Biomedical subjects

D M Caspary

Publications and source records attributed to D M Caspary.

At least 19 recordsLinked to original sources

PubMed2000

Down-regulation of inhibition following unilateral deafening.

Physiological and neurochemical experiments described here suggest that unilateral deafening causes a reduction in inhibition in the adult gerbil inferior colliculus (IC) contralateral to the deafened ear. Multiple-unit recordings were made from single electrode penetrations in the IC prior to and directly after contralateral cochlear ablation. These recordings showed up to 60% increases in the proportion of sampled loci at which neural activity excited by ipsilateral stimulation was observed after the ablation. Novel excitatory responses were evident within minutes of the ablation. Western blotting for glutamic acid decarboxylase protein levels showed significant decreases in the IC contralateral to cochlear ablation, relative to those in the ipsilateral IC, at 24 h and 7 days survival after the ablation. Four hour or 1 year survival post-ablation did not produce significant contralateral/ipsilateral differences in relation to the control group. Taken together, these results suggest the presence of at least two, short-term mechanisms involved in the central response to cochlear removal, both of which appear to implicate a decreased inhibitory influence. One is a very rapid, stimulus-related, functional unmasking. The other is a more delayed reduction in the capacity of gamma-aminobutyric acid synthesis in the IC.

Animals↗

PubMed2000

Effects of chronic salicylate on GABAergic activity in rat inferior colliculus.

It is well accepted that salicylate ototoxicity results in reversible tinnitus in humans. Salicylate-induced tinnitus may be an example of plasticity of the central auditory system and could potentially serve as a model to further understand mechanisms of tinnitus generation. This study examined levels of glutamic acid decarboxylase (GAD) and the binding characteristics of the GABA(A) receptor in auditory brainstem structures of Long-Evans rats chronically treated with salicylate. Western blotting revealed a significant 63% (P<0.008) elevation of GAD levels in the inferior colliculus (IC) of salicylate-treated subjects. This occurred in subjects demonstrating behavioral evidence of tinnitus. Muscimol saturation analysis was indicative of a salicylate-related increase in receptor affinity. Linear regression of [(3)H]muscimol saturation analysis data revealed a significant (P<0.05) reduction in K(d) values in whole IC (-48%), as well as in the central nucleus of IC (CIC, -58%) and combined external and dorsal cortex of IC (E/DCIC, -46%). The number of GABA(A) binding sites (B(max)) were also significantly (P<0.05) decreased. These changes were observed only in central auditory structures. This suggests that GAD expression and GABA(A) receptor binding characteristics may be altered with chronic exposure to sodium salicylate and these changes may represent aberrant plasticity clinically experienced as tinnitus.

Animals↗

PubMed2000

GAD levels and muscimol binding in rat inferior colliculus following acoustic trauma.

Pharmacological studies of the inferior colliculus (IC) suggest that the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) plays an important role in shaping responses to simple and complex acoustic stimuli. Several models of auditory dysfunction, including age-related hearing loss, tinnitus, and peripheral deafferentation, suggest an alteration of normal GABA neurotransmission in central auditory pathways. The present study attempts to further characterize noise-induced changes in GABA markers in the IC. Four groups (unexposed control, 0 h post-exposure, 42 h post-exposure, and 30 days post-exposure) of 3-month-old male Fischer 344 rats were exposed to a high intensity sound (12 kHz, 106 dB) for 10 h. Observed hair cell damage was primarily confined to the basal half of the cochlea. There was a significant decrease in glutamic acid decarboxylase (GAD(65)) immunoreactivity in the IC membrane fraction compared to controls (P<0.05) at 0 h (-41%) and 42 h (-28%) post-exposure, with complete recovery by 30 days post-exposure (P>0.98). Observed decreases in cytosolic levels of GAD(65) were not significant. Quantitative muscimol receptor binding revealed a significant increase (+20%) in IC 30 days after sound exposure (P<0.05). These data suggest that changes in GABA neurotransmission occur in the IC of animals exposed to intense sound. Additional studies are needed to determine whether these changes are a result of protective/compensatory mechanisms or merely peripheral differentiation, as well as whether these changes preserve or diminish central auditory system function.

Animals↗

PubMed1999

Age-related changes in GABA(A) receptor subunit composition and function in rat auditory system.

A decline in the ability to discriminate speech from noise due to age-related hearing loss (presbycusis) may reflect impaired auditory information processing within the central nervous system. Presbycusis may result, in part, from functional loss of the inhibitory neurotransmitter GABA. The present study assessed age-related changes of the GABA(A) receptor in the inferior colliculus of young-adult, middle-aged, and aged rats related to: (i) receptor subunit composition and (ii) receptor function. Western blotting was used to measure protein levels of selected GABA(A) receptor subunits in preparations obtained from the inferior colliculus of Fischer 344 and Fischer 344/Brown-Norway F1 hybrid rats. In both strains, the aged group exhibited significant increases in gamma1 subunit protein and a decrease in alpha1 subunit protein. To examine the functional consequence of this putative age-related subunit change, we measured the ability of exogenous GABA to flux/translocate chloride ions into microsac preparations derived from Fischer 344 inferior colliculus. GABA-mediated chloride influx was significantly increased in samples prepared from the inferior colliculus of aged animals. Together with previous studies, these results strongly suggest an age-related change in GABA(A) receptor composition. These changes may reflect a compensatory up-regulation of inhibitory function in the face of significant loss of presynaptic GABA release. These findings provide one example of plastic neurotransmitter receptor changes which can occur during the ageing process.

Aging↗

PubMed1999

Detection of glutamate decarboxylase isoforms in rat inferior colliculus following acoustic exposure.

The inferior colliculus is a central auditory structure which serves as a site for the integration of ascending and descending auditory information. Changes in central auditory structures may occur with acoustic exposure, which cannot be explained by alterations in cochlear function alone. Rats were exposed to a 10-kHz tone at 100 dB SPL for 9 h. Auditory brainstem response measures showed an initial 25-30-dB threshold shift across all tested frequencies. By 30 days post-exposure, thresholds for clicks and most frequencies returned to near control levels; however, thresholds remained elevated at 10 and 20 kHz. Inner hair cell loss was confined to apical and basal ends of the cochlea, and did not exceed 20%. Inferior colliculus levels of the two isoforms of the GABA synthetic enzyme glutamate decarboxylase (65,000 and 67,000 mol. wt forms) were measured immediately post-exposure (0 h) and at two and 30 days post-exposure using quantitative immunocytochemical and western blotting techniques. Zero-hour measures revealed a significant increase in the level of glutamate decarboxylase (mol. wt 67,000) protein (118%), as well as in the optical density (35%) of immunolabeled cells. By 30 days post-exposure, inferior colliculus protein levels of both glutamate decarboxylase isoforms were significantly below unexposed controls (39% and 21% for the 65,000 and 67,000 mol. wt forms, respectively). These studies describe increased markers for GABA immediately following acoustic exposure, followed by a decline to below control levels from two to 30 days post-exposure. It remains to be determined whether noise trauma-induced changes in glutamate decarboxylase levels in the inferior colliculus reflect protective up-regulation in response to intense stimulation, followed by the establishment of new neurotransmitter equilibrium levels.

Animals↗

PubMed1999

Age-related changes in [3H]strychnine binding in the vestibular nuclei of rats.

Glycine plays an important role as a neurotransmitter in the four vestibular nuclei (VN). The objective of this study was to determine if the levels of glycine-receptor binding in the VN change as a function of age. Quantitative receptor autoradiography was performed on brainstem sections from three age groups (3, 18 and 26 months) of Fischer 344 rats to assess binding in the VN. Glycine receptors were localized using [3H]strychnine binding. Strychnine binding declined monotonically with increasing age, such that the level of strychnine binding in each of the VN in the 28-month-old animals was approximately one-half that in the 3-month-olds. The age-related decrease in levels of strychnine binding suggest altered glycinergic function in the VN, which may in turn contribute to disturbances in equilibrium observed in the elderly.

Aging↗

PubMed1999

Gamma-aminobutyric acidergic and glycinergic inputs shape coding of amplitude modulation in the chinchilla cochlear nucleus.

Amplitude modulation is a prominent acoustic feature of biologically relevant sounds, such as speech and animal vocalizations. Enhanced temporal coding of amplitude modulation signals is found in certain dorsal and posteroventral cochlear nucleus neurons when they are compared to auditory nerve. Although mechanisms underlying this improved temporal selectivity are not known, involvement of inhibition has been suggested. gamma-Aminobutyric acid- and glycine-mediated inhibition have been shown to shape the dorsal cochlear nucleus and posteroventral cochlear nucleus response properties to other acoustic stimuli. In the present study, responses to amplitude modulation tones were obtained from chinchilla dorsal cochlear nucleus and posteroventral cochlear nucleus neurons. The amplitude modulation carrier was set to the neuron's characteristic frequency and the modulating frequency varied from 10 Hz. Rate and temporal modulation transfer functions were compared across neurons. Bandpass temporal modulation transfer functions were observed in 74% of the neurons studied. Most cochlear nucleus neurons (90%) displayed flat or lowpass rate modulation transfer functions to amplitude modulation signals presented at 2540 dB (re: characteristic frequency threshold). The role of inhibition in shaping responses to amplitude modulation stimuli was examined using iontophoretic application of glycine or gamma-aminobutyric acidA receptor agonists and antagonists. Blockade of gamma-aminobutyric acidA or glycine receptors increased stimulus-evoked discharge rates for a majority of neurons tested. Synchronization to the envelope was reduced, particularly at low and middle modulating frequencies, with temporal modulation transfer functions becoming flattened and less bandpass in appearance. Application of glycine, gamma-aminobutyric acid or muscimol increased the modulation gain over the low- and mid-modulation frequencies and reduced the discharge rate across envelope frequencies for most neurons tested. These findings support the hypothesis that glycinergic and gamma-aminobutyric acidergic inputs onto certain dorsal cochlear nucleus and posteroventral cochlear nucleus neurons play a role in shaping responses to amplitude modulation stimuli and may be responsible for the reported preservation of amplitude modulation temporal coding in dorsal cochlear nucleus and posteroventral cochlear nucleus neurons at high stimulus intensities or in background noise.

Acoustic Stimulation↗

PubMed1998

Age-related glycine receptor subunit changes in the cochlear nucleus of Fischer-344 rats.

Previous studies have shown that levels of binding for the strychnine-sensitive glycine receptor in the cochlear nucleus (CN) of Fischer (F344) rats decrease with age. Given the major role glycine plays in normal CN function, changes in glycine-receptor activity may contribute to central presbycusis. To further evaluate the impact of age on glycine receptors, in situ hybridization was used to assess, in three age groups of F344 rats, changes in levels of gene expression for four of its subunits. When compared with the 3-month-old rats, expression of mRNAs for alpha1 and beta subunits in the anteroventral CN decreased significantly in the 18- and 27-month-old age groups, while mRNA expression for the alpha2 subunit increased. If protein expressions are similar, these subunit changes may alter the function of glycine receptors, thereby affecting binding to its ligands.

Aging↗

PubMed1997

Glycine immunoreactivity and receptor binding in the cochlear nucleus of C57BL/6J and CBA/CaJ mice: effects of cochlear impairment and aging.

Glycinergic neurons in the cochlear nucleus (CN) of C57BL/6J (C57) and CBA/CaJ (CBA) mice were studied by using immunocytochemical and receptor-binding techniques. Adult C57 mice exhibit progressive cochlear pathology as they age, whereas aging CBA mice retain good hearing. In the CN of old C57 mice (18 months) with severe hearing loss, the number of glycine-immunoreactive neurons decreased significantly. The number (Bmax) of strychnine-sensitive glycine receptors (GlyR) decreased significantly in the dorsal CN of old C57 mice. Significant effects were not observed in the CN of middle-aged C57 mice (with less-severe hearing loss) or in very old CBA mice (which do not exhibit severe hearing loss). The data suggest that the combination of severe hearing loss and old age results in deficits in one or more inhibitory glycinergic circuits in the CN.

Aging↗

PubMed1997

Alterations of GABAA receptor subunit mRNA levels in the aging Fischer 344 rat inferior colliculus.

The inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the central auditory structure, the inferior colliculus (IC). Studies in rat and human suggest that age-related changes in markers for GABA neurotransmission occur in the IC. In particular, these changes include findings indicative of an age-related increase in the efficacy/potency of GABA to inhibit ligand binding at the GABAA receptor picrotoxin site in the Fischer (F344) rat IC. Such changes in GABAA receptor modulation suggest the potential for an alteration in GABAA receptor subunit composition in the old rat IC. To test this idea, the present study used in situ hybridization to quantify age-related changes in GABAA receptor subunit mRNA levels in the three major subdivisions of the IC in the F344 rat: dorsal cortex (DCIC), external cortex (ECIC), and the central nucleus (CIC). In support of earlier findings of an age-related change in GABAA receptor modulation, the present study found: (1) GABAA receptor subunit mRNA levels were significantly altered in the IC of old rats, and (2) age-related changes in subunit levels appeared to be regionally selective and subunit specific. A highly significant increase in the level of the gamma 1 subunit mRNA was observed with little change in the levels of the alpha 1, beta 2, and gamma 2 subunit mRNAs. A nonstatistically significant increase in alpha 2 subunit mRNA was also observed. This observed increase in alpha 2 subunit mRNA could be important since previous expression studies have shown that the alpha 2 and gamma 1 subunits coassemble and are incorporated into GABAA receptors which appear to be more sensitive to GABA. If the observed changes in subunit mRNA levels with age correlate well with enhanced GABAA receptor function in the IC of old rats, this, in turn, may represent a compensatory mechanism in response to presynaptic GABAergic changes.

Aging↗

PubMed1997

Glycinergic and GABAergic inputs affect short-term suppression in the cochlear nucleus.

Most cochlear nucleus (CN) neurons exhibit short-term response suppression to a second stimulus in a paired-pulse (click), forward-masking, paradigm. The magnitude of suppression, which appears to be greater than that observed in acoustic nerve, is dependent on the temporal separation and/or relative intensities of the two stimuli. Recent evidence suggests that inhibitory circuitry ending on CN neurons may mediate this response suppression. Using extracellular recordings from single CN neurons, suppression was evaluated using a forward-masking paradigm. Responses to paired acoustic clicks (i.e., a 'masker' followed by an identical 'probe' click) were measured while the time interval between the masker and probe was varied systematically. The role of inhibitory circuitry in forward-masking in the CN was assessed by pharmacologic manipulation of the GABA(A) and glycine(I) (strychnine-sensitive) receptors. Blockade of glycinergic or GABAergic receptors by iontophoretic application of the antagonists, strychnine and bicuculline methiodide, decreased the effects of forward-masking by shortening recovery times of the probe response in 2/3 of the neurons tested. Conversely, agonist application (glycine, and GABA or muscimol) increased the magnitude of suppression and delayed recovery of the probe response relative to control values. These findings suggest that known circuits releasing glycine and/or GABA mediate short-term response suppression in some CN neurons.

Acoustic Stimulation↗

PubMed1996

Decreased GABA effectiveness in the inferior colliculus neurons during ethanol withdrawal in rats susceptible to audiogenic seizures.

The inferior colliculus (IC) is the initiation site in the neuronal network for audiogenic seizure (AGS) in rats undergoing ethanol withdrawal (ETX). Considerable evidence supports a role of gamma-aminobutyric acid (GABA)-mediated inhibition in normal acoustic processing in the IC. Altered GABA-mediated inhibition in the IC is suggested to be important in the control of AGS initiation. The present study used microiontophoresis to examine the effectiveness of GABA on acoustically-evoked neuronal responses in the central nucleus of the IC (ICc). GABA effectiveness was compared in normal controls and a group of animals displaying high audiogenic seizure susceptibility (100% AGS) (HAGS), and a group exhibiting a low (mean, 33%) incidence of AGS (LAGS). Ethanol was administered for 4 days in three daily doses (9-15 g/kg/day) sufficient to maintain a moderate degree of intoxication. Tonic-clonic seizures were observed in HAGS animals, while LAGS rats exhibited less severe seizures, consisting primarily of wild running. Iontophoretic application of GABA consistently inhibited ICc neuronal firing in controls and in animals undergoing ETX. However, the mean dose (current) of GABA required to produce a 50% reduction of the ICc neuronal firing in the HAGS group was nearly twice that of the control animals. The mean dose of GABA for 50% inhibition in the LAGS group was about one-half that of the control group. Both of these differences were statistically significant. These data suggest that decreased GABA effectiveness in the IC neurons of HAGS susceptible animals is an important mechanism contributing to the propagation of severe AGS seen during ETX in these animals.

Acoustic Stimulation↗

PubMed1996

GABAA receptor binding in the aging rat inferior colliculus.

The inhibitory neurotransmitter GABA has been shown to be critically involved in shaping neuronal responses to simple and complex acoustic stimuli in the inferior colliculus. Studies in the rat and human inferior colliculus have suggested significant changes in functions related to GABA neurotransmission occur in the aged. These changes include significant decreases in GABA content, GABA release, GABA neurons, glutamate decarboxylase enzymatic activity, and GABAB receptor binding. Such changes within the inferior colliculus may affect the ability of elderly listeners to process complex acoustic signals, particularly in the presence of background noise. The present study was designed to examine the regional distribution and effects of aging on GABAA receptor binding sites in the Fischer 344 rat inferior colliculus using in vitro quantitative receptor autoradiography. [3H]GABA binding to GABAA receptors was significantly reduced in the inferior colliculus of young adult (3 months) and aged (18-26 months) rats when compared to 2-month animals. However, no significant changes were observed after 3 months of age. Single concentrations of tritiated GABAA receptor ligands (muscimol, t-butylbicycloorthobenzoate, and flunitrazepam) revealed no significant age-related changes in receptor binding in the inferior colliculus between 3 and 26 months of age. To characterize further the pharmacology of the GABAA receptor in the inferior colliculus, GABA modulation of the picrotoxin binding site was examined using [3H]t-butylbicycloorthobenzoate. When increasing concentrations of GABA were added to the incubation buffer, a significant decrease in binding was observed in the inferior colliculus of rats in each age group. In aged rats, the dose-response curve was shifted to the left, indicating an increase in the potency of GABA to inhibit [3H]t-butylbicycloorthobenzoate binding. Although no changes in GABAA receptor binding were detected in the inferior colliculus after 3 months of age, a significant alteration in interaction between the GABA and picrotoxin binding sites was observed in the inferior colliculus of aged rats when compared to 3-month-old young adults. This difference appears to reflect an increased sensitivity of the receptor to GABA modulation in aged rats and, thus, may serve as a compensatory mechanism to enhance GABAA receptor function in response to a presynaptic loss of inhibition.

Aged↗

PubMed1996

Responses of young and aged Fischer 344 rat inferior colliculus neurons to binaural tonal stimuli.

The inferior colliculus (IC) is one nucleus of the central auditory system which displays age-related changes. Inputs to the IC use primarily the amino acid neurotransmitters glutamate and gamma-aminobutryic acid (GABA). Neurochemical and anatomical studies of the Fischer 344 (F344) rat IC have shown decreases in GABA and GABA receptor levels (see Caspary et al., 1995 for review). GABA neurotransmission affects binaural response properties in the IC (Faingold et al., 1991a, b; Vater et al., 1992a; Park and Pollak, 1993, 1994). We hypothesized that aged F344 rats would show alterations in binaural IC neuronal response properties due to an imbalance in the relative levels of inhibition and excitation. Extracellular recordings from 189 single units localized to the IC of anesthetized aged (24 month) F344 rats were compared to those obtained from 221 IC units in young adult (3 month) animals. Quantitative analyses were performed to determine the distribution of ipsilateral and binaural rate/intensity functions (RIFs) in the central nucleus of the IC and external cortex of the IC units. The majority of IC units in both young and aged F344 rats were not responsive to monaural ipsilateral characteristic frequency tone bursts. Although there was some shift in the distribution of binaural RIF shapes with age, it was not statistically significant. The shift included a reduction in the percentage of units classified as E/I (excited by contralateral stimulation/ipsilaterally inhibited during binaural stimulation), but an increase with age in the percentage of units classified as E/f (excited by contralateral stimulation/ further facilitated by the addition of low intensity ipsilateral stimulation, but inhibited by higher intensity ipsilateral stimulation). Despite the role of inhibitory neurotransmission in binaural processing in the IC, age-related neurochemical deficits in the IC do not appear to result in a major deficit in the processing of simple binaural stimuli in F344 rats.

Acoustic Stimulation↗

PubMed1996

Physiology of the young adult Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli.

This study was designed to establish the young adult (3 month) Fischer 344 (F344) rat as a model of inferior colliculus (IC) physiology, providing a baseline for analysis of changes in single unit responses as the animals age and for the study of noise induced hearing loss. The response properties of units localized to the central nucleus of the IC (CIC) and those localized to the external cortex of the IC (ECIC) were compared in order to better characterize differences between these two subnuclei in the processing of simple auditory stimuli. In vivo extracellular single unit recordings were made from IC neurons in ketamine/xylazine anesthetized young adult F344 rats. When a unit was electrically isolated, the spontaneous activity level, characteristic frequency (CF) and CF threshold were determined. Rate/intensity functions (RIFs) in response to contralateral CF tones and to contralateral noise bursts were obtained as were tone isointensity functions. The recording site was marked by ejecting horseradish peroxidase (HRP) from an electrode. Locations of recorded units were determined from electrode track marks and HRP marks in serial brain sections. Recordings were made from 320 neurons in the IC; 176 were localized to the CIC and 87 to the ECIC. Thirteen percent of the units in each subdivision were found to be poorly responsive to auditory stimulation (clicks, tones or noise), and spontaneous activity was generally low. Characteristic frequencies representative of the full rat audiogram were found in each subdivision with the mean threshold significantly higher in the ECIC (28.7 dB SPL) than in the CIC (22.3 dB SPL). The mean maximum discharge rate to CF tone bursts was near 24 spikes/s in each subdivision. Dynamic range tended to be higher in the ECIC (28.3 dB) than in the CIC (23.2 dB), reflecting the lower percentage of nonmonotonic units found in the ECIC. Most units responded more robustly with a slower tone presentation rate, displayed lower levels of discharge to noise bursts than to tone bursts, and had differently shaped tone and noise RIFs. Most units were classified as onset responders to CF tone bursts in both subdivisions, with the percentage of onset responders higher in the ECIC (68.9%) than in the CIC (57.8%). First spike latency did not differ significantly between the subdivisions, but tended to be shorter in the CIC. The breadth of the excitatory receptive fields did not differ significantly between subdivisions, although the mean was slightly larger in the ECIC. These results are generally consistent with the results of CIC studies from other species, establishing the F344 rat as a model of CIC physiology. Differences between CIC and ECIC units included a higher percentage of nonmonotonic RIFs and lower percentage of onset temporal response patterns in the CIC than in the ECIC. Some properties which have been previously used as hallmarks for differentiation between CIC and ECIC units, namely broader tuning and longer first spike latencies in the ECIC, did not reach statistical significance in this study. These may reflect species differences and/or the highly variable and largely overlapping sets of responses evident in the large sample size used in this study.

Acoustic Stimulation↗

PubMed1996

GABA inputs control discharge rate primarily within frequency receptive fields of inferior colliculus neurons.

1. Recent studies have suggested that gamma-aminobutyric acid (GABA) inputs shape monaural and binaural neuronal response properties in the central nucleus of the inferior colliculus (CIC). CIC neurons receive major inhibitory GABAergic projections from intrinsic, commissural, and extrinsic sources. Many GABAergic projections now are thought to arise from cells that are tonotopically matched to their CIC targets. 2. We tested the hypothesis that GABA circuits are aligned primarily within the CIC target neuron's excitatory response area and therefore have their greatest effects on discharge rate mainly within that frequency domain. GABA inhibition was examined by recording families of isointensity contours before, during, and after GABAA receptor blockade. Iontophoretic application of bicuculline-methiodide (BMI) was used to block GABAA receptors. Quantitative measures of frequency bandwidth and z-score analysis of discharge rate within the excitatory receptive field were used to compare pre- and postdrug conditions. 3. Chinchilla CIC unit response properties were similar to those described for other species, with a high percentage of phasic temporal response patterns and nonmonotonic rate-intensity functions in response to monaural contralateral characteristic frequency (CF) tones. Binaural responses of most CIC neurons showed suppression of contralaterally evoked responses by ipsilateral stimulation. 4. For 85% of CIC neurons, blockade of GABAA inputs was found to increase discharge rate within the excitatory response area. Forty-five percent were classified as near-CF changes and 32% as near-CF and low side. Changes in lateral/flanking inhibition in the absence of near-CF changes were never observed. Forty-one percent of CIC neurons displayed less than a 10% increase in frequency bandwidth at 25-35 dB above threshold with BMI application. 5. These data suggest that GABA inhibition arises primarily from neurons with inhibitory fields aligned with their CIC targets. Thus the effect of the inhibition is primarily contained within or overlapping each target neuron's excitatory response area. CIC GABAergic circuits may function to adjust the gain needed for coding complex signals over a wide dynamic range.

Animals↗

PubMed1996

Physiology of the aged Fischer 344 rat inferior colliculus: responses to contralateral monaural stimuli.

1. Presbycusis, age-related hearing loss, is an ever increasing problem in our aging society. It involves changes in both the peripheral and central portions of the auditory system. The inferior colliculus (IC) has been shown to display age-related changes including decreased gamma-aminobutryic acid (GABA) levels, decreased glutamate decarboxylase levels, and decreased binding by GABAB receptors, as well as rearrangement of axon terminals in aging Fischer 344 (F344) rats. Age-related physiological changes have also been noted in the ICs of C57 and CBA mice. 2. Given the age-related alterations in the inhibitory neurotransmitter system, we hypothesized that aged F344 rats would show alterations in the physiological response properties of their IC neurons due to an imbalance in the relative levels of inhibition and excitation affecting the neuronal firing. 3. In vivo extracellular single-unit recordings were made from 297 IC neurons in ketamine/xylazine-anesthetized aged (24 mo) F344 rats. Locations of recorded units were determined from the electrode track marks and horseradish peroxidase marks. Results were compared with those obtained from young adult (3 mo) animals. 4. Average threshold increased from 25.4 dB SPL in young rats to 56.1 dB SPL in aged rats. 5. Although there was a reduction in the percentage of units recorded at either extreme of the frequency range in aged animals, the characteristic frequency (CF) range and mean did not differ between the two groups. 6. For the IC as a whole, no differences were noted in spontaneous activity, first spike latency, dynamic range, percentage of units with nonmonotonic contralateral CF tone rate/intensity functions (RIFs), or percentage of units sensitive to change in CF tone presentation rate. 7. In aged rats, a higher percentage of units was poorly responsive to auditory stimulation. 8. In the aged rat, there was a 12% reduction in the maximum discharge rate, a 12% increase in the percentage of units classified as onset in their temporal response pattern, and an 18% increase in the breadth of the isointensity functions at 30 dB above threshold. 9. Age-related changes in the central nucleus of the IC (CIC) frequently differed from those observed in the external cortex of the IC (ECIC). The percentage of units classified as having nonmonotonic contralateral tone RIFs decreased with age in the CIC but increased with age in the ECIC, and the percentage of units classified as onset in their temporal response pattern increased with age in the CIC but did not change with age in the ECIC. 10. The results of this study support the hypothesis that there is an age-related shift to higher intensities in the working range of most CIC units along with a small, selective deficit in inhibitory processing. When considered in conjunction with the mouse aging studies conducted by other researchers and with the results of a similar study of single units in the visual system (lateral geniculate nucleus) of young and aged rhesus monkeys, these results suggest that compensatory mechanisms are highly active in sensory systems as animals age. Despite deficits that lead to reduced input to the IC and neurochemical changes affecting neurotransmitter levels, IC neurons in aged rats are able to respond to most simple auditory stimuli in a fashion quite similar to that observed in young rats.

Age Factors↗

PubMed1995

Age-related reduction of [3H]strychnine binding sites in the cochlear nucleus of the Fischer 344 rat.

The present study used quantitative receptor autoradiography to examine the effects of aging on the binding profile of the strychnine-sensitive glycine receptor in the Fischer 344 rat. Glycine receptor binding sites were localized using [3H]strychnine in two principal subdivisions of the cochlear nucleus; the dorsal and anteroventral cochlear nucleus. These central auditory brainstem structures are known to receive extensive glycinergic inputs. In young rats, single concentrations of [3H]strychnine showed significantly higher binding levels in the dorsal cochlear nucleus than the anteroventral cochlear nucleus (+38%, P < 0.001). Little binding was detected in regions of the posteroventral cochlear nucleus, and no specific binding was apparent in the cerebellum. Saturation analysis in the dorsal cochlear nucleus revealed an affinity constant (Kd) of 16.9 nM and a maximum number of binding sites of 850 fmol/mg protein. A significant age-related decrease in [3H]strychnine (8 nM) binding was observed in the anteroventral cochlear nucleus (-37%, P = 0.003) and dorsal cochlear nucleus (-23%, P = 0.034) of 26-month-old rats compared with three-month-old rats. Saturation analysis indicated that the observed decrease in binding was due to a decrease in the total number of binding sites with no significant change in affinity. In the dorsal cochlear nucleus, the number of binding sites was reduced (-26%) in 26-month-old rats compared with three-month-old adults (P = 0.011). Kd was decreased (-22%) in 26-month-old rats when compared with young adults, but this decrease was not statistically significant (P = 0.377).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗