Biomedical subjects

D M Caspary

Publications and source records attributed to D M Caspary.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1994

Age-related changes in brainstem auditory neurotransmitters: measures of GABA and acetylcholine function.

This study was designed to determine if there are age-related alterations in the bio-synthetic enzyme glutamic acid decarboxylase (GAD), the degradative enzyme GABA-transaminase (GABA-T), and the uptake system for GABA in the central nucleus of the inferior colliculus (CIC), the cochlear nucleus (CN), and/or nuclei of the lateral lemniscus (NLL) of Fischer-344 rats. For purposes of comparison, the cholinergic neuronal system was studied in parallel in young adult (3-7 months), mature (15-17 months) and aged (24-26 months) rats. In young adults GAD activity was highest in the CIC (219 nmol/mg protein/h; N = 5), intermediate in NLL (82 nmol/mg protein/h), and lowest in CN (34 nmol/mg protein/h). Choline acetyltransferase (ChAT) activity was highest in NLL and CN, and approximately 35-40% lower in CIC. A more uniform pattern was observed with GABA-T activity. Reductions in GAD activity were seen in the CIC of mature (-31%) and aged (-30%) rats that were not graded with age when compared to young adult, P < 0.05 (N = 5). This effect was regionally selective, since the CN did not show any loss of GAD or ChAT activity. The neurotransmitter selectivity of this deficit in CIC is supported by the non-parallel changes in ChAT activity (-22%, aged vs. mature, P < 0.05) that occurred after the changes in GAD activity. In contrast to the loss of GABAergic biosynthetic capacity in aged CIC, high affinity uptake processes (Kd and Vmax) for 14C-GABA and 3H-D-aspartate were not significantly altered (P > 0.05). Similar to the CIC, the NLL showed remarkable age-related deficits, but these deficits were more substantial for the cholinergic system (ChAT activity: -56% aged vs. young adult, P < 0.05; GAD activity: -35% aged vs. mature). None of the areas examined showed a significant loss of GABA-T activity with aging. These data suggest: 1) Age-related loss of GABA-mediated inhibition in the CIC of Fischer-344 rats is not attributable to changes in uptake or degradation of GABA, but may be related loss of biosynthetic capacity (i.e. activity or quantity) of the GAD present; 2) processing centers of the central auditory pathway (i.e. CIC and NLL), but not necessarily primary (i.e. CN) integrative nuclei, demonstrate selective, age-related neurochemical deficits; and 3) age-related neurochemical changes in central auditory structures may contribute substantially to the abnormal perception of signals in noise and loss of speech discrimination observed in neural presbycusis.

4-Aminobutyrate Transaminase↗

PubMed1994

Paired tone facilitation in dorsal cochlear nucleus neurons: a short-term potentiation model testable in vivo.

It has been suggested that the dorsal cochlear nucleus (DCN) is involved in coding stimulus history or prior auditory activity [Manis (1989) J. Neurophys., 61, 149-161; Manis (1990) J. Neurosci., 10, 2338-2351]. The major output neurons of the DCN are the fusiform (pyramidal) cells which are thought to receive excitatory inputs from the descending branch of the acoustic nerve onto their basal dendrites and significant inhibitory glycinergic and GABAergic inputs to the soma and dendrites. The apical dendrites of these neurons lie within the molecular layer of the DCN and encounter parallel fibers which are thought to utilize the excitatory amino acid neurotransmitter glutamate. In this study of anesthetized chinchillas, we found that, in contrast to the responses of acoustic nerve fibers and most cochlear nucleus neurons which are masked by an appropriate preceding signal, many DCN principal cells are facilitated during the second of two identical stimuli. Facilitated DCN responses often have a reduced interspike interval and a more chopper-like temporal response pattern to the second characteristic frequency tone. This paired tone facilitation in the chinchilla DCN provides as in vivo model of short-term potentiation elicited by sensory stimulation similar to the paired-pulse facilitation observed with electrical stimulation in other models.

Acoustic Stimulation↗

PubMed1994

Age-related changes in auditory brainstem responses in Fischer 344 rats: effects of rate and intensity.

Age-related changes in auditory brainstem responses (ABR) observed in humans may reflect peripheral or centrally-occurring deficits. In clinical studies, high stimulus repetition rates have been used to improve the identification of central auditory pathology. In the present study, interactions between stimulus level and repetition rate were examined in the Fischer 344 rat, an animal demonstrating both peripheral hearing loss and changes in auditory brainstem neurochemistry with age. Monaural threshold and standard ABR morphology were determined in young (3-6 months) and old (20-23 months) rats using clicks at 10/s, with intensity varied from 0-100 dB. The effects of increasing stimulus repetition rate on ABR latency and morphology were evaluated at 60-100 dB using rates of 5, 10, 20, and 40/s. Old animals demonstrated elevated ABR click thresholds, reflected by shifts in the latency-intensity curves. With increased stimulation rates, aged rats exhibited prolonged Wave 4 and 5 latencies, especially at the highest intensities, with degraded waveform morphology. Peak amplitudes were generally reduced in old rats, irrespective of rate or stimulus level. These findings suggest auditory processing is altered in aged animals, while the selective effects of rate increases on Waves 4 and 5 provide supporting evidence for possible involvement of the central auditory generators of these components.

Acoustic Stimulation↗

PubMed1994

Loss of synaptic inhibition during repetitive stimulation in genetically epilepsy-prone rats (GEPR).

Genetically epilepsy-prone rats (GEPR) are an animal model of generalized motor seizures. The underlying causes of the predisposition to seizures in GEPR have not been fully determined. The brainstem auditory system is critical for audiogenic seizures in GEPR, and neurophysiological abnormalities have been observed in these areas, but recent evidence suggests that non-auditory brain areas may also be abnormal. This may account for the lowered threshold in GEPR for various non-audiogenic seizures. Because the normal responses of the hippocampal Schaffer collateral/CA1 synapse are relatively well understood, we studied single and repetitive synaptic responses in hippocampal slices of GEPR in vitro. Our hypothesis was that altered excitatory or inhibitory synaptic transmission may contribute to GEPR non-audiogenic seizure predisposition. We recorded extracellular EPSPs, population spikes, and afferent volleys in hippocampal area CA1, and compared GEPR responses to those of Sprague-Dawley (SD) rats, the strain from which GEPR were derived. GEPR responses to single synaptic stimuli were not significantly different from SD. The second of a pair of closely spaced EPSPs or population spikes was larger in both GEPR and SD (paired pulse facilitation), but the magnitude of population spike facilitation was significantly increased in GEPR. Short trains of four stimuli caused inhibition of population spike firing in SD, an effect that was much reduced in GEPR. When SD slices were treated with bicuculline, a GABAA receptor antagonist, enhanced paired pulse facilitation and loss of inhibition during trains of stimuli were seen, similar to the patterns seen in GEPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1994

Inhibitory inputs modulate discharge rate within frequency receptive fields of anteroventral cochlear nucleus neurons.

1. The amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine function as inhibitory neurotransmitters associated with nonprimary inputs onto spherical bushy and stellate cells, two principal cell types located in the anteroventral cochlear nucleus (AVCN). These neurons are characterized by primary-like (including phase-locked) and chopper temporal response patterns, respectively. 2. Inhibition directly adjacent to the excitatory response area has been hypothesized to sharpen or limit the breadth of the tonal frequency receptive field. This study was undertaken to test whether GABA and glycine circuits function primarily to sharpen the lateral edges of the tonal excitatory response area or to modulate discharge rate within central portions of the excitatory response area of AVCN neurons. 3. To test this, iontophoretic application of the glycineI antagonist, strychnine, or the GABAA antagonist, bicuculline, was used to block inhibitory inputs after obtaining control families of isointensity contours (response areas) from extracellularly recorded AVCN neurons. 4. Blockade of GABA and/or glycine inputs was found to increase discharge rate primarily within the excitatory response area of neurons displaying chopper and primary-like temporal responses with little or no change in bandwidth or in off-characteristic frequency (CF) discharge rate. 5. The principal sources of inhibitory inputs onto AVCN neurons are cells located in the dorsal cochlear nucleus and superior olivary complex, which appear to be tonotopically matched to their targets. In agreement with these morphological studies, the data presented in this paper suggest that most GABA and/or glycine inhibition is tonotopically aligned with excitatory inputs. 6. These findings support models that suggest that GABA and/or glycine inputs onto AVCN neurons are involved in circuits that adjust gain to enable the detection of signals in noise by enhancing signal relative to background.

Animals↗

PubMed1994

Scanning electron microscopic evaluation of age-related changes in the rat vestibular epithelium.

An ultrastructural study was performed to assess age-related changes in the vestibular end organs of Fischer 344 rats. The surfaces of the maculae and cristae from 3-, 12-, and 24-month-old Fischer 344 rats were observed by use of scanning electron microscopy. Age-related changes in the morphology of the vestibular neuroepithelium included a substantial loss of hair cells, as well as a reduction in the number of kinocilia and stereocilia on those that remained. These changes were greatest in the central upper regions of the three ampullae. In aged animals a greater area of the neuroepithelial surface was covered with microvilli, and in some instances, giant cilia were found among the microvillous surfaces. In contrast, there were few differences among the three age groups in the number and condition of hair cells in the saccules and utricles. The changes observed in the cristae may contribute to the age-associated impairment of vestibular function. If similar changes occur in human beings, these could in part account for the presbycusis observed in the elderly.

Acoustic Maculae↗

PubMed1992

GABAA receptor antagonist bicuculline alters response properties of posteroventral cochlear nucleus neurons.

1. The role of GABAergic inhibitory inputs onto posteroventral cochlear nucleus (PVCN) neurons in the anesthetized chinchilla was investigated through iontophoretic application of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline. The majority of the neurons studied displayed phasic temporal response patterns. 2. All the neurons were sensitive to bicuculline and displayed an increase in discharge rate, which was greatest during the post-onset portion of the response. Most of the tested neurons were also sensitive to muscimol, which appeared to mimic the putative effect of endogenous GABA. 3. Bicuculline reduced the average first-spike latency and the average variability of the first-spike latency. Muscimol had the opposite effect. 4. Bicuculline did not significantly alter the threshold but rather increased discharge rate at suprathreshold intensities. 5. The width of the excitatory response area was not significantly increased by application of bicuculline. The increase in discharge rate occurred within the units' excitatory response areas. 6. The shape of the rate-intensity functions was not altered by bicuculline application. 7. We conclude that GABAergic inhibitory inputs control the post-onset discharge rate of some PVCN neurons. They may suppress tonic activity, resulting in more phasic discharge patterns.

Acoustic Stimulation↗

PubMed1991

Involvement of GABA in acoustically-evoked inhibition in inferior colliculus neurons.

Most criteria for establishing GABA as an inhibitory neurotransmitter in the central nucleus of inferior colliculus (ICc) have been satisfied, but the role of GABA in acoustic coding in ICc is not established. The present study examined this issue by evaluating the effects of iontophoretic application of agents that alter activity at GABA receptors on potential forms of acoustically-evoked inhibition in ICc neurons. Application of the GABAA antagonist, bicuculline, selectively blocked the firing reduction at high intensities observed during non-monotonic rate-intensity functions in ICc neurons. Binaural inhibition was selectively blocked by bicuculline and increased by nipecotic acid. Application of GABA, nipecotic acid (GABA uptake inhibitor) and a benzodiazepine (flurazepam), which enhances the action of GABA, increased the duration and intensity of ipsilateral inhibition and response pause, while bicuculline blocked these acoustically-evoked inhibitory events. Offset inhibition was increased by nipecotic acid application and reduced by bicuculline with the appearance of an offset peak. The present data support an important role for GABA as a neurotransmitter, mediating, in part, non-monotonicity, binaural inhibition, response pause and offset inhibition in ICc neurons. Alterations of these GABA-mediated inhibitory phenomena may occur in auditory dysfunctions observed with aging and audiogenic seizures.

Acoustic Stimulation↗

PubMed1991

Low-frequency neurons in the lateral superior olive exhibit phase-sensitive binaural inhibition.

1. Responses of low characteristic frequency (CF) neurons in the lateral limb of the lateral superior olive (LSO) of chinchilla and rat to binaural stimuli at various interaural phase and intensity differences were examined and compared to responses from previous studies of high CF neurons. 2. Ninety-six LSO neurons from chinchillas and 10 LSO neurons from rats with CFs less than 1,200 Hz were characterized. The majority of these neurons displayed phase-locked tone-evoked temporal discharge patterns to ipsilateral CF stimuli. 3. Similar to high-CF LSO neurons, low-CF LSO neurons were excited by ipsilateral stimuli and inhibited by contralateral stimuli, with discharge rate sensitive to interaural intensity differences (IID). Discharge rate increased as ipsilateral intensity was increased and decreased as contralateral stimulus intensity was increased. 4. Binaural inhibition, inhibition of ipsilaterally evoked activity by contralateral stimuli, was dependent on interaural phase differences (IPD) in the majority of low-CF LSO neurons. Responses of phase-sensitive neurons to binaural stimuli often varied with 90 or 180 degrees changes in IPD from total inhibition to a facilitated response when compared to responses to control ipsilateral stimuli alone. 5. In summary, like high-CF LSO neurons, LSO neurons with low CFs (less than 1,200 Hz) were ipsilaterally excited and contralaterally inhibited (EI) and were sensitive to IID. Unlike most high-CF EI LSO neurons, which are not responsive when the azimuth of the stimulus is directly in front of or directly behind the animal, many low-CF LSO neurons are responsive to these stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis.

The present study describes substantial, selective, age-related loss of the putative inhibitory neurotransmitter GABA in the central nucleus of the inferior colliculus (CIC) of rat based on immunocytochemical and neurochemical data. For immunocytochemistry, neurons in the CIC were immunolabeled using an antibody against a GABA conjugate in young adult (2- to 7-month-old) and aged (18- to 29-month-old) Fischer-344 rats. Computer-assisted morphometry was then used to generate maps of GABA-immunoreactive neurons in the CIC. The number of GABA-positive neurons was reduced 36% in the ventrolateral portion of the CIC of aged animals (93 neurons/mm2) compared to their matched young adult cohorts (145 neurons/mm2; p less than 0.01). For neurochemistry, basal and K(+)-evoked release of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals from the 2 age groups using high-performance liquid chromatography. Overflow of radiolabeled acetylcholine (3H-ACh) was also determined. In both age groups, K(+)-evoked release of GABA, Glu, Asp, and 3H-ACh from CIC punches was significantly enhanced above basal efflux (+200, +215, +163, and +309%, respectively), while Tyr release was unchanged. Evoked release of 3H-ACh and all amino acids except Tyr showed substantial Ca2+ dependence. A significant (p less than 0.05) age-related reduction in both basal (-35%) and K(+)-stimulated (-42%) efflux of GABA from the CIC was observed. A corresponding decrease in postrelease tissue content of GABA in CIC of aged rats was observed (-30%, p less than 0.05). In contrast, tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh was similar between the 2 age groups. Age-related GABA neurochemical changes described in the CIC were not observed in the release of the other amino acids or 3H-ACh from either the rostral ventrolateral medulla or the somatosensory cortex, 2 brain regions involved in processing non-auditory sensory input. These data support previous findings that GABA, Glu, Asp, and ACh may subserve neurotransmission in the CIC. Additionally, these data provide clear evidence for a pronounced, region- and neurotransmitter-selective, age-related reduction of GABA in the CIC. These findings support the hypothesis that impairment of inhibitory GABAergic neurotransmission in the CIC may contribute to abnormal auditory perception and processing seen in neural presbycusis.

Acetylcholine↗

PubMed1989

Non-N-methyl-D-aspartate receptors may mediate ipsilateral excitation at lateral superior olivary synapses.

Principal cells of the lateral superior olivary nucleus (LSO) are thought to receive a direct excitatory input from spherical bushy cells located in the ipsilateral ventral cochlear nucleus (VCN) and an indirect input from the contralateral VCN globular bushy cells via a secure synapse in the medial nucleus of the trapezoid body (MNTB). MNTB bushy cells project to the somata and proximal dendrites of LSO principal cells. LSO neurons display phasic 'chopper' temporal response patterns to ipsilateral tone-burst stimuli at characteristic frequency (CF), while binaural stimuli suppress this ipsilaterally evoked activity. This suppression is sensitive to interaural differences in intensity, phase and time, suggesting a role for these neurons in the localization of sound in space. In the present study, the nature of the neurotransmitter mediating fast ipsilateral excitation of LSO neurons was examined using iontophoretic application of excitant amino acid (EAA) agonists and antagonists. N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) were used as agonists, while the selective NMDA receptor antagonist D. L-2-amino-5-phosphonovaleric acid (APV), and the non-selective receptor EAA antagonist cis-2,3-piperidine-dicarboxylic acid (PDA) were used to study ipsilaterally evoked neuronal responses. In 3 additional experiments the selective non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) replaced PDA. Ipsilateral, tone-evoked and spontaneous activities were generally enhanced by EAA agonists while partial blockade of tone-evoked, ipsilateral excitation was observed with EAA antagonists. Both PDA and DNQX more effectively blocked ipsilateral tone-evoked excitations and spontaneous activity than did the NMDA-receptor antagonist, APV.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

PubMed1989

On the role of GABA as an inhibitory neurotransmitter in inferior colliculus neurons: iontophoretic studies.

Significant neurochemical, immunocytochemical, and ligand binding studies support a role for GABA as an inhibitory neurotransmitter in the inferior colliculus (IC). The present study attempted to satisfy some of the remaining criteria for establishing transmitter identity by utilizing iontophoretic application onto IC neurons of agents affecting the action of gamma-aminobutyric acid (GABA). The agents examined include GABA, a GABAB agonist (baclofen), a GABAA antagonist (bicuculline), a GABA uptake inhibitor (nipecotic acid), and a benzodiazepine (flurazepam), thought to exert its actions on the GABA receptor complex. Application of GABA results in inhibition of the spontaneous firing and acoustically evoked responses of inferior colliculus neurons. The inhibitory effect of GABA is enhanced by the simultaneous application of nipecotic acid or flurazepam. These agents as well as baclofen produce firing reductions when applied alone in higher doses. The effect of GABA can be blocked by application of bicuculline, and acoustically evoked (binaural) inhibition can also be selectively blocked by low doses of this GABAA antagonist. These data along with previous studies utilizing different techniques fulfill many of the criteria for establishment of GABA as an important inhibitory transmitter in the inferior colliculus.

Acoustic Stimulation↗

PubMed1989

Effects of excitant amino acids on acoustic responses of inferior colliculus neurons.

Iontophoretic application of the excitant amino acids (EAAs), glutamate, aspartate and N-methyl-D-aspartate (NMDA) resulted in increased acoustically evoked and spontaneous firing of most neurons in the central nucleus of inferior colliculus (ICC). The excitatory effects of these EAAs were blocked by simultaneous application of EAA antagonists which selectively block the NMDA receptor subtype, 2-amino-5-phosphonovalerate or D-alpha-aminoadipate and to a lesser extent with non-selective EAA antagonists, such as glutamic acid diethylester. Application of NMDA receptor-selective EAA antagonists alone greatly reduced the firing of most ICC neurons examined, but non-selective EAA antagonists either increased or produced little change in firing of most ICC neurons examined. In this and previous studies cholinergic agonists were found to increase the firing of ICC neurons, but the cholinergic agonists were less effective in exciting ICC neurons than EAA agonists. Cholinergic antagonists in a previous study were considerably less effective in inhibiting the discharge of ICC neurons than were the EAA antagonists in the present study. These results, in conjunction with previous neurochemical and anatomical localization studies, support a possible role of an EAA as a candidate for afferent excitatory transmitter in neurons of the inferior colliculus.

2-Amino-5-phosphonovalerate↗

PubMed1989

Synaptic potentials of chinchilla lateral superior olivary neurons.

Neurons in the lateral superior olive (LSO) were characterized in vivo, by extracellular and intracellular recordings. Principal neurons of the LSO are excited by ipsilateral auditory stimuli and exhibit binaural inhibition, as observed in extracellular recordings. In subsequent intracellular recordings, ipsilateral acoustic stimuli evoked robust excitatory postsynaptic potentials (epsps), while contralateral stimuli evoked large inhibitory postsynaptic potentials (ipsps). The contralaterally evoked ipsps were reversed when the cell was polarized below resting membrane potential and when current was injected into neurons recorded with chloride-filled electrodes. The ipsp is probably a reflection of contralaterally evoked release of glycine acting through glycinergic receptors on the somata and proximal dendrites of these neurons. The properties of the epsps are consistent with data suggesting that ipsilaterally evoked excitation may be mediated by an excitatory amino acid-like substance acting through quisqualate or kainate receptors at dendritic locations.

Amino Acids↗

PubMed1989

Presbycusis.

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Aged↗