The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response

In the present study the optokinetic reflex, vestibulo-ocular reflex and their interaction were investigated in the mouse, using a modified subconjunctival search coil technique. Gain of the ocular response to sinusoidal optokinetic stimulation was relatively constant for peak velocities lower than 8°/s, ranging from 0.7 to 0.8. Gain decreased proportionally to velocity for faster stimuli. The vestibulo-ocular reflex acted to produce a sinusoidal compensatory eye movement in response to sinusoidal stimuli. The phase of the eye movement with respect to head movement advanced as stimulus frequency decreased, the familiar signature of the torsion pendulum behavior of the semicircular canals. The first-order time constant of the vestibulo-ocular reflex, as measured from the eye velocity decay after a vestibular velocity step, was 660 ms. The response of the vestibulo-ocular reflex changed with stimulus amplitude, having a higher gain and smaller phase lead when stimulus amplitude was increased. As a result of this nonlinear behavior, reflex gain correlated strongly with stimulus acceleration over the 0.1–1.6 Hz frequency range. When whole body rotation was performed in the light the optokinetic and vestibular system combined to generate nearly constant response gain (approximately 0.8) and phase (approximately 0°) over the tested frequency range of 0.1–1.6 Hz. We conclude that the compensatory eye movements of the mouse are similar to those found in other afoveate mammals, but there are also significant differences, namely shorter apparent time constants of the angular VOR and stronger nonlinearities.     

Influence of long-term optokinetic stimulation on eye movements of the rabbit

Two kinds of optokinetic afternystagmus (OKAN) have been studied in rabbits; positive and negative OKAN. Positive OKAN is the persistence of eye movements evoked by optokinetic stimulation following the termination of the stimulus, with the slow phase of the eye movements in the same direction as the inducing stimulus. Negative OKAN is evoked by long duration optokinetic stimulation, and has a slow phase of opposite direction to the inducing stimulus. The stimulus conditions which are optimal for inducing and maintaining negative OKAN were characterized. Rabbits were placed in an optokinetic drum for periods of 12-96 h (with appropriate intervening periods for food and water). Eye movements were recorded during and after the termination of optokinetic stimulation. The optimum optokinetic stimulus velocity for the induction of negative OKAN was 5 degrees/s. The minimum duration of stimulation for the induction of negative OKAN of maximum velocity was 48 h. Once induced, the slow phase of negative OKAN attained velocities of 50-100 degrees/s. Three conditions of restraint of the rabbits were studied after negative OKAN was induced during the intervening periods when eye movements were not being recorded. These conditions were: (1) unrestrained (full freedom of movement) without visual stimulation (in a dark enclosure); (2) restrained (horizontal head and body movement prevented) without visual stimulation; and (3) restrained with visual stimulation (in the stationary optokinetic drum). Conditions 1 and 2 caused negative OKAN to dissipate within 24 h. Condition 3 caused negative OKAN to be maintained for more than 70 h. The velocity imbalance of the horizontal vestibuloocular reflex (HVOR) was measured at different times following the induction of negative OKAN. It provided a more sensitive index of the central imbalance which caused negative OKAN, than did spontaneous nystagmus. One of the consequences of optokinetic stimulation measured over a 16 h period was a decrease in the gain of the optokinetic reflex. This reduction in gain could represent a central adaptation to maintained stimulation which in the absence of continued optokinetic stimulation is expressed as a nystagmus.     

The vestibulo-ocular reflex in the cat during linear acceleration in the sagittal plane

The horizontal and vertical components of the vestibulo-ocular reflex (VOR) were recorded in alert cats that were rotated with their head placed on or 45 cm eccentric from the axis of rotation. During off-axis rotation there was a centripetal acceleration along the animal's naso-occipital axis that changed the direction and the magnitude of the resultant otolith force in the animal's sagittal plane. When the animal was upright and eccentric from the axis of rotation, the horizontal VOR (HVOR) had a shorter time constant and smaller amplitude compared to the on-axis HVOR. The effect was symmetrical for both directions of the naso-occipital linear acceleration. When the animal was on its side and faced away from the axis of rotation, there was a decrease in the time constant of the down VOR. When the animal faced the opposite direction, the down VOR time constant was increased. No statistically significant effect was found on the amplitude of the VVOR and the time constant of the up VOR.     

Effects of optokinetic velocity and medial vestibulo-cerebellum lesions on vestibulo-ocular reflex direction adaptation in the cat

Adaptive horizontal vestibulo-ocular reflex eye movements in response to vertical (pitch) rotations were produced by exposing three cats to synchronized horizontal optokinetic and vertical vestibular oscillations at 0.25 Hz. The effects of optokinetic stimulus velocity (6–80°/s peak) and nodulo-uvular cerebellum lesions were studied. All optokinetic velocities elicited vestibulo-ocular reflex direction adaptation, though 6°/s stimuli were somewhat less effective. Restricted aspirations of cerebellar vermis lobules IX and X in two cats resulted in reduced but still clearly evident adaptation.     

Effects of α-noradrenergic substances on the optokinetic and vestibulo-ocular responses in the rabbit: a study with systemic and intrafloccular injections

The effects of microinjection of alpha-noradrenergic agonists and antagonists in the flocculus on the basic gain and adaptibility of vestibulo-ocular and optokinetic responses were investigated. A complementary, previous investigation had shown that the adaptation, but not the basic performance, of compensatory oculomotor responses were markedly influenced by beta-noradrenergic mechanisms in the flocculus. In contrast, the present experiments with bilateral, intrafloccular injections of phenylephrine, prazosin, clonidine and idazoxan failed to reveal any effect of alpha 1- or alpha 2-noradrenergic mechanisms on either basic performance or adaptation of compensatory eye movements. Intravenous administration of clonidine, however, reduced the gain of the optokinetic and vestibulo-ocular responses by about 70 and 50%, respectively, at dosages of 0.07 mg/kg. Recovery from this effect took about 1.5 h. A higher dosage of clonidine (0.7 mg/kg) had a similar, but longer lasting effect, and also markedly increased the frequency of spontaneous saccades. Intravenous administration of phenylephrine did not affect the oculomotor responses. It is concluded that the control of oculomotor responses is not susceptible to alpha-noradrenergic influences at the level of the flocculus, but that alpha 2-agonistic action inhibits these responses through an extra-floccular structure.     

Cholinergic and noradrenergic stimulation in the rabbit flocculus have synergistic facilitatory effects on optokinetic responses

A recent study (Exp. Brain Res., 85 (1991) 475-481) showed that injection of the cholinergic agonist carbachol into the cerebellar flocculi had a pronounced facilitatory effect on the gains of the optokinetic (OKR) and vestibulo-ocular (VOR) reflexes, suggesting a positive modulatory role of the cholinergic system in the flocculus. Because many behavioral and electrophysiological studies throughout the brain have revealed a functional relationship between acetylcholine (ACh) and noradrenaline (NA), the present study was undertaken to compare the effects of floccular injection of the ACh agonist carbachol, the beta-adrenergic agonist isoproterenol and the conjoint injection of both of these substances on the basic gain of the VOR and the OKR. Carbachol and isoproterenol both significantly raised the gain of the OKR, by 0.14 and 0.11 respectively. Neither of the two substances significantly affected the gain of the VOR in light or darkness. Conjoint injection of the same amounts of carbachol and isoproterenol resulted in an increase in the gain of the OKR by 0.29 without significant changes in the gains of the VOR in the light or in darkness. These results suggest a synergistic and positive modulatory role of ACh and NA in the flocculus.     

The influence of age on optokinetic nystagmus

Summary The influence of age on optokinetic nystagmus (OKN) was studied in 63 healthy subjects, who were divided into three groups according to their age, group I (20–39 years), 11 (40–59 years) and III (60–82 years). It was found that on average maximal OKN velocity decreases considerably with age, from 114°/s in group I to 93°/s in group II and 73°/s in group III.Two mechanisms participate in the generation of OKN, the so-called fast component and velocity storage component. The fast component leads to immediate changes in slow phase nystagmus velocity and is related to smooth pursuit eye movements. The velocity storage component causes more gradual velocity changes and expresses itself during optokinetic afternystagmus (OKAN). To study the relative contribution of these two components, maximal smooth pursuit and OKAN velocity were determined in addition to the maximal OKN velocity for the same individuals. It was found that both smooth pursuit and OKAN performance decrease with age. Consequently the maximal OKN velocity, which depends on both factors, is even more affected than smooth pursuit eye movements.Supported by Deutsche Forschungsgemeinschaft SFB 200, A2     

Dependence of cat vestibulo-ocular reflex direction adaptation on animal orientation during adaptation and rotation in darkness

Four series of experiments investigated how adaptive changes in direction of the cat's vestibulo-ocular reflex (VOR) vary with position of the animal during adaptive training and postadaptive testing. In all experiments VOR was measured electrooculographically during rotations about earth-horizontal and vertical axes in the dark before and after 2 h of adaptation in which 0.25 Hz sinusoidal whole body rotation about a horizontal/vertical axis was paired with synchronous 0.25 Hz rotation of a visual pattern about a vertical/horizontal axis, respectively. In upright sagittal (US) experiments, coupling of pitch rotation with visual pattern rotation about an earth vertical axis yielded an adaptive horizontal VOR response to pitch rotation whose gain had a local maximum at 0.25-0.5 Hz plus a sustained rise for frequencies below 0.1 Hz. When post-tests were done with the animal rolled 90 degrees onto its side and rotated about the earth vertical axis (pitch relative to the cat), the low frequency rise was eliminated and the 0.25 Hz peak was reduced. In on side sagittal (SS) experiments, where training was done in the latter (on side) position, training produced only the 0.25 Hz peak without the low frequency rise, indicating that the rise is due to coupling of otolith input to horizontal VOR. Again the 0.25 Hz peak was reduced when testing was done with the cat oriented 90 degrees from the training position (in the US position). This indicates that the cross-coupled canal-ocular reflex response is modulated or gated by the position of the animal with respect to gravity.(ABSTRACT TRUNCATED AT 250 WORDS)     

GABAergic and glycinergic inputs to the rabbit oculomotor nucleus with special emphasis on the medial rectus subdivision

Contradictory results have been reported about the inhibitory input to the medial rectus subdivision of the oculomotor nucleus of the cat. In the present ultrastructural study, we quantified the GABAergic and glycinergic terminals in the various subdivisions of the rabbit oculomotor nucleus with the use of post-embedding immunocytochemistry combined with retrograde tracing of horseradish peroxidase. The density of the GABAergic input to the medial rectus subdivision was as substantial as that to the other subdivisions and the postsynaptic distribution of the GABAergic and glycinergic innervation did not differ among the different oculomotor subdivisions.     

Horizontal and vertical vestibulo-ocular and cervico-ocular reflexes in the monkey during high frequency rotation

In the alert monkey the horizontal vestibulo-ocular reflex (VOR) is basically compensatory over the range of 0.5 to 6 Hz with a gain near unity, and with the phase of the compensatory eye position having a minimal lag with respect to head position. Typical frequency-dependent eye movement patterns were observed. Vertical VOR is also compensatory having the same phase relations but with a reduced gain (-2.5 to -3.7 dB). In this range, vestibular input appears to be the predominant sensory influence on reflex eye movements. Additional optokinetic reflexes do not improve the VOR above 0.5 Hz. The horizontal cervico-ocular reflex (COR) is minimal or absent in normal monkeys.     

The alternation of optokinetic responses driven by moving stimuli in humans

When the two eyes were exposed dichoptically to two oppositely moving patterns, the alternating OKN was elicited, in which the eye movements tracked the two moving stimuli alternately. In the present experiment, two oppositely moving stimuli were periodically exchanged between the eyes, the results showed that the alternation of OKN direction was not affected by this exchange. It suggests that alternating OKN was not controlled by rivalry between the two eyes but between two perceived motion patterns.     

The horizontal and vertical cervico-ocular reflexes of the rabbit

Horizontal and vertical cervico-ocular reflexes of the rabbit (HCOR, VCOR) were evoked by sinusoidal oscillation of the body about the vertical and longitudinal axes while the head was fixed. These reflexes were studied over a frequency range of 0.005–0.800 Hz and at stimulus amplitudes of± 10°. When the body of the rabbit was rotated horizontally clockwise around the fixed head, clockwise conjugate eye movements were evoked. When the body was rotated about the longitudinal axis onto the right side, the right eye rotated down and the left eye rotated up. The mean gain of the HCOR (eye velocity/body velocity) rose from 0.21 and 0.005 Hz to 0.27 at 0.020 Hz and then declined to 0.06 at 0.3 Hz. The gain of the VCOR was less than the gain of the HCOR by a factor of 2–3. The HCOR was measured separately and in combination with the horizontal vestibulo-ocular reflex (HVOR). These reflexes combine linearly. The relative movements of the first 3 cervical vertebrate during stimulation of the HCOR and VCOR were measured. For the HCOR, the largest angular displacement (74%) occurs between C₁ and C₂. For the VCOR, the largest relative angular displacement (45%) occurs between C₂ and C₃. Step horizontal clockwise rotation of the head and body (HVOR) evoked low velocity counterclockwise eye movements followed by fast clockwise (resetting) eye movements. Step horizontal clockwise rotation of the body about the fixed head (HCOR) evoked low velocity clockwise eye movements which were followed by fast clockwise eye movements. Step horizontal clockwise rotation of the head about the fixed body (HCOR + HVOR) evoked low velocity counterclockwise eye movements which werenot interrupted by fast eye clockwise movements. These data provide further evidence for a linear combination of independent HCOR and HVOR signals.     

The effect of alcohol on cervical and ocular vestibular evoked myogenic potentials in healthy volunteers

ObjectiveWe investigated the effect of alcohol on the cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs). As alcohol produces gaze-evoked nystagmus (GEN), we also tested the effect of nystagmus independent of alcohol by recording oVEMPs during optokinetic stimulation (OKS).MethodsThe effect of alcohol was tested in 14 subjects over multiple rounds of alcohol consumption up to a maximum breath alcohol concentration (BrAC) of 1.5‰ (mean 0.97‰). The effect of OKS was tested in 11 subjects at 5, 10 and 15 deg/sec.ResultsoVEMP amplitude decreased from baseline to the highest BrAC level by 27% (range 5–50%, P < 0.001), but there was no significant effect on oVEMP latency or cVEMP amplitude or latency. There was a significant negative effect of OKS on oVEMP amplitude (16%, P = 0.006).ConclusionsWe found a selective effect of alcohol on oVEMP amplitude, but no effect on the cVEMP. Vertical nystagmus elicited by OKS reduced oVEMP amplitude.SignificanceAlcohol selectively affects oVEMP amplitude. Despite the effects of alcohol and nystagmus, both reflexes were reliably recorded in all subjects and conditions. An absent response in a patient affected by alcohol or nystagmus indicates a vestibular deficit.     

Control of human optokinetic nystagmus by the central and peripheral retina: Effects of partial visual field masking, scotopic vision and central retinal scotomata

Optokinetic nystagmus (OKN) was elicited in humans by a horizontally moving grating covering the whole visual field. Selective stimulation of central or peripheral parts of the retina was achieved by partial masking or scotopic viewing conditions in normals; three patients with a unilateral central retinal scotoma were studied in addition. In all cases, the elimination of foveal stimulation was accompanied by a decrease in OKN slow phase velocity compared to whole field stimulation. Vertical masks with retinally stabilized edges were used to selectively occlude or stimulate central or peripheral sectors with a fixed retinal location. A central stimulus was always more effective than the complementary peripheral stimulus, until the central zone was narrowed down to a width of 5-10 degrees. This central dominance was found throughout the range of velocities (6-180 degrees/s) and spatial frequencies (0.05-0.5 cycles/deg) used. A horizontal central band of occlusion caused a smaller decrease of OKN than a vertical occlusion with the same width. Scotopic vision caused a uniform mild decrease in OKN gain throughout the velocity range, provided that the spatio-temporal frequency of the stimulus remained within the scotopic resolution range. The patients had a slightly lower OKN gain when viewing with the scotomatous eye than with the contralateral, normal eye. The normal slight preference for temporal-to-nasal motion was not accentuated by masking or scotopic vision in normal eyes, but was enhanced in the eyes with the pathological scotomata in two of the three patients. All responses were immediate; no slow build-up was seen under any condition.     

The abducens motor and internuclear neurons in the rabbit: retrograde horseradish peroxidase and double fluorescent labeling

Horseradish peroxidase and the fluorochromes Fast blue and propidium iodide were injected into the lateral rectus and retractor bulbi muscles and/or the oculomotor nucleus of the rabbit to determine the locations and basic morphology of motoneurons and internuclear neurons in the abducens nucleus. The 1000–1100 motoneurons found were distributed throughout the nucleus except in the rostral and caudal tips, but were most densely clustered in the dorsomedial area, especially in the middle third of the nucleus, where 60% of these cells were found. The rostral and caudal tips were composed of internuclear neurons, 25% of which lay in the rostral third of the nucleus, 35% in the middle third and 40% in the caudal third. In the middle third, interneurons occupied the ventral and lateral areas of the nucleus (where they mingled with motoneurons); in the rostral and caudal thirds they were more widely distributed. At the level of the caudal half of the nucleus it was impossible to distinguish clearly between the most lateral abducens interneurons and the most rostromedial labeled vestibular neurons. The abducens interneurons of the rabbit (320–380) thus differ in interesting respects from those described previously in either lateral eyed or frontal eyed mammals.     

Changes in the horizontal vestibulo-ocular reflex of the rhesus monkey with behavioral and pharmacological alerting

It is well known that eye movements are influenced by an animal's state of arousal. Alterations in the dynamic characteristics of the horizontal vestibulo-coular reflex of adolescent rhesus monkey induced by changes in the animal's state of arousal were studied using linear system analysis employing both single frequency sinusoidal and white noise rotational stimulations. Arousal changes were induced by a behavioral task and/or the administration of amphetamines (0.5 mg/kg). Results indicate that highly alert animals display vestibulo-ocular reflex gains significantly different from less alert animals. Specifically, the gain of the vestibulo-ocular reflex is closer to unity over a wider range of frequencies in more alert animals. These changes were independent of the method used to maintain a high level of arousal.     

Physiological properties of the output neurons in the deep layers of the superior colliculus of the rabbit

Using antidromic and orthodromic stimulation techniques, we studied physiological properties of the output neurons in the deep layers of the superior colliculus (SC) of 34 New Zealand rabbits. SC cells antidromicaly activated from the contralateral predorsal bundle (PDB) could also be activated by stimulation of the contralateral SC and ipsilateral central lateral nucleus of the thalamus (CL). The majority of these output neurons responded predominantly to the stimulation of the optic nerve, and only a small proportion of the output neurons were responsive to the stimulation of somatosensory and auditory (and/or vestibular) nerves. These results suggest that the orienting reflex might be elicited mainly by visual afferents in the rabbit The output SC neurons were subject to a 70 ms inhibition after antidromic stimulation of the PDB and a 40 ms inhibition after transsynaptic (orthodromic) stimulation of the optic chiasm (OX), indicating that the output neurons in the deep layers of the SC might be subject to at least two inhibitory circuits. These results are discussed in the context of a putative saccadic suppression circuitry model.     

Trigeminal nerve-mediated reflex arterial blood pressure decrease and vasodilatation in lower lip of the rabbit

We measured the effects of electrical stimulation of the central cut end of the lingual nerve on lower lip blood flow (LBF) and on arterial blood pressure in urethane-anesthetized, artificially ventilated, cervically vagosympathectomized rabbits. Different effects were observed depending on the stimulus frequency. Increasing the stimulus frequency above 5 Hz produced progressively larger ipsilateral LBF increases until the optimal frequency was reached at 20 Hz. In contrast, stimulation at above 0.5 Hz evoked progressively larger decreases in both contralateral LBF and arterial blood pressure until the optimal frequency was reached at around 10 and 2 Hz, respectively. Thus, the optimal stimulus frequencies for the ipsilateral LBF increase and the arterial blood pressure decrease were widely different. The lingual nerve-evoked change (i.e., fall) in arterial blood pressure showed a significant correlation with the contralateral LBF decrease, but not with the ipsilateral LBF increase. Prior administration of hexamethonium at 10 mg/kg markedly reduced both the ipsilateral LBF increase and arterial blood pressure decrease, although it was more effective against the former than against the latter. Pretreatment with scopolamine (muscarinic-receptor antagonist, 0.1 mg/kg), phentolamine (alpha-adrenoceptor antagonist, 0.1 mg/kg), or propranolol (beta-adrenoceptor antagonist, 0.1 mg/kg) failed to affect either response. However, 1.0 mg/kg phentolamine significantly reduced both responses (P<0.05). These results indicate that, in the rabbit, the LN-evoked reflex increase in ipsilateral LBF is (a) largely independent of any concomitant arterial blood pressure change and (b) probably due to active vasodilatation mediated via parasympathetic mechanisms. In contrast, the evoked decrease in contralateral LBF was proportional to the decrease in arterial blood pressure, suggesting that the former was secondary to the latter.     

Ocular vestibular evoked myogenic potentials: The effect of head and body tilt in the roll plane

ObjectiveTo explore effects of whole-head/body tilt in the roll plane on ocular-vestibular evoked myogenic potentials (oVEMP).MethodsTwenty healthy subjects were randomly tilted in an Eply Omniax rotator across a series of eight angles from 0° to 360° (at 45° separations) in the roll plane. At each position, oVEMPs to air-conducted (AC) and bone-conducted (BC) stimulation were recorded from unrectified infra-orbital surface electromyography during upward gaze. oVEMP amplitudes, latencies and amplitude asymmetry were compared across each angle of orientation.ResultsHead orientation had a significant effect on oVEMP reflex amplitudes for both AC and BC stimulation (p < 0.001). For both stimuli there was a trend for lower amplitudes with increasing angular departure from the upright position. Mean amplitudes decreased by 42.6–56.8% (AC) and 23.2–25.5% (BC) when tilted 180°. Roll-plane tilt had a significant effect on amplitude asymmetry ratios recorded in response to AC stimuli (p < 0.001), indicating a trend for lower amplitudes from the dependent (down) ear. Amplitude asymmetry ratios for BC stimuli were unaffected by head and body orientation.ConclusionsThe results confirm an effect of head and body orientation on oVEMP reflexes recorded in response to air- and bone-conducted stimuli.SignificanceThe upright position yields an optimal oVEMP response.