Thermal effects on the vestibular hair cell synapse have to be considered for the explanation of caloric nystagmus.
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Biomedical subjects
Publications and source records attributed to R Klinke.
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The structure of human interleukin 4 (IL-4) was predicted utilizing a series of experimental and theoretical techniques. Circular Dichroism (CD) spectroscopy indicated that IL-4 belonged to the all alpha-helix class of protein structures. Secondary structure prediction, site-directed mutagenesis, and CD spectroscopy suggested a predominantly alpha-helical structure, consistent with a four-helix bundle structural motif. A human/mouse IL-4 chimera was constructed to qualitatively evaluate alternative secondary structure predictions. The four predicted helices were assembled into tertiary structures using established algorithms. The mapping of three disulfide bridges in IL-4 provided additional constraints on possible tertiary structures. Using accessible surface contact area as a criterion, the most suitable structures were right handed all antiparallel four-helix bundles with two overhand loop connections. Successful loop closure and incorporation of the three disulfide constraints were possible while maintaining the expected shape, solvent accessibility, and steric interactions between loops and helices. Lastly, energy minimization was used to regularize the chain.
Unilaterally deafened (cochlear destruction) gerbils were exposed to white noise after injection of 14-C-2-deoxyglucose. The labelling patterns were compared to those of unstimulated operated animals, noise stimulated control animals and bilaterally ear plugged animals. Serial transverse, horizontal and tangential autoradiographs through the cortex were analysed. In lesioned animals, labelling was strongly reduced on the side contralateral to the lesion in the high frequency regions of A1 and the anterior auditory field (AAF). We assume that these regions correspond to the high frequency EI cell areas. Fine banding could be seen superimposed on this pattern in transverse and tangential sections. We suggest that this may be due to alternating strips of EI and EE cells orthogonal to iso-frequency contours. In the low frequency regions of A1 and AAF, labelling asymmetries were also present, but were less pronounced. We assume that these effects are due to low frequency EE cells. In sub-cortical structures, labelling was reduced in the inferior colliculus and ventral part of the medial geniculate body contralateral to the lesioned ear, but no labelling pattern was visible. We presume that the spatial separation of EE and EI inputs to these structures is not marked enough to allow labelling patterns to be seen. In the superior olivary complex, labelling was reduced on the side contralateral to the lesioned ear in the medial dendritic field of the medial superior olivary nucleus and in the nucleus of the trapezoid body. Ipsilateral to the lesioned ear, labelling was reduced in the lateral dendritic field of the medial superior olive.
Hyaline cells of the auditory organ of the spectacled caiman contain smooth muscle-like filament bundles within their basal cell pole. These bundles were heavily labeled with antibodies to actin, myosin and alpha-actinin (muscular Z-line protein). Since hyaline cells are firmly attached to the basilar membrane these cells may actively modify the stiffness of the basilar membrane. A contractile mechanism in hyaline cells might affect frequency tuning of primary auditory afferents. This frequency tuning has been shown to be a temperature-dependent process in caimans and other submammalian species. The presence of synaptic contacts between efferent nerve fibres and hyaline cells suggests neural control of hyaline cell activity.
The endocochlear potential (EP) in the pigeon ear was altered by injecting current into the scala media. Simultaneous recordings from afferent fibres in the cochlear ganglion were performed. The mean rate of spontaneous activity was little affected by current injection and the consequent shifts in EP. In contrast to this lack of effect, the preferred intervals seen in some fibres in birds were accentuated by positive current injection and reduced or in some cases suppressed by negative current injection. The threshold of the tuning curve was raised by injection of negative current but the characteristic frequency showed little change. Sharpness of tuning decreased. Analysis of the results shows that current injection in the scala media produces significant changes in the filter characteristics of the cochlea, as well as altering the driving force for the transduction process (difference between EP and hair cell membrane potential).
A previously unknown sensory epithelium can be found on the medial wall of the apical part of the pigeon cochlear duct. It comprises about 200 hair cells. These are not arranged in any regular pattern, shape and orientation of the ciliary bundles even differ in neighbouring hair cells. We therefore propose the term papilla chaotica.
The cochlear ganglion of the pigeon contains neurones sensitive to sound frequencies below 20 Hz (infrasound). They are characterized by a high spontaneous discharge rate (mean 115 imp/s). In contrast to ordinary auditory units, the mean discharge rate of these neurones is not increased by infrasound or sound stimuli, but modulated by these stimuli at levels comparable to the behavioural thresholds of pigeon reported by Kreithen and Quine (1979).
The endocochlear potential (EP) in the pigeon was found to be +10 +/- 3 mV. A method for changing the EP by current injection into the scala media is described. The EP change brought about was 1.6-2.9 mV/microA and was dependent on the distance from the tip of the current electrode. Single fiber activity in the cochlear ganglion could be recorded simultaneously with the current injection. These experiments have shown that decreases in the EP reduce the sound-evoked activity of primary afferent nerves and elevate their threshold.
Brain-stem auditory evoked potentials (BAEPs) and round window compound action potentials (CAPs) in response to rarefaction and condensation clicks were recorded from anaesthetized and artificially respired caiman. The recorded wave forms were substantially different from the brain-stem and round window potentials recorded in mammals, including man. In particular, wave latencies were much longer than in mammals. Wave amplitudes increased and latencies decreased significantly and reversibly with increases in stimulus intensity and body temperature. The latencies of the first positive wave (P1) in the BAEP and the first negative wave (N1) in the CAP are correlated and co-vary with stimulus level and body temperature. BAEP P1 thus represents the response of the auditory nerve. The cochlear microphonic (CM) latency in caiman is unaffected by stimulus intensity and by cooling of the animal.
In the pigeon no influence of high doses (135 mg/kg) of furosemide on endocochlear potential and sound evoked activity in single auditory nerve fibres was found. This finding contrasts strongly to results in mammals.
Infrasound sensitive afferent fibres recorded in the pigeon cochlear ganglion were marked by intracellular injections of horseradish peroxidase (HRP). All stained fibres were found to innervate hair cells in the basilar membrane between 90 and 950 microns from its apical end. No fibres to the macula lagenae were found. Nine of the 10 completely stained fibres contacted hair cells located abneurally on the free basilar membrane, the tenth ended over the neural limbus near its abneural border. All fibres innervated between two and nine hair cells. This is in contrast to common auditory fibres in the bird that were reported to innervate only one hair cell located neurally over the neural limbus. This paper, therefore, demonstrates, for the first time, physiologically defined fibres that do not end on 'inner' hair cells.
The impulse patterns of single auditory nerve fibres in cats with normal hearing and in deafened cats were studied during electrical stimulation of the cochlea at different locations. In the case of extracochlear round-window membrane stimulation, cats with normal hearing showed lowest thresholds (32 dB re 1 microA rms) for sinusoidal stimulation in the frequency range 50-300 Hz. These thresholds were independent of the acoustically determined characteristic frequencies of the fibres. The fibres of acutely deafened cats (by Neomycin) showed no spontaneous activity and could be activated only electrically with similar current values as in normal hearing cats. The action potentials were highly synchronized with the electrical signal up to 12.8 kHz. Intracochlear electrical stimulation was performed using a human multichannel cochlear implant electrode array. The excitation thresholds of the fibres for current stimulation showed poor place dependency when using different electrodes (monopolar) in the first turn of the cochlea with a remote indifferent electrode inside the middle ear. Better localization could be obtained when using bipolar stimulation with electrode pairs (electrode distance 0.75 mm) in the scala tympani. With parallel bipolar stimulation at two different locations (distance 1.5 mm) using two independent current sources a clear interaction could be observed in the firing pattern of single fibres. The measured gain and phase relations between current signal and neuronal response allowed the calculation of a model describing the summation of current density vectors acting on an excitable nerve membrane model. On the basis of these measurements, input networks were calculated to improve the channel separation of multichannel cochlear implants.
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Neurones with low best frequency (less than 2 kHz) and sensitive to interaural phase differences were recorded in the dorsal part of the central nucleus of the cat inferior colliculus. Best frequency tone (S) and noise (N) bursts were delivered binaurally via closed field sound systems either in phase (S0, N0) at both ears or inverted at one ear (SII, NII). The responses to tone + noise bursts in the stimulus configurations S0N0, SIINII and SIIN0 and noise bursts (N0 and NII) were compared. The latter two tone + noise configurations (S0NII and SIIN0) give a binaural masking level difference (BMLD) of up to 15 dB in psychophysical experiments, i.e. an increase in noise level is necessary to mask perception of the tone. Most cells responded better to in phase stimuli (here called 0 cells). A minority of cells responded better to out of phase stimuli (here called II cells). Each cell's response was correlated with the level of acoustic stimulus (tone or masker) in the preferred configuration and not with the BMLD situation: for the 0 cells, the responses were therefore maximal for S0N0 and minimal for SIINII. For II cells, the gradation was reversed: the response to SIINII was maximal and that to S0N0 minimal. For both populations, the responses to S0NII and SIIN0 were intermediate between the S0N0 and SIINII responses. Cells that responded best to S0NII or SIIN0, i.e. cells selectively coding BMLD, were not found. This was also true for the synchronized spike rates of those cells showing phase locked responses to the stimulus frequency. Some cells appeared to be strongly suppressed by the addition of an non-preferred masker (i.e. in the configuration that resulted in less response to a noise-alone burst; e.g. NII for the 0 cells). Other cells were more suppressed by the addition of a preferred masker (N0 for the 0 cells). The difference in the number of spikes evoked by the tone + noise and the noise burst was analyzed according to signal detection theory and neuronal masked threshold determined. Some 0 cells showed lower thresholds in the configuration S0NII whereas others had higher thresholds in this configuration. This correlated with the binaural suppression effects noted above: when the noise in the preferred configuration (N0) gave more suppression, the threshold was lower for S0NII; when NII gave more suppression the threshold was higher for S0NII. Over the whole population, these effects cancelled out and the neuronal threshold was not significantly affected by the BMLD configuration.(ABSTRACT TRUNCATED AT 400 WORDS)
The motion of the conical peak of the tympanic membrane (TM) at the tip of the extra-stapedius (ES) and of the columella footplate (CFP) were measured in the pigeon using the Mössbauer technique. The dimensions of middle-ear structures were measured in some of the experimental animals. The averaged velocity response at the ES for frequencies of 0.25-2.378 kHz was that of a second order, mass and stiffness controlled, resonant system with resonant frequency of 1.2 kHz and Q3 dB of 1.2. The mean velocity amplitude at resonance was 3.7 mms-1 at 100 dB SPL, which is approximately equal to the theoretical value of 3.5 mms-1 required for maximum energy transfer from a uniform plane acoustic wavefront in air. For the frequency regions 0.125-0.25 kHz and 2.378-5.657 kHz, the mean amplitude slopes for the velocity at the ES were 2 dB oct-1 and -3 dB oct-1, respectively. Above 5.657 kHz there was considerable inter-animal variation in the ES velocity responses. The direction of motion at the ES was frequency dependent above 1 kHz. For frequencies up to 1 kHz the ratio of CFP to ES velocity was independent of frequency; the mechanical lever ratio was 2.7, which was attributed to the geometry of the middle ear. At these frequencies the total transformer ratio for the middle ear, expressing the ratio of fluid pressure at the CFP to sound pressure at the ES, was estimated to be 35 dB.
The motion of the columella footplate (CFP) was measured in the pigeon using the Mössbauer technique. At the upper frequency limit of the cochlea the measured CFP response exhibited anti-resonant phenomena. These high-frequency responses were dependent on the orientation of the radiation detector, in a way which could not be explained by the cosine effect. The dependence of the recorded phase response on the measurement axis implies an additional vibration mode, which was out of temporal phase and non-colinear with the presumed translational vibration mode. The anti-resonant phenomena were not observed when the cochlear labyrinth was extirpated, thus excluding an explanation in terms of extraneous vibrations in the experimental apparatus or of loading by the Mössbauer source. Intra-cochlear reflection is proposed as the origin of the interference mode.
The brain-stem auditory evoked potential (BAEP) was recorded in Nembutal anaesthetized cats before and after aspiration of the inferior colliculus on each side. The fast P1-P4 waves and the binaural interactions of P4 were unaffected by inferior colliculus removal. P5 and the following slow negative wave were reduced by inferior colliculus lesion. When only one inferior colliculus was ablated, this reduction was greater when the ear contralateral to the lesion side was stimulated.
This review presents recent findings on the micromechanics of the basilar membrane. Active processes are essential for basilar membrane motion. It may be that contractile proteins within the outer hair cells play an important role for this amplification. The coding of acoustic information within the auditory nerve depends on spectral analysis (place information) as well as on the time structure of the stimulus. This latter time analysis seems to play a major role.