Functional characterization of primary vestibular afferents in the frog

1. In order to more accurately identify the nature of the vestibular input to central neurons, the response properties of single semicircular canal and otolith units in the frog VIIth nerve were studied in curarized preparations. 2. An equation describing the response plane was calculated for each canal on the basis of null point measurements. These results show that the ipsilateral canal planes are orthogonal within 2-5 degrees, and the pairs of right-left synergists are essentially coplanar. A head position of 10-20 degrees maxilla nose up produces optimal horizontal canal and minimal vertical canal activation with horizontal rotation. 3. The frequency response of the horizontal canal was examined in the range 0.025-0.5 Hz. Comparatively shorter phase-lags and a 10 fold greater acceleration gain in this frequency range distinguish the frog from the mammalian species studied. 4. Otolithic responses were tonic, phasic-tonic, and phasic in nature. The preponderance of the latter two groups is stressed (94%). Tonic responses were proportional to the gravitational vector change. Phasic responses were proportional to velocity during transitions in head position and phase-led displacement (30-80%) with sinusoidal acceleration in roll and pitch. 5. Efferent vestibular neurons respond to rotation in the horizontal (usually Type III) as well as vertical planes. Responses in the vertical planes result from canal and/or otolithic input to these neurons indicating that the vestibular efferent system receives extensive multi-labyrinthine convergence.     

Dynamics and kinematics of the angular vestibulo-ocular reflex in monkey: effects of canal plugging

Dynamics and kinematics of the angular vestibulo-ocular reflex in monkey: effects of canal plugging. J. Neurophysiol. 80: 3077-3099, 1998. Horizontal and roll components of the angular vestibulo-ocular reflex (aVOR) were elicited by sinusoidal rotation at frequencies from 0.2 Hz (60 degrees/s) to 4.0 Hz ( approximately 6 degrees/s) in cynomolgus monkeys. Animals had both lateral canals plugged (VC, vertical canals intact), both lateral canals and one pair of the vertical canals plugged (RALP, right anterior and left posterior canals intact; LARP, left anterior and right posterior canal intact), or all six semicircular canal plugged (NC, no canals). In normal animals, horizontal and roll eye velocity was in phase with head velocity and peak horizontal and roll gains were approximately 0.8 and 0.6 in upright and 90 degrees pitch, respectively. NC animals had small aVOR gains at 0.2 Hz, and the temporal phases were shifted approximately 90 degrees toward acceleration. As the frequency increased to 4 Hz, aVOR temporal gains and phases tended to normalize. Findings were similar for the LARP, RALP, and VC animals when they were rotated in the planes of the plugged canals. That is, they tended to normalize at higher frequencies. A model was developed incorporating the geometric organization of the canals and first order canal-endolymph dynamics. Canal plugging was modeled as an alteration in the low frequency 3-db roll-off and corresponding dominant time constant. The shift in the low-frequency 3-dB roll-off was seen in the temporal responses as a phase lead of the aVOR toward acceleration at higher frequencies. The phase shifted toward stimulus velocity as the frequency increased toward 4.0 Hz. By incorporating a dynamic model of the canals into the three-dimensional canal system, the spatial responses were predicted at all frequencies. Animals were also stimulated with steps of velocity in planes parallel to the plugged lateral canals. This induced a response with a short time constant and low peak velocity in each monkey. Gains were normalized for step rotation with respect to time constant as (steady state eye velocity)/(stimulus acceleration x time constant). Using this procedure, the gains were the same in canal plugged as in normal animals and corresponded to gains obtained in the frequency analysis. The study suggests that canal plugging does not block the afferent response to rotation, it merely shifts the dynamic response to higher frequencies.     

Rostral fastigial nucleus activity in the alert monkey during three-dimensional passive head movements

The fastigial nucleus (FN) receives vestibular information predominantly from Purkinje cells of the vermis. FN in the monkey can be divided in a rostral part, related to spinal mechanisms, and a caudal part with oculomotor functions. To understand the role of FN during movements in space, single-unit activity in alert monkeys was recorded during passive three-dimensional head movements from rostral FN. Seated monkeys were rotated sinusoidally around a horizontal earth-fixed axis (vertical stimulation) at different orientations 15 degrees apart (including roll, pitch, vertical canal plane and intermediate planes). In addition, sinusoidal rotations around an earth-vertical axis (yaw stimulus) included different roll and pitch positions (+/-10 degrees, +/-20 degrees). The latter positions were also used for static stimulation. One hundred fifty-eight neurons in two monkeys were modulated during the sinusoidal vertical search stimulation. The vast majority showed a uniform response pattern: a maximum at a specific head orientation (response vector orientation) and a null response 90 degrees apart. Detailed analysis was obtained from 111 neurons. On the basis of their phase relation during dynamic stimulation and their response to static tilt, these neurons were classified as vertical semicircular canal related (n = 79, 71.2%) or otolith related (n = 25; 22.5%). Only seven neurons did not follow the usual response pattern and were classified as complex neurons. For the vertical canal-related neurons (n = 79) all eight major response vector orientations (ipsilateral or contralateral anterior canal, posterior canal, roll, and nose-down and nose-up pitch) were found in Fn on one side. Neurons with ipsilateral orientations were more numerous and on average more sensitive than those with contralateral orientations. Twenty-eight percent of the vertical canal-related neurons also responded to horizontal canal stimulation. None of the vertical canal-related neurons responded to static tilt. Otolith-related neurons (n = 25) had a phase relation close to head position and were considerably less numerous than canal-related neurons. Except for pitch, all other response vector orientations were found. Seventy percent of these neurons responding during dynamic stimulation also responded during static tilt. The sensitivity during dynamic stimulation was always higher than during static stimulation. Sixty-one percent of the otolith-related neurons responded also to horizontal canal stimulation. These results show that in FN, robust vestibular signals are abundant. Canal-related responses are much more common than otolith-related responses. Although for many canal neurons the responses can be related to single canal planes, convergence between vertical canals but also with horizontal canals is common.     

Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats . I. Behavioral results

We imaged the horizontal semicircular canal (HSCC) crista and cupula of toadfish, Opsanus tau, by using a) confocal light microscopy of isolated vital HSCC; b) serial sections of fixed, trichrome-stained HSCC; and c) scanning electron microscopy of fixed HSCCs. HSCC were dissections which included an ampulla and an attached canal tube (long and slender canal portion), and, in some cases, a small portion of the utricular wall. Cupulae were seen as multipartite mucus connective tissue shells rising from the crista and extending toward the ampullary roof. They were composed of several refractile bands traversing the cupulae perpendicular to longitudinal fibers extending from the cupular base to its apex. Alcian green-stained cupulae showed an asymmetric alcianphilic, dark, X-shaped structure, indicating that the pillar is rich in mucin and carbohydrate, an interpretation supported by images of trichrome-stained sections. The cupular antrum is devoid of prominent refractile fibers. No tubes or channels were observed in the cupula or antrum of vital preparations. Cupular shell fibers cover the surface of the crista, are roughly parallel, and are associated with a translucent material having a refractive index greater than the surrounding endolymph. Stereocilia were thin, 100-microm-long structures, with little longitudinal curvature, which end with no end bulb. No strands extend from stereocilia to the roof or other portions of the cupular antrum. Gross movements of stereocilia were not seen in mechanically quiescent preparations. Within the cupular antrum, stereocilia were parallel to connective tissue fibers, all embedded in an isotropic gel. This fiber-reinforced gel and cupular matrix are sensitive to N-acetlyneuraminidase and beta-N-acetyl glucosaminidase, and minimally sensitive to beta-N-acetyl hexosaminidase. Connective tissue fibers may serve to stiffen the gel, whose matrix would restrict lateral motion of embedded fibers and stereocilia thereby providing mechanical support for stereocilia.     

Responses of Purkinje cells of cerebellar vermis to sinusoidal rotation of neck

1. The response of Purkinje (P) cells located in the vermal cortex of the cerebellar anterior lobe to sinusoidal rotation of the neck was investigated in precollicular decerebrate cats. The head of the animal was fixed in a sterotaxic frame while the spinous process of the second cervical vertebra was held by a clamp rigidly fixed to the tilting table. It was then possible to elicit a selective neck input by rotating the neck and the body simultaneously along the longitudinal axis of the animal while maintaining the head in horizontal position. 2. Among the 95 P-cells tested for neck stimulation, 35 units showed a mossy fiber (MF) or a climbing fiber (CF) response to sinusoidal rotation of the axis vertebra at the frequency of 0.026 Hz and at the peak amplitude of displacement of 5--10 degrees. The response consisted in a periodic modulation of the discharge frequency during sinusoidal rotation of the neck. Most of these units were excited during side-down rotation of the neck, but were inhibited during side-up rotation. 3. The threshold amplitude of neck rotation responsible for the MF-induced responses varied in different units from 1 to 3 degrees at the frequency of 0.026 Hz. The sensitivity of the units, expressed in percentage change of the average firing rate per degree of displacement, either did not change or very slightly decreased as a result of increasing amplitude of stimulation from 1--3 degrees to 10--15 degrees at the frequency of 0.026 Hz or by increasing frequency of neck rotation from 0.015 to 0.15 Hz at the amplitude of neck displacement of 5--10 degrees. 4. Changes in amplitude or frequency of stimulation at the parameters reported above did not greatly modify the phase of the unit responses relative to the side-down position of the neck. These findings indicate that the MF and CF responses of P-cells to sinusoidal rotation of the neck depended on changes in neck position and not on changes in velocity of neck rotation. 5. The observation that the majority of responding P-cells located in the vermal cortex of the cerebellar anterior lobe increased their firing rate during side-down rotation of the neck is discussed in relation to the results of stimulation and lesion experiments, indicating that postural changes can be elicited either during asymmetric stimulation of neck receptors or by unilateral interruption of the neck afferents.     

Semicircular canal contributions to the three-dimensional vestibuloocular reflex: a model-based approach

1. We studied the contribution of the individual semicircular canals to the generation of horizontal and torsional eye movements in cynomolgus monkeys. Eye movements were elicited by sinusoidal rotation about a vertical (gravitational) axis at 0.2 Hz with the animals tilted in various attitudes of static forward or backward pitch. The gains of the horizontal and torsional components of the vestibuloocular reflex (VOR) were measured for each tilt position. The gains as a function of tilt position were fit with sinusoidal functions, and spatial gains and phases were determined. After control responses were recorded, the semicircular canals were plugged, animals were allowed to adapt, and the test procedure was repeated. Animals were prepared with only the anterior and posterior canals intact [vertical canal (VC) animals], with only the lateral canals intact [lateral canal (LC) animal], and with only one anterior and the contralateral posterior canals intact [right anterior and left posterior canal (RALP) animals; left anterior and right posterior canal (LARP) animals]. 2. In normal animals, the gain of the horizontal (yaw axis) velocity of the compensatory eye movements decreased as they were pitched forward or backward, and a torsional velocity appeared, reversing phase at the peak of the horizontal gain. After the anterior and posterior canals were plugged (LC animal), the horizontal component was reduced when the animal was tilted backward; the gain was zero with about -60 degrees of backward tilt. The spatial phase of the torsional component had the same characteristics. This is consistent with the fact that both responses were produced by the lateral canals, which from our results are tilted between 28 and 39 degrees above the horizontal stereotaxic plane. 3. After both lateral canals were plugged (VC animals), horizontal velocity was reduced in the upright position but increased as the animals were pitched backward relative to the axis of rotation. Torsional velocities, which were zero in the upright position in the normal animal, were now 180 degrees out of phase with the horizontal velocity. The peak values of the horizontal and torsional components were significantly shifted from the normal data and were closely aligned with each other, reaching peak values at approximately -56 degrees pitched back (-53 degrees horizontal, -58 degrees torsional). The same was true for the LARP and RALP animals; the peak values were at -59 degrees pitched back (-55 degrees horizontal, -62 degrees torsional). Likewise, in the LC animal the peak yaw and roll gains occurred at about the same angle of forward tilt, 35 degrees (30 degrees horizontal, 39 degrees torsional). Thus, in each case, the canal plugging had transformed the VOR from a compensatory to a direction-fixed response with regard to the head. Therefore there was no adaptation of the response planes of the individual canals after plugging. 4. The data were compared with eye velocity predictions of a model based on the geometric organization of the canals and their relation to a head coordinate frame. The model used the normal to the canal planes to form a nonorthogonal coordinate basis for representing eye velocity. An analysis of variance was used to define the goodness of fit of model predictions to the data. Model predictions and experimental data agreed closely for both normal animals and for the animals with canal lesions. Moreover, if horizontal and roll components from the LC and VC animals were combined, the summation overlay the response of the normal monkeys and the predictions of the model. In addition, a combination of the RALP and LARP animals predicted the response of the lateral-canal-plugged (VC) animals. 5. When operated animals were tested in light, the gains, peak values, and spatial phases of horizontal and roll eye velocity returned to the preoperative values, regardless of the type of surgery performed. This indicates that vision compensated for the lack o     

Effects of flicker adaptation and temporal gain control on the flicker ERG

The flicker electroretinogram (ERG) to stimuli varying in temporal frequency and modulation depth was recorded to investigate retinal gain control. With increasing modulation of a sinusoidal flickering stimulus, the flicker ERG shows an amplitude compression and a phase retardation (of the fundamental component) at 16 Hz, an amplitude expansion and a phase advance around 40-48 Hz, and an approximately linear response at 72 Hz. With sum-of-two-sinusoids stimuli, the second stimulus enhances the fundamental response to a 40 or 48 Hz test stimulus at low modulations, and reduces the variation in phase with modulation. This interaction depends primarily on the amplitude of the response to the second stimulus, but not its frequency. With temporally alternating stimuli, a similar but smaller interaction effect is measured. The results suggest that there is an active nonlinear gain control mechanism in the outer retina and this gain control works by adjusting the phase delay of the retinal response. The phase control mechanism is set by the amplitude of the outer retinal response integrated over time.     

Enhanced cochlear responses after sound exposure

Alternating potentials produced in Hensen's cells of Mongolian gerbils by sinusoidal stimuli were enhanced or depressed after exposure to broad-band sound of moderately high intensity, depending on exposure- and stimulus intensities. Since Hensen's cell responses have been shown to be identical in phase and directly proportional in magnitude to outer hair cell (OHC) responses (Oesterle, E.C., Dallos, P., 1989, J. Acoust. Soc. Am. 86 (3), 1013-1032.; Zwislocki, J.J., Slepecky, N.B., Cefaratti, L., Smith, R.L., 1992, Hear. Res. 57, 175-194), it was assumed that these changes were reflections of changes in OHC receptor potentials, which were of main interest. The indirect method of intracellularly recording the Hensen's cell potentials rather than OHC potentials was used to minimize damage to the organ of Corti and reduce technical difficulties associated with repeated recordings from OHCs. Continuous magnitude and phase transfer functions (TFs) were obtained before and after the exposure over a range of sound pressure levels (SPLs) extending from 40-90 dB by using frequency sweeps ranging from 0.125-18 kHz. Cochlear microphonic (CM) TFs were also acquired over the same frequency and intensity ranges for monitoring purposes. The exposure stimuli were set at 80, 86, 90 or 100 dB SPL for periods ranging from 10-40 min. When response enhancement occurred, it was most clearly seen in the peak of the transfer function determined at 90 dB SPL. Enhancement ranged from approximately 12-230% of the original peak. In contrast, control Hensen's cell recordings obtained over periods of up to 130 min revealed great response stability. In all reliable recordings, response enhancement was associated with a phase lead or no phase change. The strongest exposure stimuli tended to produce sensitivity loss accompanied by phase lag at the lower SPLs, in agreement with previous work in this laboratory (Zhang and Zwislocki, 1995). In some preparations, both sensitivity loss at lower SPLs and enhancement at higher SPLs occurred simultaneously, suggesting involvement of two different mechanisms.     

Kinematic principles of primate rotational vestibulo-ocular reflex. II. Gravity-dependent modulation of primary eye position

The kinematic constraints of three-dimensional eye positions were investigated in rhesus monkeys during passive head and body rotations relative to gravity. We studied fast and slow phase components of the vestibulo-ocular reflex (VOR) elicited by constant-velocity yaw rotations and sinusoidal oscillations about an earth-horizontal axis. We found that the spatial orientation of both fast and slow phase eye positions could be described locally by a planar surface with torsional variation of <2.0 +/- 0.4 degrees (displacement planes) that systematically rotated and/or shifted relative to Listing's plane. In supine/prone positions, displacement planes pitched forward/backward; in left/right ear-down positions, displacement planes were parallel shifted along the positive/negative torsional axis. Dynamically changing primary eye positions were computed from displacement planes. Torsional and vertical components of primary eye position modulated as a sinusoidal function of head orientation in space. The torsional component was maximal in ear-down positions and approximately zero in supine/prone orientations. The opposite was observed for the vertical component. Modulation of the horizontal component of primary eye position exhibited a more complex dependence. In contrast to the torsional component, which was relatively independent of rotational speed, modulation of the vertical and horizontal components of primary position depended strongly on the speed of head rotation (i.e., on the frequency of oscillation of the gravity vector component): the faster the head rotated relative to gravity, the larger was the modulation. Corresponding results were obtained when a model based on a sinusoidal dependence of instantaneous displacement planes (and primary eye position) on head orientation relative to gravity was fitted to VOR fast phase positions. When VOR fast phase positions were expressed relative to primary eye position estimated from the model fits, they were confined approximately to a single plane with a small torsional standard deviation ( approximately 1.4-2.6 degrees). This reduced torsional variation was in contrast to the large torsional spread (well >10-15 degrees ) of fast phase positions when expressed relative to Listing's plane. We conclude that primary eye position depends dynamically on head orientation relative to space rather than being fixed to the head. It defines a gravity-dependent coordinate system relative to which the torsional variability of eye positions is minimized even when the head is moved passively and vestibulo-ocular reflexes are evoked. In this general sense, Listing's law is preserved with respect to an otolith-controlled reference system that is defined dynamically by gravity.     

The response of primary horizontal semicircular canal neurons in the rat and guinea pig to angular acceleration

In rats and guinea pigs, primary afferent neurons from the horizontal semicircular canal were divided into two categories, regular and irregular, on the basis of the regularity of their resting activity. Regular neurons tend to have higher average resting rates than irregular neurons and in response to a constant angular acceleration stimulus of 16.7 deg/s2 regular neurons tended to have lower sensitivity and longer time constants than irregular cells. Some irregular neurons are more sensitive to incremental accelerations than to decremental accelerations of the same magnitude, whereas regular neurons tend to show symmetrical sensitivity. In response to sinusoidal angular acceleration stimuli (fixed frequencies) in the range 0.01-1.5 Hz, cells which fired regularly at rest tended to have smaller gain and longer phase lag re acceleration at most frequencies than irregular cells. Transfer functions were obtained for averaged data for regular and irregular neurons separately in both species. In both species there is evidence of systematic variation between neurons within each category, and this systematic variation is obscured by averaging across neurons.     

Clinical evaluation of a prototype motion artifact resistant pulse oximeter in the recovery room

Isolated posterior semicircular canals (psc) of bull frogs were used for a model of positional vertigo. Induced ampullary nerve action potentials were recorded. When the cupula was removed and the saccular otoconia were dropped onto the cilia, excitatory, and inhibitory potentials were evoked by changing the psc positions into canal-down and canal-up, respectively. When the otoconia were allowed to stay on the cupular surface, canal-down and canal-up positions also evoked excitatory and inhibitory responses, respectively. When the otoconia were inserted in the canal and were allowed to move, changing the psc positions likewise evoked responses. However, when one end of the canal was closed, these responses disappeared, indicating the efficacy of canal plugging.     

Ear canal reflectance in the presence of spontaneous otoacoustic emissions. I. Limit-cycle oscillator model

Allen et al. [Abstract in Eighteenth Midwinter Research Meeting of the Association for Research in Otolaryngology, Des Moines, IA (1995)] have found that the ear canal reflectance passes through a minimum around the frequency of a spontaneous otoacoustic emission (SOAE). They considered this result to constitute evidence against active nonlinear cochlear function as the basis for SOAEs. In order to investigate theoretically the expected behavior of ear canal reflectance in the neighborhood of a SOAE associated with an active-nonlinear cochlea, we use a simplified model in which the ear drum end of the ear canal is effectively terminated by a nonlinear-active element. Under the influence of a sinusoidal driver at the entrance of the ear canal, this element will, to a good approximation, either (1) oscillate at both the frequency of the driver (at which the reflectance is determined) and the SOAE (at a suppressed level, corresponding to nonentrainment), or (2) be entrained and only oscillate at the driving frequency. The magnitude of the nonlinear ear canal reflectance is found to exceed unity only at sufficiently low stimulus levels, and occurs under conditions of entrainment and nonentrainment of the spontaneous emission. Otherwise, the reflectance is less than unity and, as a function of frequency, has a minimum around the SOAE frequency.     

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. I. Linear acceleration responses during off-vertical axis rotation

1. The dynamic properties of otolith-ocular reflexes elicited by sinusoidal linear acceleration along the three cardinal head axes were studied during off-vertical axis rotations in rhesus monkeys. As the head rotates in space at constant velocity about an off-vertical axis, otolith-ocular reflexes are elicited in response to the sinusoidally varying linear acceleration (gravity) components along the interaural, nasooccipital, or vertical head axis. Because the frequency of these sinusoidal stimuli is proportional to the velocity of rotation, rotation at low and moderately fast speeds allows the study of the mid-and low-frequency dynamics of these otolith-ocular reflexes. 2. Animals were rotated in complete darkness in the yaw, pitch, and roll planes at velocities ranging between 7.4 and 184 degrees/s. Accordingly, otolith-ocular reflexes (manifested as sinusoidal modulations in eye position and/or slow-phase eye velocity) were quantitatively studied for stimulus frequencies ranging between 0.02 and 0.51 Hz. During yaw and roll rotation, torsional, vertical, and horizontal slow-phase eye velocity was sinusoidally modulated as a function of head position. The amplitudes of these responses were symmetric for rotations in opposite directions. In contrast, mainly vertical slow-phase eye velocity was modulated during pitch rotation. This modulation was asymmetric for rotations in opposite direction. 3. Each of these response components in a given rotation plane could be associated with an otolith-ocular response vector whose sensitivity, temporal phase, and spatial orientation were estimated on the basis of the amplitude and phase of sinusoidal modulations during both directions of rotation. Based on this analysis, which was performed either for slow-phase eye velocity alone or for total eye excursion (including both slow and fast eye movements), two distinct response patterns were observed: 1) response vectors with pronounced dynamics and spatial/temporal properties that could be characterized as the low-frequency range of "translational" otolith-ocular reflexes; and 2) response vectors associated with an eye position modulation in phase with head position ("tilt" otolith-ocular reflexes). 4. The responses associated with two otolith-ocular vectors with pronounced dynamics consisted of horizontal eye movements evoked as a function of gravity along the interaural axis and vertical eye movements elicited as a function of gravity along the vertical head axis. Both responses were characterized by a slow-phase eye velocity sensitivity that increased three- to five-fold and large phase changes of approximately 100-180 degrees between 0.02 and 0.51 Hz. These dynamic properties could suggest nontraditional temporal processing in utriculoocular and sacculoocular pathways, possibly involving spatiotemporal otolith-ocular interactions. 5. The two otolith-ocular vectors associated with eye position responses in phase with head position (tilt otolith-ocular reflexes) consisted of torsional eye movements in response to gravity along the interaural axis, and vertical eye movements in response to gravity along the nasooccipital head axis. These otolith-ocular responses did not result from an otolithic effect on slow eye movements alone. Particularly at high frequencies (i.e., high speed rotations), saccades were responsible for most of the modulation of torsional and vertical eye position, which was relatively large (on average +/- 8-10 degrees/g) and remained independent of frequency. Such reflex dynamics can be simulated by a direct coupling of primary otolith afferent inputs to the oculomotor plant. (ABSTRACT TRUNCATED)     

Diotic and dichotic detection using multiplied-noise maskers

Detection thresholds were measured with a multiplied-noise masker that was in phase in both ears and a sinusoidal signal which was either in phase or out of phase (NoSo and NoS pi conditions). The masker was generated by multiplying a low-pass noise with a sinusoidal carrier. The signal was a sinusoid with the same frequency as the carrier and a constant phase offset, theta, with respect to the carrier. By adjusting the phase offset, the stimulus properties were varied in such a way that only interaural time delays (theta = pi/2) or interaural intensity differences (theta = 0) were present within the NoS pi stimulus. Thresholds were measured at a center frequency of 4 kHz as a function of bandwidth for theta = pi/2 and for theta = 0. In a second experiment thresholds were measured for a bandwidth of 25 Hz as a function of the center frequency. The results show that narrow-band BMLDs at 4 kHz can amount to 30 dB for the theta = 0 condition. For this condition, narrow-band BMLDs are also reasonably constant across frequency, in contrast to results obtained with standard Gaussian-noise maskers. For theta = pi/2, BMLDs are restricted to the frequency region below 2 kHz provided that the masker is narrow band, but BMLDs of up to 15 dB are found at 4 kHz if the masker is 50 Hz or wider. The frequency dependence of the binaural thresholds seems to be best explained by assuming that the stimulus waveforms are compressed before binaural interaction.     

The pulsatile characteristics of hypothalamo-pituitary-adrenal activity in female Lewis and Fischer 344 rats and its relationship to differential stress responses

The dynamic patterns of basal and stimulated hypothalamo-pituitary-adrenal (HPA) activity of freely moving female Lewis and Fischer 344 rats were compared using an automated blood-sampling system. Both strains showed pulsatile corticosterone release throughout the 24 h cycle. Lewis rats showed clear circadian variation in both pulse frequency (8.4 +/- 0.4 pulses between 1700-2300 h vs. 5.3 +/- 0.8 pulses between 0500-1100 h; P < 0.05) and height (198 +/- 27 ng/ml between 1700-2300 h vs. 107 +/- 14 ng/ml between 0500-1100 h; P < 0.05). Fischer rats exhibited pulses of similar frequency and height to those in Lewis rats during the evening, but showed no circadian variation, resulting in higher mean daily corticosterone concentrations. Although both strains showed behavioral and HPA responses to white noise stress (10 min; 114 dB), Fischer rats showed much greater increases in total activity, grooming, and rearings, and two important differences in the corticosterone responses were observed. First, in Lewis rats a clear relationship existed between basal and stimulated HPA activities, in that a significant response was seen only when the stress coincided with the rising (secretory active) phase of a basal pulse. Noise stress coinciding with a falling (nonsecretory) phase elicited no significant response. In contrast, Fischer rats showed similar responses regardless of the underlying pulse phase. Second, after the peak response at 20 min (Lewis, 237 +/- 67 ng/ml; Fischer, 390 +/- 57 ng/ml), corticosterone levels fell rapidly in Lewis rats, but remained maximally elevated for 20 min in Fischer rats, resulting in a significantly greater integrated response. The corticosterone response to i.v. CRF was unaffected by pulse phase in both strains, suggesting that a suprapituitary mechanism mediates the phase-dependent response to stress in the Lewis strain. CRF-induced corticosterone levels rose more rapidly in Fischer rats, peaking at 10 min (473 +/- 95 ng/ml) compared with 30 min (390 +/- 75 ng/ml) in Lewis rats, suggesting greater pituitary sensitivity in this strain. Thus, differences in both central and pituitary control of the HPA axis contribute to the strain difference in stress responsiveness between female Lewis and Fischer rats.     

Reducing maternal smoking and relapse: long-term evaluation of a pediatric intervention

Simultaneous recordings of action potentials (APs) of multiple single motor units (MUs) were obtained in brachialis and biceps (caput breve) muscles during sinusoidally modulated isometric contractions of elbow flexor muscles and during sinusoidal flexion/extension movements in the elbow against a preload in the extension direction. The results show that MUs typically fire in one short burst for each sinusoidal cycle. The mean phase lead of the bursts of APs relative to a sinusoidally modulated isometric torque in the elbow joint or relative to sinusoidal movements in the elbow increases gradually with frequency. The increase of the mean phase lead during isometric contractions was very similar for all MUs and could be explained well by modeling the force production of MUs with a second-order linear low-pass system. For sinusoidal flexion/extension movements each MU reveals a specific, reproducible phase lead as a function of frequency. However, there is a large variability in phase behavior between MUs. Also, the modulation of the firing rate for sinusoidal isometric contractions versus sinusoidal movements appeared to be different for various MUs. In simultaneous recordings some MUs clearly revealed a larger firing rate in each burst for movements relative to isometric contractions, whereas other MUs revealed a smaller firing rate. This suggests that some MUs are preferentially activated during movements whereas others are preferably activated during isometric contractions. The results demonstrate task-dependent changes in the relative activation of MUs within a single muscle for sinusoidal isometric contractions and movements.     

Role of WUSCHEL in regulating stem cell fate in the Arabidopsis shoot meristem

This paper reports on directional response properties of saccular afferents of the sleeper goby, Dormitator latifrons, to 100-Hz acoustic particle motions with a focus on testing the hypothesis that the response directionality of a fish's auditory afferents derives from the morphological polarity of sensory hair cells in the otolithic organs. Spontaneous rates (SR) and best sensitivities (BS) of saccular afferents ranged from 0 to 162 spikes/sec and from 0.2-to 100-nm RMS displacement. SR did not vary with BS. Most saccular afferents were phase-locked to sinusoidal stimulation and had sustained temporal response patterns with some adaptation. All saccular afferents were directionally sensitive to the stimulus, and the sharpness of directional response curves was determined by a directionality index (DI). The DI ranged from 0.64 to 1.50 (mean = 1.02, SE = 0.02, n = 100) and gradually decreased with stimulus level throughout afferents' response dynamic range. Many afferents had approximately symmetric directional response curves relative to their best response axes (BRA). BRA of most afferents remained constant with stimulus level. The BRA distribution had a peak along an axis that correlates closely with the morphological polarity of saccular hair cells. Therefore, our results strongly support the hypothesis.     

Futures market in organ procurement

Five-minute ultrasonic exposure of 0.4 Wt/cm2 intensity and 880 kHz frequency at acoustic contact through isotonic NaCl solution in the permanent mode (10-15 sessions) in combination with exposure to sinusoidal alternating 50-period magnetic field for up to 20 min had a positive stable therapeutic effect in patients with initial and immature senile cataracts, decelerating the processes of maturing. A course of treatment consisted of regular annual therapy according to the above protocol. The best results were attained in the group treated at the sanatorium and administered a course of complex spa therapy; this is one more confirmation that senile cataract is a dysfunction of the ageing organism suffering from many diseases requiring total-systems treatment in addition to the treatment for cataract.     

结晶器液压振动台振动状态检测与分析

结晶器振动在连铸生产中具有重要的作用,液压振动是近年来被开发并逐渐推广应用的结晶器振动方式.基于板坯连铸结晶器液压振动装置,通过检测结晶器液压振动装置的位移等参数,对振动系统的振动状态的检测与评价进行试验研究.分析了不同振动参数下两侧液压缸位移偏差、相位差随振动参数的变化规律.结果表明,结晶器液压振动装置具有较高的振动精度.为液压振动条件下结晶器振动状态的检测与评价提供了一种方法.     

Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human live microsomes and nine recombinant human cytochromes P450

Studies using human liver microsomes and nine recombinant human cytochrome P450 (CYP) isoforms (CYP1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4) were performed to identify the CYP isoform(s) involved in the major metabolic pathway (3-hydroxylation) of quinine in humans. Eadie-Hofstee plots for the formation of 3-hydroxyquinine exhibited apparently monophasic behavior for all of the 10 different microsomal samples studies. There was interindividual variability in the kinetic parameters, as follows: 1.8-, 3.2- and 3.5-fold for K(m) Vmax and Vmax/K(m), respectively. The mean +/- S.D. values for K(m), Vmax and Vmax/K(m) were 106.1 +/- 19.3 microM, 1.33 +/- 0.48 nmol/mg protein/min and 12.8 +/- 5.1 microliters/mg protein/min, respectively. With 10 different human liver microsomes, the relationships between the 3-hydroxylation of quinine and the metabolic activities for substrates of the respective CYP isoforms were evaluated. The 3-hydroxylation of quinine showed an excellent correlation (r = 0.986, P < .001) with 6 beta-hydroxylation of testosterone, a marker substrate for CYP3A4. A significant correlation (r = 0.768, P < .01) between the quinine 3-hydroxylase and S-mephenytoin 4'-hydroxylase activities was also observed. However, no significant correlation existed between the 3-hydroxylation of quinine and the oxidative activities for substrates for CYP1A2 (phenacetin), 2C9 (diclofenac), 2D6 (desipramine) and 2E1 (chlorzoxazone). Ketoconazole and troleandomycin (inhibitors of CYP3A4) inhibited the 3-hydroxylation of quinine by human liver microsomes with respective mean IC50 values of 0.026 microM and 28.9 microM. Anti-CYP3A antibodies strongly inhibited quinine 3-hydroxylation, whereas weak inhibition was observed in the presence of S-mephenytoin or anti-CYP2C antibodies. Among the nine recombinant human CYP isoforms, CYP3A4 exhibited the highest catalytic activity with respect to the 3-hydroxylation of quinine, compared with the minor activity of CYP2C19 and little discernible or no effect of other CYP isoforms. Collectively, these data suggest that the 3-hydroxylation of quinine is mediated mainly by CYP3A4 and to a minor extent by CYP2C19. Other CYP isoforms used herein appear to be of negligible importance in this major pathway of quinine in humans.