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Neural response to very low-frequency sound in the avian cochlear nucleus.

Recordings were made in the chick cochlear nucleus from neurons that are sensitive to very low frequency sound. The tuning, discharge rate response and phase-locking properties of these units are described in detail. The principal conclusions are: 1. Low frequency (LF) units respond to sound frequencies between 10-800 Hz. Best thresholds average 60 dB SPL, and are occasionally as low as 40 dB SPL. While behavioral thresholds in this frequency range are not available for the domestic chick, these values are in good agreement with the pigeon behavioral audiogram (Kreithen and Quine 1979). 2. About 60% of the unit population displays tuning curves resembling low-pass filter functions with corner frequencies between 50-250 Hz. The remaining units have broad band-pass tuning curves. Best frequencies range from 50-300 Hz. 3. Spontaneous discharge rate was analyzed quantitatively for LF units recorded from nucleus angularis. The distribution of spontaneous rates for LF units is similar to that seen from higher CF units (300-5000 Hz) found in the same nucleus. However, the spontaneous firing of LF units is considerably more regular than that of their higher CF counterparts. 4. Low frequency units with low spontaneous rates (SR's less than 40 spikes/s) show large driven rate increases and usually saturate by discharging once or twice per stimulus cycle. Higher SR units often show no driven rate increases. 5. All LF units show strong phase-locking at all excitatory stimulus frequencies. Vector strengths as high as 0.98 have been observed at moderate sound levels. 6. The preferred phase of discharge (relative to the sound stimulus) increases with stimulus frequency in a nearly linear manner. This is consistent with the LF units being stimulated by a traveling wave. The slope of these phase-frequency relationships provides an estimate of traveling wave delay. These delays average 7.2 ms, longer than those seen for higher CF auditory brainstem units. These observations suggest that the peripheral site of low frequency sensitivity is the very distal region of the basilar papilla, an area whose morphology differs significantly from the rest of the chick basilar papilla. 7. LF units are described whose response to sound is inhibitory at frequencies above 50 Hz.

Acoustic Stimulation↗

Activation of cells of cochlear nucleus by electrical stimulation of lateral hypothalamus.

Effects of electrical stimulation of the lateral hypothalamus (HS) were examined in 67 cells of the dorsal or ventral cochlear nucleus. Both short latency activity in the 10-20 ms post-stimulus period and late activity in the > 20 ms post-stimulus period were elicited in response to HS. A greater percentage of units exhibited the short latency response in dorsal (89%) than ventral (68%) cochlear nucleus. It was not previously recognized that stimulation of the hypothalamus could elicit increases in spike activity in this auditory relay nucleus. The hypothalamus is known to play a role in visceral-emotional functions, including feeding, fleeing, fighting and reproductive behavior. These results suggest a means by which neural activities supporting these functions could influence acoustic relay transmissions.

Animals↗

Unit activity to click CS changes in dorsal cochlear nucleus after conditioning.

Recordings were made of single unit activity (n = 360 units) from the dorsal cochlear nucleus of cats. Different patterns of activity were elicited by acoustic stimuli before and after Pavlovian conditioning. The peak response to a forward paired click conditioned stimulus (CS) increased whereas that to a backward paired hiss discriminative stimulus (DS) did not. The percentage of units responding to the CS increased from 34% to 46% after conditioning. The findings do not support the widely accepted hypothesis that learning has no effect on transmission through the first brain stem relay of the auditory system and indicate, instead, that the cochlear nucleus can participate in complex adaptive acoustic signal processing.

Acoustic Stimulation↗

Pyramidal neurones of the dorsal cochlear nucleus: a Golgi and computer reconstruction study in cat.

The main projection neurones of the dorsal cochlear nucleus, termed pyramidal, bipolar or fusiform cells, have an apical dendritic arbor approaching the ependymal surface of the nucleus and a basal arbor oppositely directed. In Golgi-Del Rio-Hortega material these neurones were studied, with the light microscope, in nonconventional planes of sectioning oriented across or parallel to the main axis of the elongated nucleus. The pyramidal neurones were seen to be flattened across this axis. The size, shape and orientation of 21 cells from six blocks were studied in detail with computer-aided graphic reconstructions including stereo views. Camera lucida drawings of each cell (usually from several sections) were digitized to obtain x and y coordinates while z coordinates (depths in the tissue) were read from the fine focus knob during microscopy and typed interactively during digitization. The z values were corrected for the effects of refractive index differences in the optical system. Since it was the aim of this study to focus on some fundamental principles of structure and arrangement of pyramidal cells in the dorsal cochlear nucleus rather than on topographic variations, only the middle, regularly built part of the nucleus was examined. Towards the ends of the nucleus the architecture is less regular and will require separate analysis. Measurements of arbor and total cell height and of dendritic length are given. The height of the apical and basal arbor in individual cells showed considerable reciprocity. The total dendritic length was up to 8300 micron (average 6536 micron). The basal arbors always proved to be conspicuously flattened; roughly, the width varied between about 300 and 700 micron (average 489 micron) and the thickness between 65 and 105 micron (average 80 micron). The apical arbors were also often flattened but much less and with a greater variability than the basal arbors (average width 319 micron, thickness 115 micron). The two arbors of individual cells were practically coplanar, the arbor planes showing only moderate angularity (bend) and/or torsion relative to each other (angularity maximum 10 degrees, average 5 degrees; torsion maximum 18 degrees, average 6 degrees). The mutual orientation of cells from the same block was examined. The planes through the basal arbors proved to be very parallel, the differences in orientation angles being between 10 and 0 degrees with rare exceptions. Clearly flattened, apical arbors showed a somewhat greater spread.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Age-related increases in calcium-binding protein immunoreactivity in the cochlear nucleus of hearing impaired C57BL/6J mice.

Aging C57BL/6J (C57) mice (1-30 months old), were used to study calcium-binding protein immunoreactivity (parvalbumin, calbindin and calretinin) in the cochlear nucleus. A quantitative stereological method, the optical fractionator was used to determine the total number of neurons, and the total number of immunostained neurons in the posteroventral- and dorsal cochlear nuclei (PVCN and DCN). A statistically significant age-related decrease of the total number of neurons was found in the PVCN and DCN using Nissl staining. In the DCN, an age-related increase in the total number of parvalbumin-positive neurons was found, while no changes in the total number of calbindin or calretinin positive neurons were demonstrated. In the PVCN, the total number of parvalbumin, calbindin, or calretinin positive neurons remained stable with increasing age. The percentage of parvalbumin, calbindin, and calretinin positive neurons significantly increased in the DCN, and the percentage of parvalbumin and calbindin-positive neurons increased in the PVCN. These findings imply that there is a relative up-regulation of calcium-binding proteins in neurons that had not previously expressed these proteins. This plastic response in the profoundly hearing impaired C57 mouse may be a survival strategy for cochlear nucleus neurons.

Adaptation, Physiological↗

The time course of recovery from suppression and facilitation from single units in the mammalian cochlear nucleus.

The responses to two identical, consecutive pure tone stimuli with varying inter-stimulus intervals (delta ts) were measured for 89 neurons in the cochlear nucleus of the anaesthetised guinea pig. We observed two main effects; either a decrease (suppression) or an increase (facilitation) in response to the second tone followed by an exponential recovery. Response behaviour correlated with the unit type; primary-like, primary-like with notch and transient-chopper units showed a recovery from suppression that was very similar to that already reported in the auditory nerve. For chopper units the strength of the adaptation was correlated with the units regularity of spike discharge; sustained chopper (CS) units showed less suppression than transient choppers. Onset units showed complete suppression at short delta ts. Pause/Build (PB) units responded with increased activity to the second tone. In contrast to previous studies in the cochlear nucleus the recovery from suppression or facilitation was well described by a single exponential function, enabling us to define a recovery time constant and a maximum suppression/facilitation. There appeared to be a hierarchy in the time constant of recovery with PB and CS units showing the longest recovery times and onset units showing the shortest.

Animals↗

Temporal and mean rate discharge patterns of single units in the dorsal cochlear nucleus of the anesthetized guinea pig.

1. We examined the temporal and mean rate discharge characteristics of 514 single units recorded extracellularly from the dorsal cochlear nucleus (DCN) of anesthetized guinea pigs. A mean rate response area (receptive field) was measured for the majority of units in this study. Each response area was placed in one of seven categories (type I to type V and the intermediate types I/III and IV-T) as defined by previous workers. The shape of the best frequency (BF) rate-level function has been used to aid in the distinction between type IV and type IV-T units, and the classification of type II units is based on their relative response to noise and tone bursts. 2. The threshold of single units was normalized to the cochlear action potential (CAP) threshold (a negative relative threshold indicates that the unit's threshold was more sensitive than the corresponding CAP threshold). There were significant differences (P < 0.05; 1-way analysis of variance--Duncan test) between the mean relative thresholds of type IV units (-12 dB) and those of type I (-6.52 dB), type II (-3 dB), and type I/III units (-4.25 dB). There were also significant differences between the relative thresholds of types III and IV-T and those of types I/III and II. 3. Rate-level functions at a unit's BF were divided into groups according to shape and degree of nonmonotonicity. Six units responded with a decrease in firing rate at all suprathreshold sound levels. However, most units increased their discharge rate over approximately the first 20 dB above BF threshold. Units were further subdivided by the change in slope 20 dB above BF threshold. The majority of units (60%) showed monotonic increases in discharge rate with sound level: some rate-level functions clearly resembled the sloping saturation rate-level functions observed in intermediate-threshold auditory nerve fibers. An unexpected finding was the relatively large number of nonmonotonic rate-level functions (40%). Among a relatively homogenous group of projection neurons (predominantly type IV and pause/build units) with nonmonotonic rate-level functions, the range of "best intensities" (the sound level evoking the highest discharge rate) was < 50 dB. This range of best intensities is narrower than found in higher auditory nuclei. 4. Units were also classified by their temporal activity pattern in response to suprathreshold BF tones. The most common pattern identified is the pause/build pattern (n = 294). This temporal activity pattern has been associated with the principal output neuron of the DCN, the fusiform cell. Our definition of pause/build units includes units with an almost constant steady-state discharge rate. Nonmonotonic rate-level functions were observed in 42% (99 of 233) of pause/build units. A measure of discharge regularity (the SD of the interspike interval/mean interspike interval: coefficient of variation, CV) revealed that the majority (82%) of units classified as pause/build and with steady-state discharge rates > 75 spikes/s (n = 142) were characterized by regular discharge patterns (CV = 0.41 +/- 0.15, mean +/- SD). 5. Units characterized by chopper or onset-type discharges were the next most frequently encountered units. The chopper units (n = 75) showed a regular discharge (CV = 0.39 +/- 0.17) similar to that found in recordings from the ventral division of the cochlear nucleus (VCN). One difference between many chopper units in the DCN compared with those recorded in the VCN was the relatively high value (> 5 ms) of the mean interspike interval (and thus the low steady-state discharge rate). The majority (44 of 59; 75%) of chopper units had monotonic rate-level functions. Onset units (n = 47) may represent several response types, linked by the predominance of discharges in response to stimulus onset, and the majority of onset units reported here bear little resemblance to onset units recorded in the VCN of the guinea pig. Approximately 10% of units did not fit easily into any of th

Acoustic Stimulation↗

Divergent projections of physiologically characterized rat ventral cochlear nucleus neurons as shown by intra-axonal injection of horseradish peroxidase.

An attempt was made to correlate electrophysiological and morphological characteristics of rat ventral cochlear nucleus neurons. Their axonal course and their soma morphology were investigated using the intra-axonal horseradish peroxidase method. Prior to labeling, neurons were characterized by recording their response patterns to acoustic stimulation with pure tones. Three types of cells were found: Category I (37 neurons) exhibited "primarylike" responses and a spontaneous firing rate below 10 spikes/s. Category II (21 neurons) showed "on" responses and little spontaneous activity. Category III (9 neurons) had "primarylike" responses like neurons in category I. However, the spontaneous activity rate of these neurons was significantly higher (mean: 95 spikes/s). Among the response categories, the morphological characteristics differed in some prominent aspects. Within each category, however, the morphological properties were rather similar. All neurons in category I were globular/bushy cells located in the area of the entrance of the cochlear nerve. The axon of each cell coursed along the ventral acoustic stria and consistently innervated the lateral superior olive ipsilaterally, and the nucleus of the trapezoid body and the nucleus of the lateral lemniscus contralaterally. Some neurons also projected to periolivary nuclei ipsilaterally and contralaterally. Neurons in category II were located in the posteroventral cochlear nucleus and were presumably multipolar/stellate cells. Their axons coursed via the intermediate acoustic stria and innervated mainly contralateral periolivary regions as well as the contralateral nucleus of the lateral lemniscus. Ipsilaterally, the lateral superior olive and the superior periolivary nucleus were innervated by some of the category II neurons. Somata types of neurons in category III could not be identified morphologically, but somata were located in caudal parts of the posteroventral cochlear nucleus that correspond to the octopus cell area. Their axons coursed via the intermediate acoustic stria and innervated periolivary regions and the contralateral nucleus of the lateral lemniscus. Thus, their axonal distribution differed only slightly from neurons in category II. These data confirm and extend previous findings regarding the efferent connections of ventral cochlear neurons. They emphasize the complexity of the axonal projection patterns of single cochlear nucleus cells. Since two types of response patterns and three types of axonal projection patterns have been observed, there remains an ambiguous relation between response pattern and axonal projection site.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Distribution of gamma-aminobutyric acid, glycine, glutamate and aspartate in the cochlear nucleus of the rat.

The distributions of gamma-aminobutyric acid (GABA), glycine, glutamate and aspartate were measured in cochlear nuclei of two rats by quantitative histochemical mapping procedures. The levels and distributions in the two rats were comparable, and resembled those previously reported for cat cochlear nucleus. The results are consistent with a concept that these putative transmitter amino acids have similar levels and distributions in the cochlear nucleus among mammals.

Aminobutyrates↗

Spectral time-course analysis of firing patterns in the dorsal cochlear nucleus.

Many previous studies of central auditory neurons have involved independent analyses of spectral and temporal response properties. The spectral response analysis is useful for defining the frequency and intensity regions over which a neuron is excited or inhibited. However, the conventional spectral response analysis only defines this distribution for the synaptic polarity (excitation or inhibition) which dominates the duration of the response. PST histograms of dorsal cochlear nucleus neurons however, often exhibit both excitatory and inhibitory (i.e. pause) components. The distribution of these transient pause intervals may in turn be highly dependent on stimulus parameters suggesting that the spectral area of excitation and inhibition, when considered in terms of short time frames, may be time-dependent. We performed a temporal analysis of the spectral response areas of neurons in the rat dorsal cochlear nucleus and present here an example based on a neuron showing distinct pauser and buildup responses in its PST histograms. The resulting analysis yielded a time course of the spectral response area which indicates that the transient periods of inhibition may have the effect of narrowing the bandwidth of excitation during the early portion of stimulation. Possible implications of this time course are discussed in relation to the narrower tuning that cochlear nucleus neurons often display in response to frequency sweeps than to pure tones.

Acoustic Stimulation↗

Auditory brainstem of the ferret: early cessation of developmental sensitivity of neurons in the cochlear nucleus to removal of the cochlea.

The role of primary afferent innervation in the maintenance of neurons in the mammalian auditory system was assessed by performing unilateral removals of the cochlea in neonatal and mature ferrets of known birth dates. Removals were performed under steroid anesthesia and resulted in the complete destruction of the organ of Corti and the loss of at least 80% of type I spiral ganglion neurons. Four main age groups [postnatal days (P)5, P24, P90, and P180] were used. Additional animals received no surgery, partial removals, or complete removals at older ages. Three months after the cochlear removal the animals were reanesthetized and perfused. The brainstem and the temporal bones were wax-embedded, frontally sectioned, and Nissl-stained. Sections of the right and left cochlear nuclei were compared quantitatively. Removal of the cochlea at P5 resulted in the loss of more than 50% of large (nongranular) neurons throughout the ipsilateral cochlear nucleus. Lesions at older ages did not produce any neuron loss. The size of the remaining neurons was reduced by 10-15% in all age groups. Partial lesions at P5 produced a graded response in the cochlear nucleus that was related to the extent of the lesion. The developmental sensitive period for the effects of cochlear removal on the ferret cochlear nucleus is therefore over before the age (P28-P30) at which the animal begins to hear. The present result differs markedly from the chicken, in which the sensitive period for removal of the cochlea persists for at least 2 months after the onset of hearing.

Afferent Pathways↗

Chronic microstimulation in the feline ventral cochlear nucleus: physiologic and histologic effects.

This study was conducted to help to establish the feasibility of a multi-channel auditory prosthesis based on microstimulation within the human ventral cochlear nucleus, and to define the range of stimulus parameters that can be used safely with such a device. We chronically implanted activated iridium microelectrodes into the feline ventral cochlear nucleus and, beginning 80-250 days after implantation, they were pulsed for 7 h/day, on up to 21 successive days. The stimulus was charge-balanced pulses whose amplitude was modulated by a simulated human voice. The pulse rate (250 Hz/electrode) and the maximum pulse amplitude were selected as those that are likely to provide a patient with useful auditory percepts. The changes in neuronal responses during the multi-day stimulation regimens were partitioned into long-lasting, stimulation-induced depression of neuronal excitability (SIDNE), and short-acting neuronal refractivity (SANR). Both SIDNE and SANR were quantified from the changes in the growth functions of the evoked potentials recorded in the inferior colliculus. All of the stimulation regimens that we tested induced measurable SIDNE and SANR. The combined effect of SIDNE and the superimposed SANR is to depress the neuronal response near threshold, and thereby, to depress the population response over the entire amplitude range of the stimulus pulses. SIDNE and SANR may cause the greatest degradation of the performance of a clinical device at the low end of the amplitude range, and this may represent an inherent limitation of this type of spatially localized, high-rate neuronal stimulation. We determined sets of stimulus parameters which preserved most of the dynamic range of the neuronal response, when using either long (150 micros/phase) or short (40 micros/phase) stimulus pulses. Increasing the amplitude of the stimulus was relatively ineffective as a means of increasing the dynamic range of neuronal response, since the greater stimulus amplitude induced more SIDNE. All of the pulsed and unpulsed electrode sites were examined histologically, and no neuronal changes attributable to the stimulation were detected. There was some aggregation of glial cells immediately adjacent to some of the electrodes that were pulsed with the short-duration pulses, and at the highest current densities.

Animals↗

Distribution of glycine and GABA immunoreactivities in the cochlear nucleus: quantitative patterns of putative inhibitory inputs on three cell types.

Postembedding immunocytochemistry was used to compare the distribution of GABA and glycine immunoreactive labelling in the cochlear nucleus, in particular the number of immunolabeled synaptic boutons apposing the cell body profiles of three major neuronal types. The proportions and absolute numbers of glycine immunoreactive puncta were greatest on fusiform cell body profiles. Glycine immunoreactive puncta also predominated on spherical cell body profiles, although GABA immunoreactive boutons were more abundant than on fusiform cells. Octopus cell body profiles were apposed by the fewest immunoreactive puncta. Puncta colabeled for glycine and GABA were frequently observed on all three cell types. These findings suggest that each major cell type possesses a distinct pattern of glycinergic and GABAergic input, with glycinergic input predominating. Since both tuberculoventral and cartwheel neurons were immunolabeled and are known to project intrinsically, it is clear that a large percentage of glycinergic and GABAergic input to cochlear nucleus neurons originates from intrinsic sources.

Animals↗

Development of oriented dendritic fields in the dorsal cochlear nucleus of the hamster.

The shapes of the apical and basal dendritic fields of the fusiform cells in the dorsal cochlear nucleus of the hamster were analyzed quantitatively. Measurements of the cross-sectional areas of the dendritic fields in planes parallel and perpendicular to planes occupied by the cochlear nerve axons revealed that the apical dendrites have a preferential orientation with respect to the cochlear planes. No consistent orientation of the basal dendrites was apparent. The orientation of the apical dendrites is not present in the neonatal hamster; rather, it develops gradually and is not fully established until after postnatal day 25. Since the cochlear fibers grow into the dorsal cochlear nucleus, establish contacts and become functional before day 25, the presence of the cochlear input might be a prerequisite for the development of oriented dendritic trees. In adult hamsters that have had their cochlear input eliminated during infancy, the apical dendritic trees of the fusiform cells are not oriented normally. The results suggest that the presence of the afferent input is necessary for the differential growth that leads to the development of oriented dendritic trees.

Animals↗

Representation of vowel stimuli in the ventral cochlear nucleus of the chinchilla.

Responses of neurons in the ventral cochlear nucleus (VCN) of anesthetized chinchillas to six synthetic vowel sounds (/a/, /e/, /epsilon/, /i/, /o/ and /u/) were recorded at several intensity levels. Stimuli were synthesized with a fundamental frequency of 100 Hz or 181.6 Hz and had formant values at integer multiples of 100 Hz. Responses came from most neuron types in the VCN (with the exception of onset cells with an I-shaped pattern). Population studies, performed only on primary-like (PL) and chopper neurons, showed that PL neurons provide a better temporal representation than do chopper neurons. At the lowest level of stimulation, all neuron types provide an accurate rate-place representation of vowel spectra. With an increase in stimulus level, the rate-place representation of PL neurons becomes inferior to that of chopper neurons, either sustained choppers or transient choppers.

Acoustic Stimulation↗

Vessicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus.

Projections of glutamatergic somatosensory and auditory fibers to the cochlear nucleus (CN) are mostly nonoverlapping: projections from the spinal trigeminal nucleus (Sp5) terminate primarily in the granule cell domains (GCD) of CN, whereas type I auditory nerve fibers (ANFs) project to the magnocellular areas of the VCN (VCNm) and deep layers of Dorsal CN (DCN). Vesicular glutamate transporters (VGLUTs), which selectively package glutamate into synaptic vesicles, have different isoforms associated with distinct subtypes of excitatory glutamatergic neurons. Here we examined the distributions of VGLUT1 and VGLU2 expression in the CN and their colocalization with Sp5 and ANF terminals following injections of anterograde tracers into Sp5 and the cochlea in the guinea pig. The CN regions that showed the most intense expression of VGLUT1 and VGLUT2 were largely nonoverlapping and were consistent with ANF and Sp5 projections, respectively: VGLUT1 was highly expressed in VCNm and the molecular layer of the DCN, whereas VGLUT2 was expressed predominantly in the GCD. Half (47% +/- 3%) of the Sp5 mossy fiber endings colabeled with VGLUT2, but few (2.5% +/- 1%) colabeled with VGLUT1. In contrast, ANFs colabeled predominantly with VGLUT1. The pathway-specific expression of VGLUT isoforms in the CN may be associated with the intrinsic synaptic properties that are unique to each sensory pathway.

Afferent Pathways↗

Fibroblast growth factors (FGFs) in the cochlear nucleus of the adult mouse following acoustic overstimulation.

To see if fibroblast growth factors (FGFs) might function in the central changes following auditory overstimulation we tracked immunostaining in the cochlear nucleus of adult mice with monoclonal antibodies to FGFs (FGF-1, FGF-2) and FGF receptor. After exposure nearly all outer hair cells died, while inner hair cell and fiber loss were restricted to a region midway along the cochlear spiral. FGFs staining in the cochlear nucleus appeared in hypertrophied astrocytes in the regions of nerve fiber degeneration only. For normal-sized astrocytes there was an increase in the number stained and the intensity of staining across all frequency domains, but not in neurons. The increases were modest at 3-7 days, pronounced at 14 days, modest again by 30 days, and back to control levels by 60 days. FGF receptor staining of neurons occurred equally in all mice, exposed or not. The findings suggest that astrocytes play a role in the central responses to acoustic overstimulation and cochlear damage, involving FGFs, possibly regulating the activity of intrinsic neurons or signaling axonal growth. Not limited to regions of cochlear nerve fiber and inner hair cell loss, the changes in FGFs may represent a reaction to outer hair cell damage which spreads broadly across the central pathways.

Animals↗

Effects of intense tone exposure on choline acetyltransferase activity in the hamster cochlear nucleus.

Choline acetyltransferase (ChAT) activity has been mapped in the cochlear nucleus (CN) of control hamsters and hamsters that had been exposed to an intense tone. ChAT activity in most CN regions of hamsters was only a third or less of the activity in rat CN, but in granular regions ChAT activity was similar in both species. Eight days after intense tone exposure, average ChAT activity increased on the tone-exposed side as compared to the opposite side, by 74% in the anteroventral CN (AVCN), by 55% in the granular region dorsolateral to it, and by 74% in the deep layer of the dorsal CN (DCN). In addition, average ChAT activity in the exposed-side AVCN and fusiform soma layer of DCN was higher than in controls, by 152% and 67%, respectively. Two months after exposure, average ChAT activity was still 53% higher in the exposed-side deep layer of DCN as compared to the opposite side. Increased ChAT activity after intense tone exposure may indicate that this exposure leads to plasticity of descending cholinergic innervation to the CN, which might affect spontaneous activity in the DCN that has been associated with tinnitus.

Analysis of Variance↗