Animal model studies yield translational solutions for cochlear drug delivery.

The field of hearing and deafness research is about to enter an era where new cochlear drug delivery methodologies will become more innovative and plentiful. The present report provides a representative review of previous studies where efficacious results have been obtained with animal models, primarily rodents, for protection against acute hearing loss such as acoustic trauma due to noise overexposure, antibiotic use and cancer chemotherapies. These approaches were initiated using systemic injections or oral administrations of otoprotectants. Now, exciting new options for local drug delivery, which opens up the possibilities for utilization of novel otoprotective drugs or compounds that might not be suitable for systemic use, or might interfere with the efficacious actions of chemotherapeutic agents or antibiotics, are being developed. These include interesting use of nanoparticles (with or without magnetic field supplementation), hydrogels, cochlear micropumps, and new transtympanic injectable compounds, sometimes in combination with cochlear implants.

A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus.

Large conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins. LS3 suppresses locomotor activity via a BK channel-specific mechanism in wild-type or BK channel-humanized Caenorhabditis elegans. Topical application on the dural surface of the auditory midbrain in mouse suppresses sound evoked neural activity, similar to a well-characterized pore blocker of the BK channel. Moreover, this novel ion channel-targeted peptide rapidly crosses the BBB after systemic delivery to modulate auditory processing. Thus, a potent BK channel peptide modulator is open to neurological applications, such as preventing audiogenic seizures that originate in the auditory midbrain.

Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.

Age-related hearing loss - presbycusis - is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate GABAA receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit ß2, and N-methyl-d-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6 to 49kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. SGN density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1amplitude. mRNA and protein expression of GABAAR α1 and AChR ß2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss.

Reorganization of receptive fields following hearing loss in inferior colliculus neurons.

We explored frequency and intensity encoding in the inferior colliculus (IC) of the C57 mouse model of sensorineural hearing loss. Consistent with plasticity reported in the IC of other models of hearing loss, frequency response areas (FRAs) in hearing-impaired (HI) mice were broader with fewer high-frequency units than normal-hearing (NH) mice. The broad FRAs recorded from HI mice had lower cutoffs on the low frequency edge of the FRA. Characteristic frequency (CF) and sharpness of tuning (Q10) calculated from the FRA were used to divide the sample into four categories: low-CF sharp-FRA, low-CF broad-FRA, high-CF sharp-FRA, and high-CF broad-FRA units. Rate-intensity functions (RIFs) for CF tones and noise were used to determine the minimum and maximum response counts as well as the sound pressure levels resulting in 10%, 50%, and 90% of the maximum spike count. Tone RIFs of broad FRA units were shifted to the right of tone RIFs of sharp FRA units in both NH and HI mouse IC, regardless of the unit CF. The main effects of hearing loss were seen in the noise RIFs. The low-CF broad-FRA units in HI mice had elevated responses to noise, and the high-CF sharp-FRA units in HI mice had lower maximum rates, as compared with the units recorded from NH mice. These results suggest that, as the IC responds to peripheral hearing loss with changes in the representation of frequency, an altered balance between inhibitory and excitatory inputs to the neurons recorded from the HI mice alters aspects of the units' intensity encoding. This altered balance likely occurs, at least in part, outside of the IC.

Short communication: Effect of subacute ruminal acidosis on in situ fiber digestion in lactating dairy cows.

Subacute ruminal acidosis (SARA) was induced by replacing 25% of the total mixed ration intake [dry matter (DM) basis] with pellets consisting of 50% wheat and 50% barley. This reduced dietary forage content (DM basis) from 39.7 to 29.8% and increased the dietary concentrate content from 60.3 to 70.2%. Induction of SARA reduced the 24- and 48-h in situ neutral detergent fiber (NDF) degradabilities of grass hay numerically from 31.5% to 24.6% (P = 0.29) and from 51.3% to 36.9% (P < 0.05), respectively. The 24- and 48-h in situ NDF degradabilities of legume hay were reduced from 35.3 to 26.3% (P < 0.05) and from 49.0 to 35.8% (P < 0.05), respectively. The 24- and 48-h in situ NDF degradabilities of corn silage were reduced from 44.0 to 37.2% (P < 0.05) and from 56.1 to 44.8% (P < 0.05), respectively. This study suggests that induction of SARA by excess feeding of wheat/barley pellets reduces the rumen digestion of NDF from grass hay, legume hay, and corn silage.

Effects of a monensin controlled-release capsule or premix on attenuation of subacute ruminal acidosis in dairy cows.

The effects of monensin, administered either as a controlled release capsule (CRC) or a premix, on attenuating grain-induced subacute ruminal acidosis (SARA) and on ruminal fermentation characteristics in Holstein cows receiving a total mixed ration were investigated in two experiments. In both experiments, six multiparous, rumen-fistulated Holstein cows were used in a two-treatment, two-period crossover design with 6-wk periods. In Experiment 1, treatments were either a monensin CRC or a placebo CRC. In Experiment 2, treatments were either a monensin premix or a placebo premix. In both experiments, at the beginning of wk 4 SARA was induced in experimental cows for a 10-d period with a grain challenge model, and ruminal pH was measured continuously using indwelling pH probes. The administration of monensin either as a CRC or a premix had no effect on ruminal pH characteristics. Neither monensin CRC nor premix had an effect on ruminal volatile fatty acid concentrations, but reduced the acetate:propionate ratio. Monensin premix-treated cows were observed to have increased milk yield, largely as a result of a higher dry matter intake in monensin-treated cows compared to control cows. Milk fat content and yield were lower in monensin-treated cows compared to placebo-treated cows during SARA. In conclusion, there is no evidence that monensin was efficacious in raising ruminal pH during SARA under the conditions employed in this study.

The effects of dietary flax oil and antioxidants on ascites and pulmonary hypertension in broilers using a low temperature model.

1. Three experiments were conducted using a low temperature model to induce pulmonary hypertension (PH) and ascites in broiler chickens. Diets containing 25 g or 50 g flax oil/kg food and control diets with an equivalent amount of animal/vegetable (A/V) blend oil, with and without supplemental antioxidants (vitamin C and vitamin E) were used. The amount of PH was assessed by the ratio of right ventricle weight to total ventricle weight (RV/TV ratio). Birds were considered to suffer from pulmonary hypertension syndrome (PHS) if the RV/TV ratio was greater than 0.299. 2. In experiment 1, the test diets contained 50 g oil/kg food and were given during the grower period only. Birds fed on the flax oil diet tended to have a lower incidence of PHS, ascites and lower RV/TV ratios than birds fed on the control diet. However, when the flax oil diet was supplemented with antioxidants, the incidence of ascites, PHS, haematocrit and whole blood and plasma viscosity increased compared with birds fed on the flax oil diet without antioxidants. These effects were not seen in experiment 2, when the test diets containing 30 g oil/kg food (25 g flax oil plus 5 g A/V blend oil/kg food compared to 30 g A/V blend oil/kg food) were given during the grower period. However, in experiment 3, when the test diets containing 30 g oil/kg food were given from day 1 to week 8, birds fed on the control diet supplemented with antioxidants had a higher incidence of PHS than those fed on the control diet alone. 3. In all 3 experiments, there was no significant effect of dietary fat source or supplemental antioxidants on total food intake or food conversion. 4. We conclude that diets containing 50 g flax oil/kg food tend to reduce the incidence of PHS and ascites in broilers using a low temperature model but the results were not statistically significant. In some cases, supplementing diets with a combination of vitamin E and vitamin C increased the incidence of ascites and PHS.

Background noise differentially effects temporal coding by tonic units in the mouse inferior colliculus.

In natural environments, temporally complex signals often occur in a background of noise. The neural mechanisms underlying the preservation of temporal sensitivity in background noise are poorly understood. In the present study, we examined the ability of inferior colliculus (IC) units with primary-like and sustained response patterns ('tonic units') to encode silent gaps in quiet and in background noise. Minimum gap thresholds (MGTs), the shortest silent gap in a noise burst evoking a neural response, were measured in quiet and background noise for 34 IC units. Units were classified as background noise resistant (BNR; MGT did not change in background noise) or background noise sensitive (BNS; MGTs became elevated in background noise). In quiet, the MGTs of BNR and BNS units were comparable and both types of units encoded the gap by a cessation of activity during the gap. The addition of background noise had little effect on the response rate of BNR units either during or after the gap stimulus. In contrast, for BNS units, background noise reduced the response rate during the gap stimulus while increasing the response rate after the gap stimulus. Background noise also altered the first spike latency of BNS units. For BNS units, the mean first spike latency was no longer inversely related to BF, but this relationship was maintained in BNR units. These results suggest that the response of BNS units to background noise obliterates their response to the gap stimulus.

Short communication: effects of monensin on 3-methylhistidine excretion in transition dairy cows.

Urinary 3 methyl-histidine excretion was measured in high yielding dairy cows between 10 and 3 d precalving and between 3 and 9 d postcalving. Cows received a sodium monensin controlled-release capsule or a placebo 3 wk before calving. Monensin did not affect urinary 3 methyl-histidine. Average urinary 3 methyl-histidine excretion was significantly higher postcalving (4.11 mmol d(-1)) than precalving (2.48 mmol d(-1)). This increase is assumed to be predominantly due to the negative nitrogen balance in the postcalving period caused by insufficient nutrient intake to meet nutrient requirements, which necessitates catabolism of mainly myofibrillar protein.

Effect of dietary flax oil and hypobaric hypoxia on pulmonary hypertension and haematological variables in broiler chickens.

1. Three experiments were conducted with broiler chickens using hypobaric chambers and control pens, feeding diets containing 25 or 50 g flax oil/kg food or control diets with equivalent amounts of animal/vegetable (A/V) blend oil for 4 weeks. The effect of these diets on haematological variables and the extent of right ventricular hypertrophy (RVH) leading to ascites was determined. 2. Overall growth rate was not consistently affected by dietary treatment, although feeding the 25 g flax oil/kg diet reduced weight gain in week 4 of one experiment. Feeding the 50 g flax oil/kg diet but not the 25 g flax oil/kg diet reduced RVH in birds exposed to hypobaric conditions compared to feeding control diets. 3. Feeding the 50 g flax oil/kg diet under hypobaric conditions reduced the haematocrit and haemoglobin content, increased the erythrocyte deformability and the proportion of unsaturated fatty acids in the erythrocyte membranes, and reduced the whole blood viscosity compared to feeding control diets. These effects were not seen when the 25 g flax oil/kg diet was fed. The ratio of n-3 to n-6 fatty acids in erythrocyte membranes was increased in the 50 g flax oil/kg treatment group compared to controls. 4. Including 50 g flax oil/kg broiler diet reduces RVH in broiler chickens. This may be attributable in part to an increase in erythrocyte deformability from an increased proportion of unsaturated fatty acids in the erythrocyte membranes.

Age-related alteration in processing of temporal sound features in the auditory midbrain of the CBA mouse.

The perception of complex sounds, such as speech and animal vocalizations, requires the central auditory system to analyze rapid, ongoing fluctuations in sound frequency and intensity. A decline in temporal acuity has been identified as one component of age-related hearing loss. The detection of short, silent gaps is thought to reflect an important fundamental dimension of temporal resolution. In this study we compared the neural response elicited by silent gaps imbedded in noise of single neurons in the inferior colliculus (IC) of young and old CBA mice. IC neurons were classified by their temporal discharge patterns. Phasic units, which accounted for the majority of response types encountered, tended to have the shortest minimal gap thresholds (MGTs), regardless of age. We report three age-related changes in neural processing of silent gaps. First, although the shortest MGTs (1-2 msec) were observed in phasic units from both young and old animals, the number of neurons exhibiting the shortest MGTs was much lower in old mice, regardless of the presentation level. Second, in the majority of phasic units, recovery of response to the stimulus after the silent gap was of a lower magnitude and much slower in units from old mice. Finally, the neuronal map representing response latency versus best frequency was found to be altered in the old IC. These results demonstrate a central auditory system correlate for age-related decline in temporal processing at the level of the auditory midbrain.

Gap encoding by inferior collicular neurons is altered by minimal changes in signal envelope.

Neural correlates of temporal resolution in the central auditory system are currently under intense investigation. The gap detection paradigm offers a simple, yet important, test of temporal acuity because changes in behavioral gap thresholds have been correlated with deficits in complex stimulus processing, such as speech perception. In gap detection studies, silent gaps are typically shaped by rapid (< 1.0 ms) rise/fall (R/F) times, i.e., rapid decreases and increases in sound intensity. However, in nature, the envelopes surrounding silent periods can vary significantly in R/F time. Therefore, we investigated whether changes in the R/F time surrounding the silent gap affect neural processing by inferior collicular (IC) neurons. Gap R/F times were varied between 0.5 and 16 ms and the discharge pattern, response rate, and first spike latency of IC neurons were measured for gap widths up to 100 ms. Neurons were classified into phasic or tonic discharge patterns based on peri-stimulus time histograms elicited to 100 ms noise carriers. The results indicate that (1) minimal gap thresholds increased with R/F time regardless of response type, (2) first spike latency variance increased systematically with R/F time for units which had small first spike standard deviations at short R/F times, and (3) the response rate of some units (called 'gap-tuned') changed as a function of both R/F time and gap width. Gap-tuned units responded strongly to a particular gap width only when the envelope of the gap was shaped by a particular R/F time. For gap-tuned units, increases in R/F time shifted the tuning to larger gap widths and also broadened the response profile. These results show that temporal acuity of neurons in the IC, as measured by the gap detection paradigm, is sensitive to the envelope surrounding gaps embedded in noise carriers.

Inputs to a physiologically characterized region of the inferior colliculus of the young adult CBA mouse.

Presbycusis is a sensory perceptual disorder involving loss of high-pitch hearing and reduced ability to process biologically relevant acoustic signals in noisy environments. The present investigation is part of an ongoing series of studies aimed at discerning the neural bases of presbycusis. The purpose of the present experiment was to delineate the inputs to a functionally characterized region of the dorsomedial inferior colliculus (IC, auditory midbrain) in young, adult CBA mice. Focal, iontophoretic injections of horseradish peroxidase were made in the 18-24 kHz region of dorsomedial IC of the CBA strain following physiological mapping experiments. Serial sections were reacted with diaminobenzidine or tetramethylbenzidine, counterstained and examined for retrogradely labeled cell bodies. Input projections were observed contralaterally from: all three divisions of cochlear nucleus; intermediate and dorsal nuclei of the lateral lemniscus (LL); and the central nucleus, external nucleus and dorsal cortex of the IC. Input projections were observed ipsilaterally from: the medial and lateral superior olivary nuclei; the superior paraolivary nucleus; the dorsolateral and anterolateral periolivary nuclei; the dorsal and ventral divisions of the ventral nucleus of LL; the dorsal and intermediate nuclei of LL; the central nucleus, external nucleus and dorsal cortex of the IC outside the injection site; and small projections from central gray and the medial geniculate body. These findings in young, adult mice with normal hearing can now serve as a baseline for similar experiments being conducted in mice of older ages and with varying degrees of hearing loss to discover neural changes that may cause age-related hearing disorders.

Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse.

The gap detection paradigm is frequently used in psychoacoustics to characterize the temporal acuity of the auditory system. Neural responses to silent gaps embedded in white-noise carriers, were obtained from mouse inferior colliculus (IC) neurons and the results compared to behavioral estimates of gap detection. Neural correlates of gap detection were obtained from 78 single neurons located in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed from single-unit gap functions and were found to be comparable, 1-2 ms, to the behavioral gap threshold (2 ms). There was no difference in MGTs for units in which both carrier intensities were collected. Single unit responses were classified based on temporal discharge patterns to steady-state noise bursts. Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by sustained units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were obtained for inhibitory neurons (x = 14 ms). Finally, the time-course of behavioral and neurophysiological gap functions were found to be in good agreement. The results of the present study indicate the neural code necessary for behavioral gap detection is present in the temporal discharge patterns of the majority of IC neurons.

Efferent projections of a physiologically characterized region of the inferior colliculus of the young adult CBA mouse.

The present investigation is part of an ongoing series of studies aimed at discerning the neural bases of presbycusis. Presbycusis is a sensory perceptual disorder involving loss of high-pitch hearing and reduced ability to process biologically relevant acoustic signals in noisy environments. The purpose of the present experiment was to delineate the efferent projections of a functionally characterized region of the dorsomedial inferior colliculus (IC, auditory midbrain) in young, adult CBA mice. The CBA strain's progressive loss of hearing over its lifespan approximates many aspects of the mild-to-moderate hearing loss experienced by a significant number of humans suffering from presbycusis. Focal, iontophoretic injections of HRP were made in the 18-24 kHz region of dorsomedial IC of the CBA strain following physiological mapping experiments. Serial sections were reacted with a chromagen, counterstained and examined for anterogradely labeled fibers and boutons. Efferent projections were observed ipsilaterally in: medial and ventral divisions of the medial geniculate body (MGB); middle layers of the superior colliculus; central gray; and external nucleus (E), dorsal cortex (DC) and central nucleus of IC. Contralaterally, labeled fibers and boutons were seen in the IC at a location homologous to the injection site, as well as in E and DC. A small projection was noted in contralateral MGB. These findings in young, adult mice with normal hearing can now serve as a baseline for similar experiments being conducted in mice and animals of other species of older ages and with varying degrees of hearing loss.

Nimodipine at a dose that slows ABR latencies does not protect the ear against noise.

We tested the hypothesis that nimodipine, a dihydropyridine reported to increase blood flow, block calcium and potassium channels, and reduce ischemic damage, would alleviate noise-induced hearing loss. Young C57B1/6J mice were exposed to wide-band noise (2 min, 120 dB SPL), with ABR thresholds (4-50 kHz) determined before noise exposure, and from 1 h to 2 weeks afterwards. One group (n = 7) received nimodipine (30 mg/kg/day) in daily peanut butter food supplements beginning 24 h before exposure; the other group (n = 6) received peanut butter alone. In the pretest nimodipine significantly increased the latency of Wave P1 of the ABR (mean difference: 0.16 ms; P < 0.02), showing that calcium blockade depressed sensorineural efficiency, but ABR thresholds were not affected. Noise exposure produced a severe threshold loss that partially recovered in the first week after exposure, and then suffered a slight but significant loss in the second week. These effects were seen equally in both groups: nimodipine did not reduce the severity of the immediate hearing loss following noise exposure, nor did it benefit recovery.

Preservation of amplitude modulation coding in the presence of background noise by chinchilla auditory-nerve fibers.

Sound envelope temporal fluctuations are important for effective processing of biologically relevant acoustic information including speech, animal vocalizations, sound-source location, and pitch. Amplitude modulation (AM) of sound envelopes can be encoded in quiet with high fidelity by many auditory neurons including those of the auditory nerve (AN) and cochlear nucleus. From both neurophysiological and clinical perspectives, it is critical to understand the effects of background masking noise on the processing of AM. To further this goal, single-unit recordings were made from AN fibers in anesthetized chinchillas. Units were classified according to spontaneous firing rate (SR) and threshold. Best frequency (BF) pure-tone bursts and AM (10-500 Hz) tone bursts were employed as stimuli at several sound levels, both in quiet and in the presence of a continuous wideband noise. It was found that (1) in quiet, low SR AN fibers show the strongest AM coding, followed in order by medium SR and high SR fibers, respectively. (2) AN units of all three classes generally preserve their AM coding even in the presence of loud (0 or +6 dB S/N) background noise and at high sound levels (over 75 dB SPL). (3) This preservation is usually achieved by lowering the average firing rate proportionately to decreases in the synchronous (fundamental frequency) response. (4) For a few AN fibers, the AM coding increases or is reduced in the presence of the background noise. These findings suggest that AN preservation of AM coding in the presence of a continuous masking noise results from shifts in the operating ranges and firing rates of AN fibers resulting from cochlear nonlinearities and adaptive mechanisms.

Synaptic loss in the central nucleus of the inferior colliculus correlates with sensorineural hearing loss in the C57BL/6 mouse model of presbycusis.

Between 3 and 25 months of age, light and electron microscopic features of principal neurons in the central nucleus of the inferior colliculus of the C57BL/6 mouse were quantitated. This mouse strain has a genetic defect producing progressive sensorineural hearing loss which starts during young adulthood (2 months of age) with high-frequency sounds. During the second year of life, hearing is severely impaired, progressively involving all frequencies. The hearing loss was documented in the present study by auditory brainstem recordings of the mice at various ages. The cochleas from many of the same animals showed massive loss of both inner and outer hair cells beginning at the base (high-frequency region) and progressing with age along the entire length to the apex (low-frequency region). In the inferior colliculi, there was a significant decrease in the size of principal neurons in the central nucleus. There was a dramatic decrease in the number of synapses of all morphologic types on principal neuronal somas. The percentage of somatic membrane covered by synapses decreased by 67%. A ventral (high frequency) to dorsal (low frequency) gradient of synaptic loss could not be identified within the central nucleus. These synaptic changes may be related to the equally dramatic physiologic changes which have been noted in the central nucleus of the inferior colliculus, in which response properties of neurons normally sensitive to high-frequency sounds become more sensitive to low-frequency sounds. The synaptic loss noted in this study may be due to more than the loss of primary afferent pathways. It may represent alterations of the complex synaptic circuitry related to the central deficits of presbycusis.

Sensorineural hearing loss alters recovery from short-term adaptation in the C57BL/6 mouse.

Several strains of laboratory mouse (Mus musculus) have a pattern of hearing loss which resembles that found in humans. The C57BL/6 strain of mouse has a genetic defect that results in degeneration of the organ of Corti, originating in the basal, high-frequency region and then proceeding apically over time. The end result is a severe-to-profound sensorineural hearing loss (SNHL) by 14 months of age. In contrast, auditory function of the CBA strain remains normal through its early life span then slowly declines later in life, much like that typified by human presbycusis. The purpose of the present study was to compare ABR (peak 5) forward masking recovery functions in young, normal-hearing CBA and C57BL/6 mice to hearing-impaired C57BL/6 mice. ABR audiograms were obtained prior to collecting the tone-on-tone forward masking data. Masking was defined as a 50% reduction in the P5 component of the ABR, elicited and masked by 12 kHz tone bursts, using masker/probe time delays from 0 to 100 ms. Time constants were computed from an exponential model fit to the recovery functions (masker level vs. time delay). In hearing-impaired animals there was a significant increase in recovery from short-term adaptation as measured by the time constants, as well as a significant latency shift in the P5 component. The effects of SNHL on the recovery of the P5 component from short-term adaptation was comparable to that reported behaviorally for human hearing-impaired listeners and physiologically from the inferior colliculus (IC) of chinchillas suffering permanent threshold shifts.

Distribution of calbindin D-28k immunoreactivity in the cochlear nucleus of the young adult chinchilla.

Calbindin is a 28 kD calcium-binding protein found in neural tissue. Although its functional role in nerve cell physiological processing is still uncertain, previous investigations have suggested that because of its intracellular calcium buffering and regulation properties, it could influence temporal precision of neuronal firing to subserve temporal processing in the auditory brainstem, or could mediate monaural versus binaural coding, or be involved in synaptic plasticity (learning). The present study demonstrates differential calbindin immunoreactivity in the cochlear nuclear complex of the chinchilla, a rodent with exceptionally good low-frequency hearing. The most intense labeling in the cochlear cochlear nucleus was in somata of cartwheel and fusiform cells of the fusiform cell layer, and somata and process of the molecular layer of the dorsal cochlear nucleus (DCN). Only a relatively few scattered neurons were stained in the deep layers of DCN. In contrast, moderate labeling of neurons and neuropil throughout the ventral cochlear nucleus was seen. For instance, moderately stained spherical and elongate cells of the anteroventral cochlear nucleus were observed in contact with labeled puncta and amidst stained fibers. In the cochlear nerve root region, stained auditory nerve fibers and global cells were noted. In the posteroventral cochlear nucleus, principal cells of elongate and octopus shape were observed, in contact with labeled swellings and surrounded by labeled neuropil.