Postlesional vestibular reorganization improves the gain but impairs the spatial tuning of the maculo-ocular reflex in frogs

The ramus anterior (RA) of N.VIII was sectioned unilaterally. Two months later we analyzed in vivo responses of the ipsi- and of the contralesional abducens nerve during horizontal and vertical linear acceleration in darkness. The contralesional abducens nerve had become responsive again to linear acceleration either because of a synaptic reorganization in the vestibular nuclei on the operated side and/or because of a reinnervation of the utricular macula by regenerating afferent nerve fibers. Significant differences in the onset latencies and in the acceleration sensitivities allowed a separation of RA frogs in a group without and in a group with functional utricular reinnervation. Most important, the vector orientation for maximal abducens nerve responses was clearly altered: postlesional synaptic reorganization resulted in the emergence of abducens nerve responses to vertical linear acceleration, a response component that was barely detectable in RA frogs with utricular reinnervation and that was absent in controls. The ipsilesional abducens nerve, however, exhibited unaltered responses in either group of RA frogs. The altered spatial tuning properties of contralesional abducens nerve responses are a direct consequence of the postlesional expansion of signals from intact afferent nerve and excitatory commissural fibers onto disfacilitated 2nd-order vestibular neurons on the operated side. These results corroborate the notion that postlesional vestibular reorganization activates a basic neural reaction pattern with more beneficial results at the cellular than at the network level. However, given that the underlying mechanism is activity-related, rehabilitative training after vestibular nerve lesion can be expected to shape the ongoing reorganization.     

Parabrachial nucleus neuronal responses to off-vertical axis rotation in macaques

The caudal aspect of the parabrachial nucleus (PBN) contains neurons responsive to whole body, periodic rotational stimulation in alert monkeys (Balaban et al. in J Neurophysiol 88:3175–3193, 2002). This study characterizes the angular and linear motion-sensitive response properties of PBN unit responses during off-vertical axis rotation (OVAR) and position trapezoid stimulation. The OVAR responses displayed a constant firing component which varied from the firing rate at rest. Nearly two-thirds of the units also modulated their discharges with respect to head orientation (re: gravity) during constant velocity OVAR stimulation. The modulated response magnitudes were equal during ipsilateral and contralateral OVARs, indicative of a one-dimensional accelerometer. These response orientations during OVAR divided the units into three spatially tuned populations, with peak modulation responses centered in the ipsilateral ear down, contralateral anterior semicircular canal down, and occiput down orientations. Because the orientation of the OVAR modulation response was opposite in polarity to the orientation of the static tilt component of responses to position trapezoids for the majority of units, the linear acceleration responses were divided into colinear dynamic linear and static tilt components. The orientations of these unit responses formed two distinct population response axes: (1) units with an interaural linear response axis and (2) units with an ipsilateral anterior semicircular canal-contralateral posterior semicircular canal plane linear response axis. The angular rotation sensitivity of these units is in a head-vertical plane that either contains the linear acceleration response axis or is perpendicular to the linear acceleration axis. Hence, these units behave like head-based (‘strapdown’) inertial guidance sensors. Because the PBN contributes to sensory and interoceptive processing, it is suggested that vestibulo-recipient caudal PBN units may detect potentially dangerous anomalies in control of postural stability during locomotion. In particular, these signals may contribute to the range of affective and emotional responses that include panic associated with falling, malaise associated with motion sickness and mal-de-debarquement, and comorbid balance and anxiety disorders.     

The contribution of the horizontal semicircular canals to the response to off-vertical-axis rotation in the cat

Summary The response to off-vertical-axis rotation (OVAR) was measured in cats under circumstances in which the signals from the horizontal semicircular canals and otoliths were opposed. Opposition was achieved by sudden acceleration or deceleration during constant velocity OVAR. The degree of opposition was expressed as a canal/otolith ratio where a ratio of unity indicated agreement. For a canal/otolith ratio of 1, the OVAR gain (eye velocity/ stimulus velocity) was 0.73 (±0.13). The steady-state OVAR response was, however, reduced if the canals and otoliths were opposed. The reduction depended on the degree of opposition with a fall-off of 0.15 gain/(unit of canal/otolith ratio). These findings are discussed with respect to the central velocity store and the mechanism underlying the generation of the OVAR response.     

Vestibular and optokinetic eye movements evoked in the cat by rotation about a tilted axis

Summary Horizontal and vertical eye movements were recorded from cats in response to either a) off-vertical axis rotation (OVAR) at a range of velocities (5–72 deg/s) and a range of tilts (0–60 deg) or b) horizontal (with respect to the cat) optokinetic stimulation (10–80 deg/s), also around a range of tilted axes (0–60 deg). The responses to stopping either of these stimuli were also measured: post-rotatory nystagmus (PRN) following actual rotation, and optokinetic after nystagmus (OKAN) following optokinetic stimulation. The response found during OVAR was a nystagmus with a bias slow-phase velocity that was sinusoidally modulated. The bias was dependent on the tilt and reached 50% of its maximum velocity (maximum was 73±23% of the table velocity) at a tilt of 16 deg. The phase of modulation in horizontal eye velocity bore no consistent relation to the angular rotation. The amplitude of this modulation was roughly correlated with the bias with a slope of 0.13 (deg/s) modulation/(deg/s) bias velocity. There was also a low-velocity vertical bias with the slow-phases upwardly directed. The vertical bias was also modulated and the amplitude depended on the bias velocity (0.27 (deg/s) modulation/ (deg/s) bias velocity). When separated from the canal dependent response, the build up of the OVAR response had a time constant of 5.0±0.8 s. Following OVAR there was no decline in the time constant of PRN which remained at the value measured during earth-vertical axis rotation (EVAR) (6.3±2 s). The peak amplitude of PRN was reduced, dependent on the tilt, reaching only 20% of its EVAR value for a tilt of 20 deg. When a measurable PRN was found, it was accompanied by a slowly-emerging vertical component (time constant 5.4±2s) the effect of which was to vector the PRN accurately onto the earth horizontal. OKN measured about a tilted axis showed no differences in magnitude or direction from EVAR OKN even for tilts as large as 60 deg. OKAN following optokinetic stimulation around a tilted axis appeared normal in the horizontal plane (with respect to the animal) but was accompanied by a slowly emerging (time constant 4.1±2 s) vertical component, the effect of which was to vector the overall OKAN response onto the earth horizontal for tilts less than 20 deg. These results are compared with data from monkey and man and discussed in terms of the involvement of the velocity storage mechanism.     

Neural basis for eye velocity generation in the vestibular nuclei of alert monkeys during off-vertical axis rotation

Summary Activity of vestibular only (VO) and vestibular plus saccade (VPS) units was recorded in the rostral part of the medial vestibular nucleus and caudal part of the superior vestibular nucleus of alert rhesus monkeys. By estimating the null axes of recorded units (n = 79), the optimal plane of activation was approximately the mean plane of reciprocal semicircular canals, i.e., lateral canals, left anterior-right posterior (LARP) canals or right anterior-left posterior (RALP) canals. All units were excited by rotation in a direction that excited a corresponding ipsilateral semicircular canal. Thus, they all displayed a type I response. With the animal upright, there were rapid changes in firing rates of both VO and VPS units in response to steps of angular velocity about a vertical axis. The units were bidirectionally activated during vestibular nystagmus (VN), horizontal optokinetic nystagmus (OKN), optokinetic afternystagmus (OKAN) and off-vertical axis rotation (OVAR). The rising and falling time constants of the responses to rotation indicated that they were closely linked to velocity storage. There were differences between VPS and VO neurons in that activity of VO units followed the expected time course in response to a stimulus even during periods of drowsiness, when eye volocity was reduced. Firing rates of VPS units, on the other hand, were significantly reduced in the drowsy state. Lateral canal-related units had average firing rates that were linearly related to the bias or steady state level of horizontal eye velocity during OVAR over a range of ±60 deg/s. These units could be further divided into two classes according to whether they were modulated during OVAR. Non-modulated units (n = 5) were VO types and all modulated units (n = 5) were VPS types. There was no significant difference between the bias level sensitivities relative to eye velocity of the units with and without modulation (P>0.05). The modulated units had no sustained change in firing rate in response to static head tilts and their phases relative to head position varied from unit to unit. The phase did not appear to be linked to the modulation of horizontal eye velocity during OVAR. The sensitivities of unit activity to eye velocity were similar during all stimulus modalities despite the different gains of eye velocity vs stimulus velocity during VN, OKN and OVAR. Therefore, VO and VPS units are likely to carry an eye velocity signal related to velocity storage. For example, when unit sensitivities were related to head or surround velocity, sensitivity relative to OVAR was less than for VN or OKN. Firing rates of both vertical canal-related VO and VPS units (n= 19) were strongly modulated during OVAR, although they did not show changes in discharge rate during static head tilts relative to the spatial vertical up to a maximal 25 deg. In some cases the amplitude of the modulation increased with increases in head velocity and eye velocity. Average activity of vertical canal-related units was linearly related to steady state horizontal eye velocity in the ipsilateral direction during OVAR. The mean sensitivities of RALP units were not significantly different from those of LARP neurons (P>0.05). Together, their mean sensitivity during OVAR about a subject yaw axis was 0.34 (imp/s)/(deg/s) relative to horizontal eye velocity. This could be explained as a contribution of the vertical canals to horizontal eye velocity due to their orientation in the head. During OVAR to the ipsilateral side, the bias level of neuronal activity decreased and saturated. For steps of rotation about a vertical axis with the animal upright, the firing rates of RALP and LARP units were linearly related to stimulus velocity and eye velocity. Contralateral rotation excited the units reflecting the orientation of the semicircular canals relative to the yaw axis of rotation. RALP and LARP units also responded during horizontal optokinetic stimulation producing both OKN and OKAN. All the vertical canal units had dynamic characteristics closely related to velocity storage. Their response characteristics were consistent with the model that they contribute to horizontal slow phase velocity as part of a three-dimensional system based on a semicircular canal frame of reference. Otolith-related units (n= 5) in the vestibular nuclei showed no evidence of velocity storage and were modulated in accordance with head position during OVAR. Mean amplitude of the modulation of activity during OVAR at a 20 deg tilt and 60 deg/s rotational velocity was 24 imp/s. The data indicate that the vestibular nuclei contain the requisite signals to generate horizontal eye velocity during OVAR. VO and VPS units probably contribute to the bias or velocity storage component while otolith units mainly contribute to the oscillations in eye velocity by generating gravity dependent eye position changes during OVAR. In addition to the velocity storage component of horizontal eye velocity, the vertical VO neurons also have oscillations in their discharge patterns probably related to the vertical component of eye movements generated by the velocity storage integrator.     

Evaluation of the vestibulo-ocular reflex using sinusoidal off-vertical axis rotation in patients with acoustic neurinoma

The vestibulo-ocular reflex (VOR) was studied to examine the utility of off-vertical axis rotation (OVAR) in the diagnosis of acoustic neurinoma. Subjects were sinusoidally rotated with eyes open in complete darkness at frequencies of 0.4 and 0.8 Hz with a maximum angular velocity of 60°/s at either earth-vertical axis rotation (EVAR) or OVAR. Thirteen patients with acoustic neurinomas were investigated. Results showed that VOR gain during OVAR at 0.8 Hz and in a 30° nose-up position in patients with internal auditory canal tumors was significantly less than the gain measured during EVAR. The VOR gain measured from all patients (including those with tumors extending to the cerebellopontine angle) was not significantly different when the patients were subjected to EVAR and OVAR. These observations were possibly due to superior vestibular nerve dysfunction. We concluded that certain stimulating parameters—patient's nose tilted up 30°; sinusoidal OVAR at 0.8 Hz and 60°/s maximum angular head velocity—were useful for evaluating vestibular function in patients suffering from an acoustic neurinoma located within the internal auditory canal.     

Expansion of afferent vestibular signals after the section of one of the vestibular nerve branches

The anterior branch of N. VIII was sectioned in adult frogs. Two months later the brain was isolated to record in vitro responses in the vestibular nuclei and from the abducens nerves following electric stimulation of the anterior branch of N. VIII or of the posterior canal nerve. Extra- and intracellularly recorded responses from the intact and operated side were compared with responses from controls. Major changes were detected on the operated side: the amplitudes of posterior canal nerve evoked field potentials were enlarged, the number of vestibular neurons with a monosynaptic input from the posterior canal nerve had increased, and posterior canal nerve stimulation recruited stronger abducens nerve responses on the intact side than vice versa. Changes in the convergence pattern of vestibular nerve afferent inputs on the operated side strongly suggest the expansion of posterior canal-related afferent inputs onto part of those vestibular neurons that were deprived of their afferent vestibular input. As a mechanism we suggest reactive synaptogenesis between intact posterior canal afferent fibers and vestibularly deprived second-order vestibular neurons.     

Role of irregular otolith afferents in the steady-state nystagmus during off-vertical axis rotation.

1. During constant velocity off-vertical axis rotations (OVAR) in the dark a compensatory ocular nystagmus is present throughout rotation despite the lack of a maintained signal from the semicircular canals. Lesion experiments and canal plugging have attributed the steady-state ocular nystagmus during OVAR to inputs from the otolith organs and have demonstrated that it depends on an intact velocity storage mechanism. 2. To test whether irregularly discharging otolith afferents play a crucial role in the generation of the steady-state eye nystagmus during OVAR, we have used anodal (inhibitory) currents bilaterally to selectively and reversibly block irregular vestibular afferent discharge. During delivery of DC anodal currents (100 microA) bilaterally to both ears, the slow phase eye velocity of the steady-state nystagmus during OVAR was reduced or completely abolished. The disruption of the steady-state nystagmus was transient and lasted only during the period of galvanic stimulation. 3. To distinguish a possible effect of ablation of the background discharge rates of irregular vestibular afferents on the velocity storage mechanism from specific contributions of the dynamic responses from irregular otolith afferents to the circuit responsible for the generation of the steady-state nystagmus, bilateral DC anodal galvanic stimulation was applied during optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN). No change in OKN and OKAN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Timing of low frequency responses of anterior and posterior canal vestibulo-ocular neurons in alert cats

The pitch vertical vestibulo-ocular reflex (VOR) is accurate and symmetrical when tested in the normal upright posture, where otolith organ and central velocity storage signals supplement the basic VOR mediated by the semicircular canals. However, when the animal and rotation axis are together repositioned by rolling 90° to one side, head forward pitch rotations that excite the anterior semicircular canals elicit a more accurately timed VOR than do oppositely directed rotations that excite the posterior canals. This suggests that velocity storage of posterior canal signals is lost when the head is placed on its side. We recorded from 47 VOR relay neurons, second-order vestibulo-ocular neurons, of alert cats to test whether asymmetries are evident in the responses of neurons in the medial and superior vestibular nuclei during earth-horizontal axis rotations in the normal upright posture. Neurons were identified by antidromic responses to oculomotor nucleus stimulation and orthodromic responses to labyrinth stimulation, and were classified as having primarily anterior, posterior, or horizontal canal input based on response directionality. Neuronal response gains and phases were recorded during 0.5 Hz and 0.05 Hz sinusoidal oscillations in darkness. During 0.5 Hz rotations, anterior canal second-order vestibulo-ocular neurons responded approximately in phase with head velocity (mean phase re head position, ±SE, 80°±3°, n=18), as did posterior canal second-order vestibulo-ocular neurons (mean phase 81°±1°, n=25). Lowering the rotation frequency to 0.05 Hz resulted in only slight advances in response phases of individual anterior canal second-order vestibulo-ocular neurons (mean phase 86°±6°, mean advance 7°±5°, n=12). In contrast, posterior canal second-order vestibulo-ocular neurons behaved more like semicircular canal afferents, with responses markedly phase-advanced (mean advance 28°±5°, n=14) by lowering rotation frequency to 0.05 Hz (mean phase 111°±5°, n=14). In summary, low frequency responses of anterior and posterior canal second-order vestibulo-ocular neurons recorded during horizontal axis pitch correspond to the VOR they excite during vertical axis pitch. These results show that velocity storage is evident at anterior but not posterior canal second-order vestibulo-ocular neurons. We conclude that responses of posterior canal second-order vestibulo-ocular neurons are insufficient to explain the accurate low frequency VOR phase observed during backward head pitch in the upright posture, and that velocity storage or otolith signals required for VOR accuracy are carried by other neurons. Electronic Publication     

Morphophysiological study on the divergent projection of axon collaterals of medial vestibular nucleus neurons in the cat

(1) Spikes of single neurons were extracellularly recorded in the medial vestibular nucleus (MVN) in decerebrate cats and were functionally identified as secondary type I neurons by observing their responses to horizontal rotation and monosynaptic activation after stimulation of the ipsilateral vestibular nerve. Axonal projection of these neurons was examined by their antidromic responses to stimulation of the contralateral abducens nucleus, the spinal cord, and the ascending and descending MLF. (2) Almost all secondary type I vestibular neurons which sent their axon to the contralateral abducens nucleus were antidromically activated from the descending MLF at the level of the obex as well. Nearly half of these neurons sent their collateral axon to the level of C1 segment in the spinal cord and approximately one third to the ascending MLF close to the oculomotor complex. (3) The mean conduction velocity was 29 m/s for descending collateral axons and 30 m/s for ascending collateral axons. (4) Systematic tracking for antidromic microstimulation in the contralateral abducens nucleus and spinal gray matter at C2-C3 suggested that collateral axons of single type I vestibular neurons gave off local branches in the abducens nucleus and the motoneuron pool in the upper cervical gray matter. Existence of terminal branches in the neck motoneuron pool was confirmed by intraaxonal staining with horseradish peroxidase (HRP). (5) Neurons which projected to both the contralateral abducens nucleus and the spinal cord were located in a fairly localized region in the ventrolateral part of the rostral MVN. Neurons which projected to the contralateral abducens nucleus and not to the spinal cord were located in a rostrocaudally wider area in the ventrolateral MVN. Neurons projecting to the spinal cord and not to the contralateral abducens nucleus were located in the widest area in the rostrocaudal direction, covering almost the whole extent of the rostral half of the MVN.     

Principles of linear and angular vestibuloocular reflex organization in the frog.

We compared the spatial organization patterns of linear and angular vestibuloocular reflexes in frogs by recording the multiunit spike activity from cranial nerve branches innervating the lateral rectus, the inferior rectus, or the inferior obliquus eye muscles. Responses were evoked by linear horizontal and/or vertical accelerations on a sled or by angular accelerations about an earth-vertical axis on a turntable. Before each sinusoidal oscillation test in darkness, the static head position was systematically altered to determine those directions of horizontal linear acceleration and those planes of angular head oscillation that were associated with minimal response amplitudes. Inhibitory response components during angular accelerations were clearly present, whereas inhibitory response components during linear accelerations were absent. Likewise was no contribution from the vertical otolith organs (i.e., lagena and saccule) observed during vertical linear acceleration. Horizontal linear acceleration evoked responses that originated from eye muscle-specific sectors on the contralateral utricular macula. The sectors of the inferior obliquus and lateral rectus muscles on the utricle had an opening angle of 45 and 60 degrees, respectively and overlapped to a large extent in the laterorostral part of the utricle. Both sectors were coplanar with the horizontal semicircular canals. The sector of the inferior rectus muscle was narrow (opening 5 degrees), laterocaudally oriented, and slightly pitched up by 6 degrees. Angular acceleration evoked maximal responses in the inferior obliquus muscle nerve that originated from the ipsilateral horizontal and the contralateral anterior vertical canals in a ratio of 50:50. Lateral rectus excitation originated from the contralateral horizontal and anterior vertical semicircular canals in a ratio of 80:20. The excitatory responses of the inferior rectus muscle nerve originated exclusively from the contralateral posterior vertical canal. Measured data and known semicircular canal plane vectors were used to calculate the spatial orientation of maximum sensitivity vectors for the investigated eye muscle nerves in semicircular canal coordinates. Comparison of the directions of maximal sensitivity vectors of responses evoked by linear or angular accelerations in a given eye muscle nerve showed that the two vector directions were oriented about orthogonally with respect to each other. With this arrangement the linear and the angular vestibuloocular reflex can support each other dynamically whenever they are co-activated without a change in the spatial response characteristics. The mutual adaptation of angular and linear vestibuloocular reflexes as well as the differences in their organization described here for frogs may represent a basic feature common for vertebrates in general.     

Effect of trans-bullar gentamicin treatment on guinea pig angular and linear vestibulo-ocular reflexes

This study provides the first systematic examination of the effects of intratympanic gentamicin instillation on vestibulo-ocular responses of guinea pigs during both Earth-vertical yaw axis and off-vertical axis rotation. A scleral search coil was sutured to the right eye of pigmented female guinea pigs prior to trans-bullar instillation of a 0.2-ml bolus of either 20 mg/ml or 40 mg/ml of gentamicin (1) into the right middle ear (unilateral treatment groups) or (2) into both ears (bilateral treatment groups). Two weeks later, eye movement responses were tested during yaw axis sinusoidal rotation at 7 frequencies (0.02, 0.05, 0.1, 0.2, 0.5, 1 and 2 Hz, 40 deg/s peak velocity) and during off-vertical axis rotation at five constant velocities (20, 40, 60, 80 and 100 deg/s), tilted 30 deg relative to the earth-vertical axis. The main result was that unilateral trans-bullar gentamicin instillation produced almost exclusively unidirectional deficits in horizontal angular vestibulocular reflex (HVOR) responses and modulation and bias responses to off-vertical axis rotation (OVAR). The HVOR gain was reduced during rotation toward the injected ear in a dose-dependent manner for frequencies of 1 Hz and lower, but there was no effect on responses during rotation toward the intact ear. Further, the modulation and bias responses to OVAR were reduced profoundly in a dose-dependent manner during rotation toward the treated ear. It is suggested that these effects indicate selective cytotoxic and/or physiologic effects of gentamicin intoxication in the inner ear or, possibly, the vestibular nerve and central nervous system.     

Extraocular proprioceptive signals affect ocular motor activity neither directly nor parametrically in the presence of optokinetic or vestibular stimulation in the frog

Summary Direct and parametric effects of stretch receptors in the extraocular muscles on abducens nerve activity were investigated in the unanesthetized immobilized frog. Horizontal passive rotations of one eye in the physiological range (±5°) did not elicit responses in the activity of abducens nerve on either side; however, larger rotations or pull of one eye evoked long latency direction-unspecific responses simultaneously in both nerves. When the animal was stimulated vestibulary in the horizontal plane with sinusoidal or constant acceleration, abducens activity was not altered in correlation to passive eye movements in the physiological range. Similarly, the activity of either nerve evoked by simultaneous or preceding optokinetic stimulation of one eye with constant pattern velocity was not modified by passive rotation of the contralateral eye.     

Low-frequency otolith and semicircular canal interactions after canal inactivation

During sustained constant velocity and low-frequency off-vertical axis rotations (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The adaptive plasticity of these responses was investigated here after semicircular canal plugging. Inactivation of semicircular canals results in a highly compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR enhancement hypothesis, one could expect an adaptive increase of otolith-borne angular velocity signals due to combined otolith/canal inputs after inactivation of the semicircular canals. Contrary to expectations, however, the steady-state slow-phase velocity during constant velocity OVAR decreased in amplitude over time. A similar progressive decrease in VOR gain was also observed during low-frequency off-vertical axis oscillations. This response deterioration was present in animals with either lateral or vertical semicircular canals inactivated and was limited to the plane(s) of the plugged canals. The results are consistent with the idea that the low-frequency otolith signals do not simply enhance VOR responses. Rather, the nervous system appears to correlate vestibular sensory information from the otoliths and the semicircular canals to generate an integral response to head motion.     

Partial restitution of lesion-induced deficits in the horizontal vestibulo-ocular reflex performance measured from the bilateral abducens motor output in frogs

Summary The responses of the bilateral abducens nerves to small table velocity steps in the dark were measured in four groups of animals: One group was intact prior to recording (controls), one group was hemi-labyrinthectomized the day before the recordings (acute HL), the horizontal canal nerve was sectioned the day before the recordings (acute HCN) in another and the last group was hemilabyrinthectomized between 60 and 90 days prior to recording (chronic HL). In controls (N = 6) the slopes of the change in discharge rate to increasingly larger velocity steps increased maximally with about 200 imp/s per 1°/s and decreased maximally with about –60 imp/s per 1°/s. This difference is explained by low resting rates and by recruitment of spontaneously inactive vestibular afferent, central vestibular and abducens neurons. Results obtained from acute HL (N = 4) and acute HCN (N = 4) animals were practically identical. In neither case was a spontaneous nystagmic activity pattern observed. Results differed from those obtained in controls due to an asymmetric reduction in responsiveness. Comparison of the slopes of the evoked increases and decreases in discharge rates of abducens nerves to increasingly larger velocity steps with those in controls show that normal abducens responses are predominantly controlled by crossed excitation and by uncrossed inhibition. Disinhibition and disfacilitation play minor roles. In chronic HL animals (N = 6) that had posturally recovered to a similar degree, responses evoked by steps towards the intact side at larger velocity steps were slightly reduced with respect to those in acute HL or HCN animals. Responses evoked by steps towards the lesioned side differed between individuals. They were either similar to those in controls (N = 1), to those in acute animals (N = 2) or lay between these two extremes (N = 3). The improvement in response to velocity steps towards the lesioned side in 4 of 6 animals is explained by an increase in activity released by disinhibition. This inhibition in turn is controlled by horizontal canal-dependent input from the intact side. Plugging of this canal abolished all direction-specific responses in this plane in the dark, suggesting that the partial restitution of function of horizontal reflex performance depends exclusively on signals derived from receptors of this canal.Prof. Precht died on March 12, 1985     

Motor output to lateral rectus in cats during the vestibulo-ocular reflex in three-dimensional space

The motor output to the lateral rectus eye muscle was studied in decerebrate cats with electromyographic recordings and in alert cats with multi-unit and single neuron recordings from abducens nucleus. The axis of rotation that produced maximal excitation of the lateral rectus was calculated from responses to rotations in many different stimulus orientations, and was found to lie near the axis of the horizontal semicircular canals, but pitched slightly nose down from the canal axis (4.6 degrees). The results from decerebrate and alert cats were in agreement. The dynamics of lateral rectus activation were quite similar in all planes. Responses at high frequencies were in phase with rotation velocity and responses lagged toward position phase as frequency and velocity were decreased. Differences in decerebrate cat low frequency responses to rotations with and without a sinusoidal gravitational stimulus implicated an otolith input to lateral rectus.     

Dynamics of vestibular neurons during rotational motion in alert rhesus monkeys

The temporal processing in the encoding of head rotation was investigated by comparing the dynamics of vestibular nuclei neurons with those of the regularly and irregularly firing semicircular canal afferents in alert rhesus monkeys. During earth-vertical axis rotations, neurons without eye movement sensitivity differed in their response dynamics from both regularly and irregularly firing semicircular canal afferents. At high frequencies, central responses increased in sensitivity and maintained phase leads of nearly 30° relative to head velocity. These persistent high-frequency phase leads resembled those of irregularly firing (but not regularly firing) semicircular canal afferents. However, at low frequencies, central responses exhibited significantly smaller phase leads than those of irregularly firing semicircular canal afferents, and dynamics resembled more those of the regularly firing afferents. The response dynamics of central non-eye movement cells were significantly different from those of position-vestibular-pause and eye-head neurons (collectively referred to as eye movement cells). In contrast to the persistent phase leads of non-eye movement neurons, all eye movement cells modulated closely in phase with head velocity at all frequencies down to 0.05 Hz during visual suppression tasks. Vertical canal non-eye movement neurons that were insensitive to both translations and static head tilts led head velocity by approximately 5–30° during high-frequency earth-horizontal axis rotations. Unlike the earth-vertical axis responses that led head velocity at low frequencies by as much as 20–40°, vertical canal neurons only slightly led or even lagged behind head velocity during low-frequency earth-horizontal axis rotations. Posterior canal central non-eye movement cells lagged behind head velocity significantly more than anterior canal neurons. These frequency dependencies of central vestibular neurons in comparison with those of the afferents suggest that both low- and high-pass filtering might be necessary to convert primary semicircular canal afferent response dynamics to central neuron ones.     

Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys.

1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prolonged reduction of motion sickness sensitivity by visual-vestibular interaction

The angular vestibulo-ocular reflex (aVOR) and optokinetic nystagmus (OKN) were elicited simultaneously at low frequencies to study effects of habituation of the velocity storage time constant in the vestibular system on motion sickness. Twenty-nine subjects, eleven of whom were susceptible to motion sickness from common transportation, were habituated by sinusoidal rotation at 0.017?Hz at peak velocities from 5 to 20°/s, while they watched a full-field OKN stimulus. The OKN stripes rotated in the same direction and at the same frequency as the subjects, but at a higher velocity. This produced an OKN opposite in direction to the aVOR response. Motion sickness sensitivity was evaluated with off-vertical axis rotation (OVAR) and by the response to transportation before and after 5?days of visual-vestibular habituation. Habituation did not induce motion sickness or change the aVOR gains, but it shortened the vestibular time constants in all subjects. This greatly reduced motion sickness produced by OVAR and sensitivity to common transport in the motion susceptible subjects, which persisted for up to 18?weeks. Two motion susceptible subjects who only had aVOR/OKN habituation without being tested with OVAR also became asymptomatic. Normal subjects who were not habituated had no reduction in either their aVOR time constants or?motion sickness sensitivity. The opposing aVOR/OKN stimulation, which has not been studied before, was well tolerated, and for the first time was an effective technique for rapid and prolonged habituation of motion sickness without exposure to drugs or other nauseating habituation stimuli.     

Input to the vestibulo cerebellum and triceps brachii motoneurons during natural vestibular stimulation in frog

The response of cerebellar Purkinje cells and nerve triceps brachii was recorded in paralyzed frogs during natural vestibular stimulation. The response from about 63% of the Purkinje cells (mossy fiber input) recorded in the vestibulo cerebellum and of the triceps nerve during triangular wave roll oscillation consisted of activity increase during the ipsilateral side-down half of the cycle and decrease during the contralateral side-down half. It was shown that this activity, which originates partially from ipsilateral vertical canals, can be added to, or suppressed by, otolithic activity, depending on head position and direction rotation.The fact that the response of Purkinje cells was similar to that of triceps nerve implies that the vestibulo-cerebellum receives information of vestibular signals passing to the motor system. The characteristics of otolithic-canal interaction recorded in triceps nerve may explain the motor disturbances that result from lesions of otolithic receptors.