In the present report additional neurophysiological findings are presented as an initial test of alternative hypotheses of how VCN unit types amplify or enhance AM information, and how they accomplish this over a wide intensity range. These hypotheses invoke mechanisms such as off-CF excitatory or inhibitory inputs, input from high-threshold auditory-nerve fibers, amplification of residual AM responses of auditory-nerve fibers at high intensities, or post-synaptic cell feedback. From consideration of VCN unit response properties such as onset and steady-state rate-intensity functions, pure-tone tuning, and non-CF responses to AM, it is concluded that: Off-CF excitatory inputs do not play a significant role in VCN AM encoding; Off-CF inhibitory inputs could work in conjunction with one or more of the other proposed mechanisms to account for differential enhancement of AM by VCN neurons.

Action Potentials↗

Influence of neonatal cochlear removal on the development of mouse cochlear nucleus. III. Its efferent projections to inferior colliculus.

In order to determine the transneuronal developmental influences of auditory deafferentation, the right cochleas, with the first order spiral ganglion neurons, were removed in 6-day-old mice to eliminate all peripheral input to the right cochlear nucleus (CN). At 45 days, some of the efferent projections of right CN in these unilaterally lesioned mice and their unoperated controls were identified by retrograde transport of horseradish peroxidase from the contralateral (left) inferior colliculus (IC). In both groups of animals, reaction product was observed in neurons of the right CN, contralateral to the injection, and no labeling was seen in the ipsilateral left CN in either group. Contralaterally labeled were the fusiform cells of dorsal CN, the globular cells of ventral CN, and neurons within the nucleus of the intermediate acoustic stria. Quantification revealed significantly fewer fusiform and globular cells labeled in the deafferented CN, whereas the number of labeled acoustic stria neurons was the same in both groups. Although the deafferented CN had 65.4% fewer labeled neurons, the proportions projecting to IC were similar in the two groups, 7.8%. Because of this significant reduction in the number of deafferented CN neurons projecting to the contralateral IC, it was concluded that the transneuronal effects of deafferentation would be to deprive or deafferent developing neurons within the higher auditory brainstem nuclei.

Animals↗

Neural correlations in the dorsal cochlear nucleus: pairs of units with similar response properties.

1. Cross-correlation analysis of simultaneously recorded spike trains can be used to gain insight into functional interactions among neurons. In this paper, we report on cross-correlation analysis of neuron pairs in the dorsal cochlear nucleus (DCN) of the cat. Neuron pairs were isolated with two independent electrodes, which allow systematic study of the effects on correlation of distances between units and differences in their best frequencies (BFs). The data in this paper were obtained from 51 pairs consisting of two neurons of the same type. 2. Cross-correlograms were obtained for 35 pairs composed of type IV units, which are recorded from the principal cells of the DCN. Pairs of type IV units with correlated activities give cross-correlograms with increased correlation near zero delay. This feature is called a central mound (CM) and most likely results from shared excitatory or shared inhibitory inputs. 3. Records of spontaneous activity were obtained from 31 pairs of type IV units. Six of these pairs have correlated spontaneous activities. All six pairs have BFs that differ by less than 0.2 octaves. The shared input inducing these correlations must be a spontaneously active and tonotopically organized projection, like the auditory nerve. Type II units, thought to be DCN inhibitory interneurons that project to type IV units, are not spontaneously active, and thus cannot be the cause of correlated spontaneous activity. Similarly, cochlear granule cells, whose axons project orthogonally to the tonotopic sheets of DCN, cannot be the cause of correlated spontaneous activity because their projection is not confined tonotopically. 4. Stimulus-driven activities were studied for 12 type IV pairs that have uncorrelated spontaneous activities. Five of these pairs have correlated driven activities, with CMs whose sizes depend on the frequency and sound level of the acoustic stimulus. A frequency vs. sound level correlation response map shows the V-shaped tuning properties of the correlation-inducing mechanism. The properties of stimulus-driven correlation in these type IV pairs are consistent with the hypothesis that the correlation is induced by shared input from DCN type II units, although this is not the only possibility. 5. All six type IV pairs with correlated spontaneous activities have correlated driven activities. In five of these pairs, the degree of correlation decreases from its value with spontaneous activity when a low-level acoustic stimulus is applied. Three of these five pairs were tested at higher stimulus levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Effects of the murine mutation 'nervous' on neurons in cerebellum and dorsal cochlear nucleus.

'Nervous' mutant mice are presently available on two different genetic background strains which are derived from out-breeding of the original BALB/cGr mutant stock. Light and electron microscopic studies of these mutants demonstrate that cerebellar Purkinje cells and cartwheel neurons of the dorsal cochlear nucleus (DCoN) show similar, albeit not identical, cytoplasmic and mitochondrial alterations in both background strains. In the cerebellar cortex, all Purkinje cell perikarya developed a varying number of enlarged and rounded mitochondria, as previously described. Extensive changes were observed in various components of the mitochondrial matrix. As cellular degeneration proceeded, reduction, fragmentation and dilation of cisterns of endoplasmic reticulum and the Golgi apparatus were evident. Some of the mitochondria underwent a peculiar type of degeneration, i.e. the outer membrane partially or completely dissolved, occasionally accompanied by focal interruptions of the inner membrane. In older adult mutants only 10% of cerebellar Purkinje cells rehained. The few surviving cells displayed varying states, ranging from essentially normal ultrastructure to electron-dense condensation. Many of these cells, in both strains, continued to display greatly enlarged, rounded mitochondrial profiles, indicating a change in the expression of the gene defect resulting from genetic contamination. Criteria for the identification of neuronal cell classes in layers 1 and 2 of murine DCoN were established. Cartwheel neurons in the mutant DCoN presented alterations similar to those observed in cerebellar Purkinje cells. The characteristic mitochondrial anomaly developed and proceeded in cartwheel neurons within a comparable time frame. The vast majority of affected cartwheel cells did not undergo degeneration, however, but continued to possess altered mitochondria into adulthood. The differences between normal and mutant mitochondria in Purkinje and cartwheel were quantified by morphometric analyses. Our findings lend support to the notion of a homology between cerebellar Purkinje cells and DCoN cartwheel cells. These cells represent major elements in two similar spatially related circuits, and share several genetic, structural and neurochemical properties. It is therefore proposed that these two cell populations are derived from closely related precursor cells.

Aging↗

Analysis of temporal discharge characteristics of dorsal cochlear nucleus neurons of unanesthetized decerebrate cats.

1. We examined the mean and standard deviation (SD) of interspike intervals (ISI) and the coefficient of variation (CV, the ratio of SD of ISI to mean ISI) of ISIs versus time to study discharge regularity of units in the dorsal cochlear nucleus (DCN) of decerebrate unanesthetized cats. The units were characterized by the use of both poststimulus time histograms (PSTH) and excitatory-inhibitory area (EI-area) schemes. We present results of a systematic examination of all of 87 DCN pause-build units recorded in this study. In addition, we present examples of chopper subtypes of the DCN. 2. A major finding of this study is that a majority of the pause-build units in the present sample exhibited regular discharges in response to short (50 ms) tone bursts at characteristic frequency (CF), as revealed by CVs less than 0.5. A predominant portion of pause-build units (80% of 44 units with sufficient number of spikes for CV analysis) exhibited mean CVs less than 0.5 in the 20- to 39.9-ms time window in response to 50-ms tone burst at CF at 60 dB SPL re 20 microPa; 39% of the 44 units exhibited highly regular discharges (mean CV less than 0.35). During the onset (2-14.9 ms) time window, 77% (of 53 units with sufficient number of spikes for CV analysis) of the units had mean CVs less than 0.5, and 55% were less than 0.35. 3. In our sample of 87 DCN pause-build units, 59% had spontaneous rates (SR) greater than 15 spikes/s. The pause-build units of the present sample were distributed across four different EI-area types: III (51%), I/III (25%), II (15%), or IV (9%). In the 20- to 39.9-ms time window, the pause-build units with mean CVs less than 0.35 were exclusively of types III and I/III. All of the above EI-area types were represented in the lowest CV group for the 2- to 14.9-ms window. 4. The mean ISIs of DCN pause-build units typically showed a decrease during the first 20-25 ms of the response to 50-ms CF tone bursts, and stable mean ISIs in the latter half, when off-discharges were absent. In the presence of off-discharges, the mean ISIs decreased further in the last 5-10 ms of the response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Stimulus dependent neural correlation: an example from the cochlear nucleus.

Results of several recent cross-correlation studies have been interpreted in terms of "neuronal plasticity" and "stimulus dependent wiring diagrams" produced by presumed dynamic neural reorganization mechanisms. Presented here are examples of stimulus-dependent cross-correlograms observed in a pair of type IV units recorded in the dorsal cochlear nucleus (DCN). The interpretation of these correlation data is based on current hypotheses of DCN circuitry. It is suggested that plasticity mechanisms are not responsible for these stimulus-dependent correlations. A more likely mechanism is one that allows various portions of a hard wired neural circuit to be selectively activated by the stimuli.

Acoustic Stimulation↗

The effects of auditory deprivation on morphological maturation of the ventral cochlear nucleus.

The volumes of the auditory brainstem nuclei and age-related auditory brainstem response (ABR) thresholds were analyzed in homozygote (je/je) and heterozygote (je/+) jerker mutant mice. Altogether 97 mice were used in the study. Je/je mice never develop any hearing. The dorsal (DCN) and ventral (VCN) cochlear nuclei were found to have stopped their growth at 56 days after birth. In je/+ mutants, ABR thresholds remained normal or near-normal for 3-6 months, whereas VCN and DCN volumes remained unchanged at least after 56 days after birth. There is no significant difference in DCN volume in je/je and je/+ mice. However, the VCN volume and the cross-sectional area of globular cells were both significantly larger in je/+ than in je/je mice (P less than 0.01). These findings show that auditory deprivation during the maturation of hearing in je/je mutants causes an incomplete maturation of only the ventral cochlear nucleus.

Animals↗

Superior paraolivary nucleus in the pigmented guinea pig: separate classes of neurons project to the inferior colliculus and the cochlear nucleus.

The superior paraolivary nucleus is a large component of the superior olivary complex in rodents and a major source of input to the inferior colliculi and the cochlear nuclei. In the present study, retrograde transport of the fluorescent tracers Fluoro-Gold, Fluoro-Ruby (tetramethyl rhodamine conjugated to dextran), fluorescein-coated microspheres, and Fast Blue were used to reveal the morphology and collateral projection patterns of cells in the superior paraolivary nucleus. The ascending projections to the inferior colliculus from the superior paraolivary nucleus arise mainly from round, multipolar cells, including large cells that project exclusively to the inferior colliculi and not to the cochlear nuclei. Projections to the ipsilateral and contralateral inferior colliculi arise from cells with similar morphology and, in fact, many of the cells that project contralaterally project ipsilaterally as well. Projections to the ipsilateral and contralateral cochlear nuclei arise primarily from cells that do not have collicular projections. On average, the somas of these cells are significantly smaller and more elongated than those that project to the inferior colliculi. Overlap between these ascending and descending systems is restricted to a small percentage of cells that send collateral projections to both the ipsilateral cochlear nucleus and the ipsilateral inferior colliculus. These cells are small and moderately elongated. Thus the ascending and descending projections examined here arise largely from different cells that belong to different morphological classes.

Animals↗

Morphometric analysis of developing neuronal geometry in the dorsal cochlear nucleus of the hamster.

Since the shape of a cell's dendritic field and the distribution of its input determine the information that a cell receives and transmits, it is important to ascertain how the spatial relations between axonal arbors and dendritic fields develop. This study investigates the development of the dendritic fields of fusiform cells in the dorsal cochlear nucleus. Golgi-impregnated cells from postnatal day 10, 15, 25, 45 and 60+ hamsters were reconstructed. The computerized morphometric system used analyzed cells in the plane of section and also allowed rotation to and analysis in other specified planes, such as that parallel to the terminal arbors of the cochlear nerve fibers. The results suggest that the apical dendritic fields are oriented parallel to the axis of cochleotopic organization and that this orientation develops gradually after birth. Dendritic growth is the result of addition of new dendritic branches. The angles between branches also change and were analyzed by viewing the dendritic fields in different planes. This revealed that some preferential expansion of the apical dendritic field in the plane parallel to the cochlear projection planes is the result of increased angles between branches in that plane. Thus, dendritic growth via the addition of branches and the 'fanning-out' of existing branches underlie the development of oriented dendritic fields.

Animals↗

[Interaction between auditory and trigeminal afferent volleys in the dorsal cochlear nucleus of rats].

In chloralose anaesthetized rats preliminary electrical stimulation of the second branch of the trigeminal nerve diminished the amplitude of all component of the evoked potential produced by click, when the interval between conditioning and testing stimuli was up to 40 ms. Only late negative-positive component of the evoked potential was depressed when the interval between the stimuli was increased. The conclusion is made that the afferent inflow to the dorsal cochlear nucleus is controlled by peripheral mechanisms changing the sensory input and by central descending inhibitory influences on the nucleus.

Animals↗