Donald Gans

Glycinergic “Inhibition” Mediates Selective Excitatory Responses to Combinations of Sounds

In the mustached bats inferior colliculus (IC), combination-sensitive neurons display time-sensitive facilitatory interactions between inputs tuned to distinct spectral elements in sonar or social vocalizations. Here we compare roles of ionotropic receptors to glutamate (iGluRs), glycine (GlyRs), and GABA (GABAARs) in facilitatory combination-sensitive interactions. Facilitatory responses to 36 single IC neurons were recorded before, during, and after local application of antagonists to these receptors. The NMDA receptor antagonist CPP [(±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid], alone (n = 14) or combined with AMPA receptor antagonist NBQX (n = 22), significantly reduced or eliminated responses to best frequency (BF) sounds across a broad range of sound levels, but did not eliminate combination-sensitive facilitation. In a subset of neurons, GABAAR blockers bicuculline or gabazine were applied in addition to iGluR blockers. GABAAR blockers did not “uncover” residual iGluR-mediated excitation, and only rarely eliminated facilitation. In nearly all neurons for which the GlyR antagonist strychnine was applied in addition to iGluR blockade (22 of 23 neurons, with or without GABAAR blockade), facilitatory interactions were eliminated. Thus, neither glutamate nor GABA neurotransmission are required for facilitatory combination-sensitive interactions in IC. Instead, facilitation may depend entirely on glycinergic inputs that are presumed to be inhibitory. We propose that glycinergic inputs tuned to two distinct spectral elements in vocal signals each activate postinhibitory rebound excitation. When rebound excitations from two spectral elements coincide, the neuron discharges. Excitation from glutamatergic inputs, tuned to the BF of the neuron, is superimposed onto this facilitatory interaction, presumably mediating responses to a broader range of acoustic signals.

Contribution of NMDA and AMPA Receptors to Temporal Patterning of Auditory Responses in the Inferior Colliculus

Although NMDA receptors (NMDARs) are associated with synaptic plasticity, they form an essential part of responses to sensory stimuli. We compared contributions of glutamatergic NMDARs and AMPA receptors (AMPARs) to auditory responses in the inferior colliculus (IC) of awake, adult mustached bats. We examined the magnitude and temporal pattern of responses to tonal signals in single units before, during, and after local micro-iontophoretic application of selective antagonists to AMPARs [NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide)] and NMDARs [CPP ((±)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid)]. Combined blockade of AMPARs and NMDARs eliminated excitatory responses in nearly all neurons, whereas separate blockade of each receptor was quantitatively similar, causing substantial (>50%) spike reductions in ∼75% of units. The major result was that effects of receptor blockade were most closely related to the first-spike latency of a unit. Thus, AMPAR blockade substantially reduced spikes in all short-latency units (<12 ms) but never in long-latency units (≥12 ms). NMDAR blockade had variable effects on short-latency units but reduced spikes substantially for all long-latency units. There were no distinct contributions of AMPARs and NMDARs to early and late elements of responses. Thus, AMPAR blockade reduced early (onset) spikes somewhat more effectively than NMDAR blockade in short-latency units, but NMDAR blockade reduced onset spikes more effectively in long-latency units. AMPAR and NMDAR blockade were equally effective in reducing later elements of sustained responses in short-latency units, whereas NMDAR blockade was much more effective in long-latency units. These results indicate that NMDARs play multiple roles for signal processing in adult IC neurons.

Intracellular Recordings From Combination-Sensitive Neurons in the Inferior Colliculus

In vertebrate auditory systems, specialized combination-sensitive neurons analyze complex vocal signals by integrating information across multiple frequency bands. We studied combination-sensitive interactions in neurons of the inferior colliculus (IC) of awake mustached bats, using intracellular somatic recording with sharp electrodes. Facilitated combinatorial neurons are coincidence detectors, showing maximum facilitation when excitation from low- and high-frequency stimuli coincide. Previous work showed that facilitatory interactions originate in the IC, require both low and high frequency-tuned glycinergic inputs, and are independent of glutamatergic inputs. These results suggest that glycinergic inputs evoke facilitation through either postinhibitory rebound or direct depolarizing mechanisms. However, in 35 of 36 facilitated neurons, we observed no evidence of low frequency-evoked transient hyperpolarization or depolarization that was closely related to response facilitation. Furthermore, we observed no evidence of shunting inhibition that might conceal inhibitory inputs. Since these facilitatory interactions originate in IC neurons, the results suggest that inputs underlying facilitation are electrically segregated from the soma. We also recorded inhibitory combinatorial interactions, in which low frequency sounds suppress responses to higher frequency signals. In 43% of 118 neurons, we observed low frequency-evoked hyperpolarizations associated with combinatorial inhibition. For these neurons, we conclude that low frequency-tuned inhibitory inputs terminate on neurons primarily excited by high-frequency signals; these inhibitory inputs may create or enhance inhibitory combinatorial interactions. In the remainder of inhibited combinatorial neurons (57%), we observed no evidence of low frequency-evoked hyperpolarizations, consistent with observations that inhibitory combinatorial responses may originate in lateral lemniscal nuclei.

Suppression of drinking following rotational stimulation as an index of motion sickness in the rat

A suppression-of-drinking measure was used as an index of the duration and magnitude of rotation-elicited UCR. Thirsty rats suppressed drinking when they were rotated prior to being given access to water. The magnitude of suppression increased as a function of the duration of intermittent rotation. Periodically interrupted rotation sessions were found to suppress drinking for longer periods than continuous rotation sessions of comparable duration. Damage to the vestibular system substantially decreased the magnitude of suppression of drinking following rotation and prevented the acquisition of rotation-induced taste aversion. The failure of rotation-induced taste aversion to develop in rats sustaining vestibular damage was not attributable to an associative/sensory deficit as these rats acquired the aversion when lithium chloride poisoning was used as the UCS.

Temporal features of spectral integration in the inferior colliculus: effects of stimulus duration and rise time.

This report examines temporal features of facilitation and suppression that underlie spectrally integrative responses to complex vocal signals. Auditory responses were recorded from 160 neurons in the inferior colliculus (IC) of awake mustached bats. Sixty-two neurons showed combination-sensitive facilitation: responses to best frequency (BF) signals were facilitated by well-timed signals at least an octave lower in frequency, in the range 16-31 kHz. Temporal features and strength of facilitation were generally unaffected by changes in duration of facilitating signals from 4 to 31 ms. Changes in stimulus rise time from 0.5 to 5.0 ms had little effect on facilitatory strength. These results suggest that low frequency facilitating inputs to high BF neurons have phasic-on temporal patterns and are responsive to stimulus rise times over the tested range. We also recorded from 98 neurons showing low-frequency (11-32 kHz) suppression of higher BF responses. Effects of changing duration were related to the frequency of suppressive signals. Signals<23 kHz usually evoked suppression sustained throughout signal duration. This and other features of such suppression are consistent with a cochlear origin that results in masking of responses to higher, near-BF signal frequencies. Signals in the 23- to 30-kHz range-frequencies in the first sonar harmonic-generally evoked phasic suppression of BF responses. This may result from neural inhibitory interactions within and below IC. In many neurons, we observed two or more forms of the spectral interactions described here. Thus IC neurons display temporally and spectrally complex responses to sound that result from multiple spectral interactions at different levels of the ascending auditory pathway.

Observer bias in the hearing testing of profoundly involved multiply handicapped children.

Observer bias was investigated using 27 profoundly involved multiply handicapped children and behavioral observation audiometry. Two observers were in the room with the child, two others viewed via a video monitor, and each of the four observers had full knowledge of stimulus-type and intensity. Two additional observers viewed a videotape without being provided information about the stimuli. Results showed clear bias effects in 85% of the children. At low intensities, observers aware of stimulus events tended to score fewer responses than those judges unaware of stimulus intensity. At high levels, this trend was reversed. It is recommended that the estimation of hearing threshold in handicapped children be made by observers who do not have access to the sequence of stimulus presentations.

Bias in scoring auditory brainstem responses

ABR waveforms from 50 multi-handicapped children were analysed by nine judges in an investigation of scoring bias. Prior to estimating threshold for each subject, the judges were provided with either true or false ABR thresholds. This preliminary information was true in 25 of the cases and false in the other 25. The same ABR waveforms were evaluated one week later, but true/false biasing thresholds were reversed. Results revealed that while the more experienced judges were more accurate in their assessments, they were not necessarily less biased. The effects of bias were more predominant in those cases where the estimation of threshold was the most difficult.

Effects of artifact rejection and bayesian weighting on the auditory brainstem response during quiet and active behavioral conditions.

PURPOSE To evaluate the effects of 2 noise reduction techniques on the auditory brainstem response (ABR). METHOD ABRs of 20 normal hearing adults were recorded during quiet and active behavioral conditions using 2 stimulus intensity levels. Wave V amplitudes and residual noise root-mean-square values were measured following the offline application of artifact rejection and Bayesian weighting. Repeated measures analysis of variance and Bonferroni adjusted pairwise t tests were utilized to evaluate significant main effects and interactions between the 2 noise reduction techniques. RESULTS ABRs recorded during the quiet behavioral condition resulted in minimal differences in wave V amplitude and noise reduction improvement, suggesting that the 2 techniques were equally effective under ideal recording situations. During the active behavioral condition, however, the techniques differed significantly in the ability to preserve the evoked potential and reduce noise. Consequently, strict artifact rejection levels resulted in an inherent underestimation of wave V amplitudes when compared with the Bayesian approach. CONCLUSION Artifact rejection had a detrimental effect on waveform morphology of the ABR. This could lead to difficulty in ABR interpretation when patients are active and ultimately result in diagnostic errors.

Development of a hearing test protocol for profoundly involved multi-handicapped children.

ABSTRACT The purpose of the present study was to develop a protocol for use in testing the hearing of profoundly involved multi-handicapped children. Behavioral observation audiometry, visual reinforcement audiometry, auditory brain stem response (ABR], and noise tone difference tests were administered to 156 children with multiple handicaps. Eighty three percent of the children with normal middle ear function were estimated to haw normal heaping or, at worst, a mild hearing loss, by one or more of the tests. ABR was the single best test, followed by behavioral observation audiometry and noise tone difference. However, only 65% of the children would have passed had they only been tested with ABR. If agreement among two of the tests had been required, hearing loss would have been ruled out in only 34% of the children. A factor analysis revealed that the various hearing tests were associated with different medical and physical conditions which might influence threshold estimation for multi-handicapped children. These results support use of a series positive test battery protocol in which individual tests are used sequentially with the purpose of ruling out moderate-profound sensorineural hearing loss.

Auditory-evoked response morphology in profoundly-involved multi-handicapped children: comparisons with normal infants and children.

The developmental and difference/defect theories have been used to explain auditory development in some multi-handicapped children. If developmental factors influence auditory response behaviors, it might be predicted that evoked potentials measured from the central auditory nervous system would reflect similar developmental influences in multi-handicapped children. The purpose of this study was to compare auditory-evoked-potential waveform morphology between profoundly-involved multi-handicapped children and normal infants and children. Auditory brainstem response (ABR) and middle-latency response (MLR) morphology were examined from waveform descriptions, wave detection, latency, amplitude, and spectral energy measures. The majority of handicapped subjects exhibited response morphology unlike that of normal children or infants. ABR/MLR morphology for handicapped children was characterized by depressed responses and substantial waveform variability. The results of this study tended to support the difference/defect theory.