Brain Stem Omnipause Neurons and the Control of CombinedEye-Head Gaze Saccades in the Alert Cat

Martin Paré and Daniel Guitton

Montréal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montreal,Quebec H3A 2B4, Canada

    ABSTRACT
Abstract
Introduction
Methods
Results
Discussion
References

Paré, Martin and Daniel Guitton. Brain stem omnipause neurons and the control of combined eye-head gaze saccades in the alert cat. J. Neurophysiol. 79: 3060-3076, 1998. When the head is unrestrained, rapid displacements of the visual axis---gaze shifts (eye-re-space)---are made by coordinated movements of the eyes (eye-re-head) and head (head-re-space). To address the problem of the neural control of gaze shifts, we studied and contrasted the discharges of omnipause neurons (OPNs) during a variety of combined eye-head gaze shifts and head-fixed eye saccades executed by alert cats. OPNs discharged tonically during intersaccadic intervals and at a reduced level during slow perisaccadic gaze movements sometimes accompanying saccades. Their activity ceased for the duration of the saccadic gaze shifts the animal executed, either by head-fixed eye saccades alone or by combined eye-head movements. This was true for all types of gaze shifts studied: active movements to visual targets; passive movements induced by whole-body rotation or by head rotation about stationary body; and electrically evoked movements by stimulation of the caudal part of the superior colliculus (SC), a central structure for gaze control. For combined eye-head gaze shifts, the OPN pause was therefore not correlated to the eye-in-head trajectory. For instance, in active gaze movements, the end of the pause was better correlated with the gaze end than with either the eye saccade end or the time of eye counterrotation. The hypothesis that cat OPNs participate in controlling gaze shifts is supported by these results, and also by the observation that the movements of both the eyes and the head were transiently interrupted by stimulation of OPNs during gaze shifts. However, we found that the OPN pause could be dissociated from the gaze-motor-error signal producing the gaze shift. First, OPNs resumed discharging when perturbation of head motion briefly interrupted a gaze shift before its intended amplitude was attained. Second, stimulation of caudal SC sites in head-free cat elicited large head-free gaze shifts consistent with the creation of a large gaze-motor-error signal. However, stimulation of the same sites in head-fixed cat produced small "goal-directed" eye saccades, and OPNs paused only for the duration of the latter; neither a pause nor an eye movement occurred when the same stimulation was applied with the eyes at the goal location. We conclude that OPNs can be controlled by neither a simple eye control system nor an absolute gaze control system. Our data cannot be accounted for by existing models describing the control of combined eye-head gaze shifts and therefore put new constraints on future models, which will have to incorporate all the various signals that act synergistically to control gaze shifts.

    INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References

Brain stem circuits that control saccadic eye movements contain neurons whose tonic activity ceases, or pauses, before and during saccades of any direction or amplitude (in monkey: Cohen and Henn 1972; Keller 1974; Luschei and Fuchs 1972; in cat: Evinger at al. 1982; King et al. 1980; Paré and Guitton 1994a). These "omnipause" neurons (OPNs) are located in the nucleus raphe interpositus of the caudal pontine reticular formation (Büttner-Ennever et al. 1988) and have been shown to contact brain stem areas containing premotor "burst" neurons that drive saccades (Büttner-Ennever and Büttner 1978; Langer and Kaneko 1983; Ohgaki et al. 1987, 1989; Strassman et al. 1987) with inhibitory projections (Curthoys et al. 1984; Furuya and Markham 1982; Horn et al. 1994; Nakao et al. 1980, 1988). The release of this inhibitory signal thus allows the activation of the saccade burst generator. The potent inhibitory gating of OPNs on the saccade burst generator is clearly demonstrated by the suppression of all saccades during electrical microstimulation of the OPN area (Becker et al. 1981; Evinger et al. 1982; Keller 1974, 1977; King and Fuchs 1977).

Previous studies have focused on OPN responses in relation to saccadic eye movements in animals whose head is restrained (head-fixed). When the head is unrestrained (head-free), as in everyday life, displacements of the visual axis (henceforth called gaze shifts) are accomplished by coordinated eye and head movements. How the brain controls and coordinates the two individual mobile segments to generate a gaze shift is a much-debated question. In this paper, the role of OPNs will be considered in this context.

Neurophysiological evidence indicates that neurons in the intermediate layers of the superior colliculus (SC) play an important role in generating rapid orienting gaze shifts. In cat, identified collicular efferent neurons projecting to brain stem premotor burst circuits appear to carry a signal representing gaze motor error, the difference between desired and actual gaze positions (Munoz and Guitton 1991; Munoz et al. 1991). Electrical stimulation of the caudal part of the cat SC elicits gaze shifts composed of both eye and head movements (Paré et al. 1994; Roucoux et al. 1980). In comparison, electrical stimulation of the rostral pole of the SC (an area postulated to control fixation behavior) (Munoz and Guitton 1989, 1991; Munoz et al. 1991; Munoz and Wurtz 1993; Peck 1989; Peck and Baro 1997) interrupts ongoing gaze shifts in the head-free cat (Paré and Guitton 1994b).

OPNs receive an important projection from the rostral "fixation" area of the SC (Büttner-Ennever and Horn 1995; Paré and Guitton 1994b), thereby suggesting that the collicular contribution to fixation behavior is mediated via OPNs and that SC fixation-related neurons and OPNs possess similar discharge characteristics with respect to gaze shifts. In the head-free cat, efferent neurons from the SC fixation area stop discharging during gaze shifts (Munoz et al. 1991), and our preliminary observations (Paré and Guitton 1990) showed that OPNs also pause for the duration of gaze shifts. In the present study, we analyzed in detail OPN pause characteristics associated with natural active head-free gaze shifts. In addition, we investigated the responses associated with perturbed gaze shifts as well as those evoked by electrical stimulation of the caudal regions of the SC in the head-fixed and the head-free conditions. The rationale for these experiments is as follows. If a 70° gaze shift is required from a cat whose head is immobilized shortly before the movement, the animal (partially because of its limited oculomotor range, ±25°) will generate a saccade of only 15° in amplitude (Guitton et al. 1984). In this condition, the SC presumably requests a 70° gaze shift, which cannot be completed. How will OPNs respond to such a gaze trajectory perturbation? Similarly, electrical stimulation applied to the intermediate layers of the caudal part of the SC in the head-fixed cat elicits eye saccades whose vectors do not conform to the retinotopically coded motor map revealed by both single-neuron recording (Munoz and Guitton 1991; Munoz et al. 1991) and head-free stimulation (Paré et al. 1994). These saccades are directed to a "goal" in the orbit (i.e., they are craniotopically coded), which is located ~15° relative to the primary position in the same direction as the gaze vectors evoked head-free (Guitton et al. 1980; McIlwain 1986; Paré et al. 1994). Hence, for a given caudal SC output, quite different motor responses are produced depending on initial eye position and on whether or not the head is free to move. In this context, it is important to know whether OPN responses are related to the SC output (presumed to be a constant gaze-motor-error signal) or by the resulting movement: will OPN pause duration be equal to or longer than the duration of the 15° craniocentric eye saccade? Only if the pause is prolonged past the eye saccade end can the OPNs pause be considered controlled by a still present gaze-motor-error signal. To complement these studies, we activated OPNs by electrical stimulation to determine the effect on the eye and head components of gaze shifts.

Regarding the control of OPN pause duration, an important question arises as to the role of mechanisms independent of the presumed SC-mediated gaze control signals. The fact that OPNs pause during the quick phases of vestibular nystagmus induced by passive head rotation (even though these rapid eye movements can be generated without the SC) (Flandrin and Jeannerod 1981; Hepp et al. 1993; Schiller et al. 1980) suggests that mechanisms for initiating and stopping rapid eye (or gaze) movements are also situated downstream of the SC. To gain further insights into this putative mechanism, we recorded from OPNs during passive gaze shifts induced by either whole-body rotation or head rotation about the stationary body.

In general, our results indicate that cat OPNs pause for the duration of gaze shifts irrespective of the eye-in-head trajectory and regardless of how the gaze shifts are generated: either actively or passively, or by SC stimulation. However, if the head is prevented from moving and a large gaze shift is requested, either naturally or by stimulation of the caudal SC, OPNs pause only for the eye movements, which themselves do not reach the amplitude of the intended gaze shift. Brief descriptions of parts of these studies have appeared in abstract form (Guitton et al. 1991; Paré and Guitton 1989).

    METHODS
Abstract
Introduction
Methods
Results
Discussion
References

Animal preparation

A total of 10 adult cats (referred in the text as A, B, C, G, P, R, S, V, W, and Y) were used in this study. Surgery was performed under aseptic conditions. Anesthesia was induced with ketamine hydrochloride (10 mg/kg im), and surgical levels of anesthesia were maintained using halothane inhaled through an endotracheal tube. A wire coil consisting of three turns of Teflon-coated multistrand stainless steel wire (California Fine Wire) was sutured to the sclera of one eye, and the leads led to a connector on the head explant. A recording chamber, constructed to hold a micropositioner (Kopf), was positioned just rostral to the lambdoid crest, centered on the midline and tilted 25° back from the frontal plane, to allow microelectrodes to access the brain stem through the cerebellum. In six cats, a stimulating electrode (rigid bipolar concentric electrode, Kopf SNEX-75) was placed in one (either left or right) VIth nerve where it exits from the brain (stereotaxic coordinates: P3.0-L3.0 mm) and implanted chronically. The connector for the eye coil, a head-holding device to restrain (if required) the head of the animal, and the recording cylinder were secured in place, embedded in a dental acrylic explant that was anchored to the skull with stainless steel bolts. A small post, also embedded in the explant, served to secure a second coil similar to the eye coil but now measuring the position of the head. At the end of the surgery, the animals received an intramuscular injection of gentamicin (15 mg/kg) or cefazolin (35 mg/kg) as a prophylactic measure against infection. These antibiotics were administered on a daily basis for 10 postoperative days. To alleviate any discomfort, animals were also given analgesic medication (buprenorphine hydrochloride, 0.01 mg/kg) during the postsurgical period. All animal care and experimental procedures were approved by the McGill University Animal Care Committee and were in accordance with the Canadian Council on Animal Care policy on use of laboratory animals.

Experimental procedures

During all the experiments, the alert animal was wrapped in a loosely fitting cloth bag and placed in a box that gently restrained its body and limb movements. The animal box was positioned on a turntable, which could be rotated in the horizontal plane. Depending on the experimental condition, the animal's head was either restrained by attaching the head-holding device to the recording table or left completely free to rotate from center, 90° left, right, and up, and 45° down, as permitted by the box structure. The positions of gaze and head relative to space were measured by the search-coil-in-magnetic-field technique (Robinson 1963). In the head-fixed cat, the eye coil measured the eye position relative to the head (eye-in-head). In the head-free cat, the eye-in-head signal was obtained by subtracting the head-coil signal from the signal of the eye coil, which then measured gaze position. Details of the coil system and the calibration procedures have been reported elsewhere (Guitton et al. 1984; Paré and Guitton 1994b).

Single-neuron activity was recorded extracellularly using either glass micropipettes (2-3 MOmega ) or tungsten microelectrodes (1-2 MOmega ; Frederick Haer). A hydraulic microdrive attached to the Kopf x-y micropositioner was used to advance electrodes into the brain. Details of the techniques used to record with glass micropipettes have been described in Guitton and Munoz (1991). For recording with tungsten microelectrodes, the electrode was manually advanced to ~5 mm above the IVth ventricle through a cannula (23-gauge hypodermic needle) that had punctured the dura. Action potentials were conventionally amplified, filtered (band-pass: 300 Hz to 10 kHz), displayed on an oscilloscope while being played on an audio monitor, and recorded for off-line analysis on an analog tape recorder (Vetter model D) in the early experiments and on a digital audio tape (DAT) recorder (TEAC RD-200T) in the later experiments.

The abducens nucleus was first localized by identification of neurons showing burst-tonic discharges and/or by antidromic field (or action) potentials elicited by electrical stimulation of the VIth nerve. We explored the region rostromedial and ventral to the abducens nucleus, where the vast majority of cat OPNs have been recorded previously (Evinger et al. 1982; Ohgaki et al. 1987; Strassman et al. 1987). The actual region from which we recorded OPNs in this study extended from the rostral margin of the abducens nucleus up to 1.2 mm anterior, 1.0-3.0 mm below the floor of the IVth ventricle, and ±0.6 mm lateral from the midline.

The activity of OPNs was recorded in different experimental conditions. Once a neuron was isolated, saccades having various directions were elicited to ascertain the omnidirectional characteristics of the pause in activity. The responses to saccadic eye movements in the head-fixed condition were generally tested first. Subsequently, the head of the animal was released from the head holder, and the animal was allowed to generate active combined eye-head gaze shifts to visual targets. If time permitted, the neuronal responses were recorded in other conditions.

ACTIVE MOVEMENTS. During these experiments, the alert head-fixed or head-free animal faced a tangent opaque barrier positioned at 40 cm from it and tracked a visual target that consisted of a small spoon, containing pureed cat food, that was protruded manually from behind to one side of the barrier (see Guitton et al. 1990; Munoz and Guitton 1991). The barrier width was adjustable to have the cat generate gaze shifts having a large range of amplitudes: from 5 to 80° (5 to 30° in the head-fixed condition). In general, a trial began with the target appearing on one side of the barrier at an eccentric position. The animal then aligned its gaze on the target that was displaced, after a variable delay, behind the barrier to reappear on the opposite side. The animal oriented to the target in the new position by executing a movement that crossed the central straight-ahead position. Although this experimental paradigm facilitates the generation of predictive movements, the occurrence of the latter was minimized by regularly changing the size and orientation of the barrier. We studied primarily horizontal movements.

PASSIVE MOVEMENTS. The discharges of some OPNs were studied during passively generated gaze shifts. In the first of these tests, the animal was positioned head-fixed on the turntable and was rotated en bloc, in either the light or dark, sinusoidally (0.2-0.5 Hz) in a horizontal plane about a vertical axis centered on the head at the level of the labyrinths. In the second of these tests, we imposed horizontal steplike position changes of the turntable that had trajectories similar to those made by the head in active combined eye-head gaze shifts. Last, we tested the responses of OPNs to horizontal steplike head rotations, but this time about a stationary trunk. To generate the latter head movements, the experimenter rotated manually the animal's head in the horizontal plane via the head holder.

In some experiments, OPNs were recorded while the animal had its head attached via a universal joint to a freely rotating shaft equipped with an electromagnetic brake (see Guitton et al. 1984). In this apparatus, the head motion of the animal was restrained mainly to the horizontal plane. The brake was applied randomly, triggered by a gaze-velocity threshold, during ongoing gaze shifts either actively initiated by the cat in response to a visual target or passively generated by the experimenter who rotated the animal's head about its stationary body. Trials in which head motion was perturbed were interspersed among regular unperturbed trials.

SC STIMULATION. For the preparation of these experiments, rigid bipolar concentric electrodes (Kopf SNEX-25) were implanted into the SC in a second surgical procedure, when the animal was slightly anesthetized (ketamine hydrochloride 10 mg/kg im, supplemented by 2-5 mg/kg). As described in a previous report (Paré and Guitton 1994b), the movement vectors represented in both SCs were mapped out, and stimulating electrodes were implanted chronically in the collicular deeper layers where electrical stimuli evoked eye movements with minimal threshold intensities.

A train of cathodal pulses generated by a stimulator (Grass S88) and constant-current stimulus isolation units (Grass PSIU6) was used to stimulate the SC when the animal's head was either restrained or unrestrained, and the activity of isolated OPNs was simultaneously recorded. Current intensity was monitored on an oscilloscope and was measured by taking the voltage across a 10-kOmega resistor in series with the stimulating electrode; it was adjusted to be two times the threshold current required to evoked a movement (at a frequency of 300 pulses/s) and ranged from 20 to 80 µA. Train duration was made long enough to assure a complete movement (Paré et al. 1994); it ranged from 200 to 800 ms. Pulse rate was constant within a train, but it ranged from 200 to 300 pulses/s between trains. Pulse duration was always 0.3 ms. In both the head-fixed and the head-free conditions, stimulation trains were delivered when the eye and gaze, respectively, were at different initial positions.

OPN STIMULATION. In two animals, a train of cathodal pulses was used to stimulate sites where OPNs were recorded. Current intensity ranged from 20 to 40 µA. The range of pulse rates was 100-300 pulses/s; train duration varied between 10 and 200 ms. Pulse duration was always 0.5 ms. The stimuli were applied during and around the onset of head-free gaze shifts made to visual targets.

Data collection and analysis

Neuronal activity and signals of gaze, head, and target positions were recorded on tapes. The neuronal activity signal recorded by the DAT recorder was sampled at 20 kHz and the position signals at 2.5 kHz. During off-line analysis, blocks of records were played back and digitized by a PDP-11/73 computer. Position traces were low-pass filtered at 250 Hz and sampled at 1 kHz. A time-amplitude window discriminator (Bak Electronics) isolated single-neuron activity and produced a logic pulse for each action potential that met amplitude and time constraints. In the case where OPN activity was recorded during SC stimulation, we routinely examined the quality of the discrimination of the action potentials with respect to the electrical stimulus artifact.

The digitized and calibrated data were displayed on a large oscilloscope screen in segments of 1-1.5 s. An interactive graphics program allowed the investigator to scroll through the data and to select sections to be analyzed. The analysis was restricted to head-fixed eye saccades and head-free gaze saccades made within 30° of the horizontal plane; in this section to be referred to simply as saccades. Movement velocity traces were derived from position traces using the fourth-order Runge-Kutta formula (Press et al. 1986). The beginning of a saccade was defined as the moment when the movement velocity exceeded 20°/s. The end of the saccade was determined as the time at which its velocity dropped below this level. Cursors were manually placed at these levels to define the start and end of saccades. Measurements were made on traces that were not additionally filtered.

The onset and end of the saccade-associated pause in activity were defined to be, respectively, the times of the last action potential preceding the pause and of the first action potential following it. The temporal relationships between the discharge of each neuron and the saccade was estimated by determining 1) the interval from the onset of the pause in activity to the beginning of the saccade, to be called the pause onset time and 2) the interval from the end of the pause to the end of the saccade, to be called the pause end time. Saccade trials exhibiting significant perisaccadic drifts in eye or gaze position were excluded from this analysis and considered separately. The data analysis was performed on 80486 IBM-compatible computer using several commercially available packages.

    RESULTS
Abstract
Introduction
Methods
Results
Discussion
References

Characteristics of OPN discharges during active movements

One hundred fourteen OPNs were recorded in 10 cats. These neurons were tonically active during intersaccadic intervals and exhibited a complete cessation of activity during saccadic eye and gaze movements made head-fixed and free, respectively. Figure 1, A and B, illustrates the pause in activity of one representative neuron (neuron C8) during two horizontal eye saccades made head-fixed. The characteristic saccade-related pause in discharge was omnidirectional: regardless of saccade direction, the neuron ceased discharging before the onset of the saccade and resumed its discharge near the time of saccade completion.


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FIG. 1. Saccade-related pauses in activity of 1 representative omnipause neuron (OPN; neuron C8) recorded in the head-fixed (A and B) and the head-free (C and D) condition. For each panel: top, spike activity, each tick mark represents an action potential; middle, vertical (Ev) and horizontal (Eh) eye position traces (A and B) or gaze (G), head (H), and eye (E) position traces in the horizontal plane (C and D); bottom, instantaneous discharge rate (1/interspike interval). Vertical dotted lines indicate, respectively, the beginning and end of the pause in the neuron's activity. Upward deflections indicate rightward and upward movements. Arrow indicates the end of the eye saccade in the orbit.

Of the 114 OPNs, 52 in the 10 cats were recorded for long enough periods when the animal's head was unrestrained that the characteristics of their activity could at least be partially analyzed. Figure 1, C and D, shows examples of the discharge behavior of neuron C8 during two large combined eye-head gaze saccades. In these movements, the beginning of a gaze shift coincided with the start of the rapid eye movement, but the gaze displacement often terminated well after the end of the rapid portion of the eye movement, to be referred to as the eye saccade (Guitton et al. 1984, 1990). At the end of the eye saccade, but before gaze motion ceased, the eye started either to move back in a compensatory direction (Fig. 1C) or remained immobile in the orbit, within the oculomotor range of the animal, during the so-called "plateau" phase (Fig. 1D) (Guitton et al. 1984; see also Becker and Jurgens 1992; Guitton and Volle 1987; Laurutis and Robinson 1986; Phillips et al. 1995; Tomlinson and Bahra 1986). All OPNs responded with a cessation of activity during the entire duration of head-free gaze shifts, i.e., the OPN pause often outlasted the eye saccade end (Fig. 1, C and D, arrow), but always terminated with the end of the gaze shift. The presence of plateau phases in the eye trajectory, during which eye velocity was near zero (Fig. 1D), allowed a clear discrimination between the duration of the eye saccade and the duration of the gaze displacement. In such gaze shifts, OPNs were always found to resume discharging not when the eye had achieved a stationary position in the orbit, but only when the gaze shift was completed. Figure 2, A-F, emphasizes this characteristic in greater detail for the same neuron C8. Figure 2, A and B, shows, for the head-fixed condition, how the OPN pause is time locked to eye saccade start and end, respectively. Figure 2, C-F, illustrates head-free results in which 1) we aligned the neuronal activity on the end of the associated eye (Fig. 2C) or gaze saccades (Fig. 2D) or 2) we aligned the position traces of eye movements (Fig. 2E) and corresponding gaze shifts (Fig. 2F) on the first action potential at the end of the pause in activity. The latter procedure eliminates potential interpretation problems linked to the determination of movement end. From this analysis, it is clear that the end of the head-free gaze shifts coincides best with the pause end and that the eye in the orbit often attained a maximum eccentric position and counterrotated before the pause end. Results were qualitatively similar in the 51 other OPNs we recorded in the head-free condition; quantitative results were available for 25 of these (see next 2 sections).


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FIG. 2. A and B: examples of discharge behavior exhibited by 1 OPN (neuron C8) in relation to 8 horizontal saccadic eye movements made head-fixed toward a visual target. Tick marks on each horizontal line (raster) represent action potentials. Each line shows activity associated with 1 saccade. Neuronal activity aligned on the start (A) and end of saccades (B). C and D: rasters and histograms of neuronal activity of neuron C8 aligned on either the end of 15 eye saccades (C) or the end of the corresponding 15 gaze saccades (D) in the head-free condition. E and F: series of the same eye and gaze saccades as in C and D, but now aligned on the end of the pause in activity of the same neuron, i.e., the 1st action potential after the pause. The eye and gaze traces are aligned on a single vertical position to facilitate comparison between traces.

Temporal relationships between OPN pauses and active movements

HEAD-FIXED CONDITION. Figures 1, A and B, and 2, A and B, show for the head-fixed condition how OPN pause onset and end are tightly linked to, respectively, eye saccade start and end. We had sufficient data (for each neuron, a minimum of 30 horizontal saccades of amplitudes ranging from 5 to 30°, with the majority being between 5 and 10°) in 51 of 114 OPNs in the 10 cats to analyze quantitatively their discharge during horizontal head-fixed eye saccades. Note that there was no correlation between saccade amplitude and the timing of the OPN pause in activity. Figure 3, A and B, illustrates, for each of these neurons, the mean time (±SD) from saccade start to pause onset and from saccade end to pause end. On average, the pause began ~22 ms before saccade start, and it ended nearly at saccade end (Table 1, top rows).


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FIG. 3. Temporal characteristics of OPN pause in activity. Time of pause onset from saccade start (A) and pause end from saccade end (B) for head-fixed eye saccades in 51 OPNs recorded in 10 cats. Time of the end of the OPN pause in activity relative to either the end of eye saccades (C) or the end of the associated gaze saccades (D) for 25 neurons in 7 head-free cats. Each filled circle and horizontal line corresponds to, respectively, the mean and SD calculated for a single neuron. The individual neuron data have been ranked, from top to bottom, in order of decreasing pause end time.

 
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TABLE 1. Temporal relationships of OPNs and horizontal eye and gaze saccades

HEAD-FREE CONDITION. We had sufficient data (for each neuron, a minimum of 30 horizontal gaze shifts of amplitudes ranging from 5 to 80°, with the majority being between 20 and 40°) in 25 of 52 OPNs, recorded in seven head-free cats (A, B, C, G, P, W, and Y), to analyze quantitatively their discharge during horizontal gaze shifts. For this sample of OPNs, the pause in activity began ~17 ms before the head-free gaze shifts (Table 1, top rows). Figure 3, C and D, illustrates, for each of these neurons, the mean value (±SD) of the end of the OPN pause relative to, respectively, the end of eye and gaze saccades. Recall that the end of the eye saccade is defined as the end of the rapid portion of the eye motion, i.e., when the eye velocity dropped below 20°/s (see METHODS). The pause ended 6.4 ms before the end of gaze shifts, but 29.6 ms after the eye saccades terminated (Table 1). The difference between the mean pause end time relative to head-free eye saccade end and gaze saccade end was highly significant (paired t-test, df = 24, t = 12.2, P < 0.0001).

COMPARISON BETWEEN HEAD-FIXED AND HEAD-FREE CONDITIONS. To test more objectively whether there were differences between head-fixed and head-free temporal relationships, we compared the pause onset and end times of 17 OPNs (recorded in 7 animals: A, B, C, G, P, W, and Y) for each of which we had sufficient data in both the head-fixed and the head-free conditions (Table 1, bottom rows). In this sample, the mean pause onset times for both head-free gaze (17.5 ms) and eye (18.2 ms) saccades were found to be statistically different from that of head-fixed eye saccades (22.2 ms; paired t-test, df = 16; gaze: t = 5.1, P < 0.0002; eye: t = 4.0, P < 0.001). The mean pause end time for head-free gaze saccades (6.1 ms) was weakly statistically different from that of head-fixed eye saccades (3.2 ms), and strongly different to that of head-free eye saccades (-31.4 ms) (paired t-test, df = 16; gaze: t = -2.3, P = 0.04; eye: t = 10.4, P < 0.0001). Thus the timing of the OPN pause with head-fixed saccades contrasted slightly with that relative to head-free gaze saccades, but much greater differences were observed for head-free eye-in-head saccades.

Relationship between OPN pause duration and active movement duration

HEAD-FIXED CONDITION. As has been described previously, the duration of the cessation of OPN discharge increased monotonically with the total duration of the concomitant saccadic eye movement. This can be predicted from the temporal relations shown in the previous section. Figure 4A is a scatter plot showing, for neuron C8, the relationship between eye saccade duration and pause duration in the head-fixed condition. Using linear regression, the data points (n = 219) were fitted with a line having a slope of 0.90 and a y-axis intercept of -4.4 ms (r = 0.99, t = 104.2, P < 0.0001). The linear regression lines of best fit for the duration-duration relationships for 51 OPNs, recorded in the 10 head-fixed cats, are shown in Fig. 4B. The range of saccade amplitudes used to quantify this relation was 5-30°. As with neuron C8, saccade duration was strongly correlated with pause duration: 84% (43/51) of the neurons had a correlation coefficient higher than 0.9, and the slope of the relations was close to unity. Table 2 (top rows) gives, for the sample, the mean values of the slope (0.86), the y-axis intercept (0.1 ms), and the correlation coefficient (0.95).


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FIG. 4. Relation between the duration of the pause in activity of OPNs and the duration of associated saccades. A and B: head-fixed condition. Data points and linear regression line for neuron C8 (A) and regression lines for 51 OPNs recorded from 10 cats (B). C and D: head-free condition. Data points and linear regression line for neuron C8 (C) and regression line for 25 OPNs recorded in 7 animals (D). , gaze saccades; ···, eye-in-head saccades.

 
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TABLE 2. Relationship between the duration of horizontal movements and the duration of the pause in activity of OPNs

HEAD-FREE CONDITION. Figure 4C shows a scatter plot through 291 data points, for neuron C8, of the relationship between pause duration and the duration of the associated horizontal gaze (open circle ) and eye (···) displacements in the head-free condition. For this neuron, and all others, the horizontal gaze saccades had amplitudes that ranged from 5 to 80°. With the use of linear regression, the slope, and y-axis intercept of the regression equations of neuron C8 were, respectively, 0.96 and -4.8 ms for gaze saccades (Fig. 4C, ; r = 0.99, t = 120.2, P < 0.0001) and 0.50 and 30.4 ms for eye saccades (Fig. 4C, ···; r = 0.82, t = 24.4, P < 0.0001). The lines of best fit for the duration-duration relationship for 25 OPNs, recorded in seven animals (cats A, B, C, G, P, W, and Y), are shown in Fig. 4D. The linear relation between gaze and pause duration in the head-free condition was very similar to the relation observed between eye and pause duration in the head-fixed condition (Fig. 4, C and D, ; compare with Fig. 4, A and B). As shown in Table 2 (top rows), the mean value of the parameters in the regression equation for gaze was as follows: slope, 0.92; intercept, 2.4 ms; and correlation coefficient, 0.96. Eighty-eight percent (22/25) of the neurons had a correlation coefficient higher than 0.9. In contrast to the gaze relation and as exemplified in Figs. 1, C and D, 2, C-F, and 3, C and D, the duration of the pause was not equal to the duration of the rapid component of the eye movement in the orbit (Fig. 4D, ···). In this condition, the mean slope, intercept, and correlation coefficient were 0.49, 25.9 ms, and 0.80, respectively (Table 2, top rows). These parameters for head-free eye saccades were significantly different from those for gaze saccades (paired t-test, df = 24, t = 13.6, t = -7.5, and t = 11.2, P < 0.0001).

COMPARISON BETWEEN HEAD-FIXED AND HEAD-FREE CONDITIONS. Sufficient data were available for 17 of the 25 OPNs recorded in seven animals (A, B, C, G, P, W, and Y) to permit a comparison, for each neuron, of the duration-duration relationships for horizontal movements in both the head-fixed and the head-free conditions (Table 2, bottom rows). For this sample, the mean values of the slope, y-axis intercept, and correlation coefficient of the regression lines were, respectively, 0.91, 1.4 ms, and 0.95 for head-free gaze saccades, and 0.87, 2.5 ms, and 0.95 for head-fixed eye saccades. These numbers for head-free gaze saccades were not significantly different from the ones for head-fixed eye saccades (paired t-test, df = 16; slope: t = 1.6, P = 0.12; y-intercept: t = 0.3, P = 0.77; correlation coefficient: t = 0.4, P = 0.67). In contrast, the mean values of the slope, y-axis intercept, and correlation coefficient of the regression lines for head-free eye saccades (respectively, 0.49, 25.8 ms, and 0.80) were statistically different from those for head-fixed eye saccades (paired t-test, df = 16; slope: t = 10.3, P < 0.0001; y-intercept: t = 4.6, P < 0.0005; correlation coefficient: t = 6.9, P < 0.0001).

Characteristic of OPN discharges during perisaccadic slow movements

An interesting feature of the gaze control system is the occasional use, by cats, of multiple-step gaze shifts to attain a target (Guitton et al. 1984). Between these rapid sequential gaze shifts, the visual axis frequently continues to move at low velocity. In addition, single saccades performed head-fixed are sometimes preceded or followed by similar slow movements of the visual axis, instead of stable fixation. It has been hypothesized that the premotor signal underlying these perisaccadic slow movements is generated by SC efferent neurons (Lefèvre et al. 1994; Missal et al. 1993; Olivier et al. 1993). Such a SC control of slow movements may suggest that the latter are part of the saccadic gaze control system, and it is therefore important to determine the associated OPN discharges. Importantly, it should be kept in mind that the presence of these movements renders difficult the estimation of the start and end of a saccade.

In each of our cats, a few examples of these perisaccadic slow movements were observed in both the head-fixed and the head-free conditions. Figure 5 shows one example in the head-fixed condition (Fig. 5A) and one in the head-free condition (Fig. 5B). In general, when compared with the average discharge rate during stable fixation periods, the tonic activity was reduced during perisaccadic slow movements.


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FIG. 5. Responses of OPNs during perisaccadic slow movements. A: head-fixed condition. B: head-free condition. In each panel: top trace, spike activity; bottom trace, instantaneous discharge rate; Ev and Eh, vertical and horizontal eye position traces in head-fixed condition. G, H, and E, horizontal gaze, head, and eye position traces in the head-free condition, respectively.

Influence of OPN activity on head motion

We tested the hypothesis that the activity of OPNs has an influence on head motion by 1) artificially increasing the activity of OPNs via electrical stimulation delivered during gaze shifts when these neurons were silent and 2) examining the head trajectory at the time that OPNs naturally resumed their discharge at the end of gaze shifts.

EFFECTS OF OPN STIMULATION. We applied microstimulation at sites where OPNs were recorded in two head-free animals (cats B and R). On random trials, the stimulation train, triggered by gaze saccade onset, was delivered to the OPN area during an ongoing gaze shift. Stimulation was found to interrupt transiently both eye and head, and therefore gaze movements (Fig. 6, A and B): the trajectory of both gaze and head displacements exhibited a clear deceleration a short time after the onset of the electrical stimulus. Because the head motion was not entirely stopped, the eye-in-head usually counterrotated during stimulation; the vestibuloocular reflex must then have been active. Head deceleration was also seen less frequently than gaze deceleration, perhaps due to the smoothing effects of head inertia. The mean latency from stimulation onset to deceleration of gaze and head movements was, respectively, 10 ± 8 ms (mean ± SD; n = 38) and 44 ± 11 ms (n = 36) for cat B, and 13 ± 5 ms (n = 51) and 36 ± 8 ms (n = 25) for cat R. The average latency for the two animals was 12 ms for gaze and 40 ms for the head. Figure 6C shows the effects when the OPN stimulation train occurred slightly before the initiation of gaze shifts. In these trials, stimulation also decelerated the initial portion of both gaze and head movements.


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FIG. 6. A and B: brief electrical stimulation delivered to the OPN area during ongoing eye-head gaze saccades interrupts momentarily both eye and head movements. Leftward (A) and rightward (B) gaze saccades made to visual targets. Stimuli were 50 µA at 300 pulses/s for 50 ms. Stimulated and nonstimulated trials are solid and dotted traces, respectively. Symbols G, H, E and G, &Hdot;, Ė are the position and velocity traces of gaze, head and eye, respectively, in the horizontal plane. C: OPN stimulation before eye-head gaze saccades decelerated the early motion of both gaze and head. Stimulus was 50 µA at 300 pulses/s for 50 ms.

EFFECTS OF OPN REACTIVATION. The movement of the head that accompanies a gaze saccade does not terminate with the completion of the gaze displacement. Thus head motion still occurs for a few hundred milliseconds, after pause end when OPNs are reactivated and gaze is stabilized (see Fig. 1, C and D). To investigate further the influence of OPN activity on head motion, we aligned the head velocity traces, obtained during several gaze shifts, on the time of occurrence of OPN reactivation. For all the gaze shifts examined in the 52 OPNs recorded in the head-free condition, the head attained its peak velocity and started to decelerate before the end of the gaze displacement. Thus the end of the pause occurred during head deceleration. We found that OPN reactivation never influenced the head trajectory; namely, the end of the pause was never associated with an increase in head deceleration.

Characteristics of OPN discharges during passive head movements

The activity of 24 OPNs in 6 cats (B, C, G, P, R, and S) was recorded during passively induced gaze displacements induced by pure vestibular stimuli obtained by sinusoidal whole-body rotations in the horizontal plane. Figure 7 illustrates the responses of neuron C8 in this condition. These stimuli induced the classic nystagmus pattern: a succession of smooth compensatory eye movements ("slow phases") stabilizing gaze position and rapid anticompensatory eye movements ("quick phases") contributing to gaze displacements. One interesting observation was that, occasionally, the rapid eye movement was followed by a plateau phase during which the eye remained immobile in the orbit while the animal was still rotating (Fig. 7, asterisk). In this situation, the OPN continued its pause during the gaze displacement due to head motion only. For all 24 OPNs, the relationship between the pause duration and the duration of the concomitant rapid gaze exhibited a strong linear relation. For neuron C8, the relation had a slope of 0.99 and an intercept of 8.8 ms (r = 0.99). This relation was very similar to that observed for active head-fixed eye saccades (Fig. 4A) and head-free gaze shifts (Fig. 4C). In contrast to the gaze relation, the duration of the pause was not always equal to the duration of the rapid component of the eye movement in the orbit (for neuron C8: slope = 0.66, intercept = 30.2 ms, r = 0.90). For each OPN (n = 24) that was recorded during such "gaze displacement phases" of vestibular nystagmus, we observed an activity pattern similar to that illustrated for neuron C8.


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FIG. 7. Responses of 1 OPN (neuron C8) during vestibularly induced gaze shifts in the dark, obtained by subjecting the animal to sinusoidal horizontal whole-body rotation (±60° at 0.2 Hz). From top to bottom: neuron's spike activity, each vertical bar represents an action potential; table position (T); horizontal gaze position (G); vertical (Ev) and horizontal eye position (Eh); neuron's instantaneous discharge rate. Vertical dotted lines indicate, respectively, the beginning and end of the pause in the neuron's activity. Upward deflection on traces indicates movements up and to the right, respectively. Arrow indicates the end of the eye saccade in the orbit for the gaze displacement labeled with an asterisk (see text).

Fourteen neurons in four animals (cats C, G, P, and S) were tested in response to rapid, steplike, whole-body rotations that mimicked natural orienting head movements. The responses displayed by two OPNs are shown in Fig. 8. Nystagmic eye movements were again usually induced (Fig. 8A), but eye position plateaus (Fig. 8B), similar to those observed in active gaze shifts, were more frequently observed than during low-frequency sinusoidal rotation. Also, we occasionally observed an absence of anticompensatory eye motion during a gaze shift (Fig. 8C). Consistent with all observations described above, the pause in activity of all the 14 OPNs recorded was invariably time locked to gaze shift duration.


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FIG. 8. Examples of OPN responses during horizontal step "en bloc" rotation in the dark. Top trace: spike activity. Bottom trace: instantaneous firing frequency; symbols G, T, E are the position traces of gaze, table, and eye in the horizontal plane, respectively.

The discharge behavior of 24 OPNs in 5 cats (B, C, G, P, and S) was also studied during passive horizontal gaze shifts generated by rapid rotation of the animal's head about its stationary body (Fig. 9). The eye displacements induced by this stimulus were very variable in trajectory, as described previously (Cullen et al. 1993; Guitton et al. 1984); the term "quick phase" is hardly appropriate for these movements. The eye movement usually consisted of an initial smooth compensatory movement, which gradually diminished to zero velocity, followed by a subsequent anticompensatory eye motion of quite variable amplitude and velocity. These curious eye movement trajectories occurred much more frequently in this paradigm than those induced by whole-body rotations as exemplified in Fig. 8. For all the 24 OPNs recorded during such passive head-on-body movements, the pause duration was much better correlated to the duration of the gaze shifts than to the duration (if even it could be measured, e.g., Fig. 9B) of the anticompensatory eye motion.


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FIG. 9. Examples of OPN responses during passive head rotation about stationary body.

Characteristics of OPN discharges during SC-induced movements

We recorded the activity of 13 OPNs in 3 cats (G, V, and Y) during gaze shifts elicited by electrical stimulation of the caudal SC. In the head-free condition, the stimulation evoked large gaze shifts with the typical pattern of eye and head motion observed for active gaze shifts (Fig. 10, A and B, compared with Fig. 1, C and D). Figure 10 illustrates the responses for two representative neurons (neuron G14, Fig. 10A; and neuron G15, Fig. 10B). OPNs paused for the duration of these gaze shifts and not for the duration of the eye saccade component. In the head-fixed condition, the direction and amplitude of the eye movements evoked by stimulating the same SC sites with identical parameters were systematically modified by initial eye position, i.e., the eye was directed to a particular region of the orbit (Fig. 11, inset). Figure 11, A-F, shows the associated neuronal activity of neuron G14. When such "goal-directed" eye saccades were evoked, the pause duration corresponded to the eye saccade duration: it did not continue past saccade end (Fig. 11, D-F). Most important, when the eyes were already at the craniotopic goal location and did not move when stimulation was applied, the OPN did not pause despite ongoing collicular stimulation (Fig. 11, A and B). Furthermore, when the initial eye position was extremely contralateral, electrical stimulation evoked a slow eye motion whose direction was ipsiversive; during this movement the OPN also did not pause (Fig. 11C). Results similar to those for neuron G14 were obtained for neuron G15 and the other 11 OPNs tested in this condition. These results indicate that the responses of OPNs were dictated by the motor response and not by the output of the SC that was presumably constant given the unchanging parameters of the electrical stimuli.


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FIG. 10. Responses of 2 OPNs (A: neuron G14; B: neuron G15) during gaze shifts elicited by stimulation of sites in the caudal portion of the superior colliculus in the head-free condition. Arrow indicates the end of the eye saccade in the orbit. Stimulus current intensity was 60 µA in A and 70 µA in B; pulse rate and train duration were 200 pulses/s and 400 ms, respectively.


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FIG. 11. Responses of one OPN (neuron G14) during electrical stimulation of the same caudal superior colliculus site as in Fig. 10A, but in the head-fixed condition. For each panel: top, vertical and horizontal eye positions; middle, action potentials; bottom, electrical stimulus. Inset: the trajectory of evoked saccades is projected onto the animal's frontal plane. Zero on x- and y-axis represents the straight-ahead position. Empty circles indicate the initial eye position. Filled circles are eye positions at which no movement was evoked. Eye positions were sampled at 1-ms intervals. Current was 60 µA, pulse rate was 200 pulses/s, and train duration ranged from 300 to 500 ms.

Responses of OPNs to head brake during gaze shifts

We recorded the activity of six OPNs in one animal (cat P) during gaze shifts, either passively or actively triggered, in which head motion was transiently interrupted by a mechanical clutch (head brake). The responses displayed by two of these OPNs are shown in Fig. 12. In the case of active movements, head motion was prevented just after an intended 40° gaze shift was initiated. In the typical cases illustrated in Fig. 12, A and B, the rapid portion of the eye movement, the eye saccade, ended shortly after the head motion ceased, and gaze continued moving slowly during the 180-ms period the head was immobilized. The pause associated with the onset of the gaze shift ended just before the first eye saccade terminated, i.e., after the start of the brake-induced head deceleration. Once the head was released, the gaze movement continued toward its goal. The activity ceased again just before the start of the gaze saccade after head release. In summary, in this paradigm OPNs paused during all saccadic gaze displacements and were reactivated during all intersaccadic periods including those caused by the head brake. This result is similar to that observed during SC stimulation and in which the OPN pause appeared strictly related to the motor response.


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FIG. 12. Responses of OPNs during gaze shifts within which the head motion was momentarily interrupted. A and B: visually guided gaze shifts. C: gaze shifts induced by passive head rotations on stationary body.

In the example of the braked passively induced gaze shift (Fig. 12C), the eye movement was highly variable, and, as shown in Fig. 9 (see also Cullen et al. 1993; Guitton et al. 1984), it was nearly impossible to distinguish rapid from slow phase eye movements. Just as in the active movements, the initial pause in OPN activity preceded the start of gaze motion and ended very shortly after the brake caused head motion to cease, which in turn ended gaze motion. Unlike braked active movements, the eye motion did not continue at low velocity when the head was immobilized. The OPN pause resumed at the onset of the small gaze shift that followed the release of the head, even though the eye was moving in a direction opposite to gaze.

    DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References

We have shown that, in a number of different experimental conditions, the duration of the pause in activity of OPNs is intimately related to the duration of saccadic gaze shifts executed by cats, but not to the duration of the associated rapid eye movements. These results support and extend our initial hypothesis that OPNs participate in gaze control (Paré and Guitton 1990). We discuss our data with respect to other studies and existing models regarding the discharge of OPNs in the various conditions studied here. We also suggest plausible mechanisms that can account for our data.

OPNs and head control

Our data suggest that OPN activity influences some neural elements involved in the generation of head movements. Electrical stimulation of OPNs affected head motion when delivered during a gaze shift. However, the natural OPN reactivation at the end of the pause left the head unaffected. This latter result concurs with the observation that the duration of the pause in OPN activity is not correlated with the duration of the head movement accompanying a gaze saccade (Paré and Guitton 1990; Phillips 1993).

Anatomic studies in the monkey have shown that very few OPNs project to the cervical cord (Robinson et al. 1994). No evidence has been provided for an OPN connection with reticular neurons involved in head movement control (Grantyn and Berthoz 1987; Phillips 1993). In comparison, the inhibitory projection of OPNs onto brain stem burst neurons is well documented, and it has been hypothesized that these neurons in cat form a gaze burst generator that drives both eye and head (Galiana and Guitton 1992; Guitton et al. 1990). Thus reduction of burst neuron discharge by an increased OPN inhibition would result in a lower drive to the head motor system and deceleration of the head. In such a scheme, activation of OPNs would affect head trajectory only during gaze shifts because burst neurons are active only for the duration of gaze shifts, and their activity is greatly diminished at the end of gaze shifts (Cullen et al. 1993; Cullen and Guitton 1997). Alternatively, the absence of visible head deceleration effects at the end of gaze shifts may be explained by the natural irregular OPN reactivation being a weaker inhibitory signal than that produced by synchronous electrical activation. Although this hypothesis, in our view, seems unlikely, it remains to be tested.

In monkey, the effect of OPN stimulation on head motion appears highly variable (Coble et al. 1994; Ling et al. 1991; Phillips 1993), and it is assumed that OPNs have no clear influence on the mechanisms controlling head motion. Such a species difference can perhaps be explained by a more prominent coupling between the eye and head motor systems in the cat (Guitton et al. 1990) than in the monkey (Ling et al. 1991; Phillips et al. 1995).

OPNs and control of perisaccadic slow movements

Head-fixed and head-free perisaccadic slow movements have been observed in both human (Bahill et al. 1975; Bahill and Stark 1975; Kapoula et al. 1986; Ron and Berthoz 1991; Ron et al. 1993; Weber and Daroff 1972) and cat (Evinger and Fuchs 1978; Guitton et al. 1984; Missal et al. 1993; Olivier et al. 1993). In the head-free cat, slow gaze movements occasionally link multiple-step gaze saccades evoked either naturally or by SC stimulation (Guitton et al. 1984; Missal et al. 1996; Paré et al. 1994; Roucoux et al. 1980). Guitton et al. (1984) showed that sudden immobilization of the head during intersaccadic slow gaze movements had no effect on the gaze motion, but immediately stopped the compensatory eye movement. Because head immobilization inactivates the vestibuloocular reflex, this observation indicates that slow movements are due to a motor command that is superimposed on the vestibular compensatory signal. Furthermore, Olivier et al. (1993) reported that SC efferent neurons show a prolonged low-frequency discharge during perisaccadic slow movements in the head-fixed cat. The reduced discharge of OPNs that we observed is consistent with the hypothesis that perisaccadic eye movements are generated by the saccadic system to correct small errors in targeting (Missal et al. 1993). Accordingly, brain stem burst neurons would then be more inhibited by OPNs than during saccades, and respond to SC excitation with much lower discharge rates. The saccadic system could therefore use small position error to generate slow corrective gaze movements. In this view, OPNs do not possess only "ON" or "OFF" discharge characteristics: intermediate low rates are permitted and possibly linked to different slow movement velocities.

Gaze-related activity of OPNs

A major finding in our study was that, in active combined eye-head gaze shifts, the end of the pause in activity of OPNs was consistently much better timed to occur with the end of the gaze shift than with the end of the rapid eye movement. This suggests that cat OPNs lie within a gaze control system, and gaze-related neural elements dictate their activity pattern. Further support for this interpretation is provided by the gaze-related pause in activity exhibited by OPNs during both passive and SC-induced gaze movements (see subsequent sections).

Phillips and colleagues recently reported on the OPN activity during gaze shifts in the head-free monkey (Coble et al. 1994; Phillips 1993). In their analysis, they aligned the end of the pause in OPN activity on either the end of the eye saccade, the start of eye counterrotation, or the end of the gaze saccade. Not unlike us, they found that whenever the eye trajectory included a plateau phase in which the eye-in-head velocity was near zero, the OPN pause continued beyond the end of the rapid eye saccade and pause duration correlated with gaze saccade duration. However, in contrast to our results, most gaze saccades often contained no ocular plateau, and the eyes counterrotated near the end of the gaze shift. For these movements as well as for those including a plateau, Phillips (1993) reported that the end of the pause was better aligned on the onset of eye counterrotation than on the end of the gaze shift, which occurred a little later. This view contrasts with our observations, namely, that the eyes can counterrotate to some extent during the OPN pause (see Fig. 2E). It should be emphasized here that eye counterrotation near the end of a gaze shift is entirely compatible with a gaze control mechanism in which the vestibuloocular gain is switched to unity, but not necessarily instantaneously, when gaze motor error approaches zero. The eye counterrotation marks when the system is switching from the saccadic mode (OPNs silent) to the stabilization mode (OPNs and vestibuloocular reflex active). The gaze is stabilized perfectly when the gain of the vestibuloocular reflex has attained unity. Another potential interpretation problem is that some of the temporal differences that Phillips (1993) observed between the start of eye counterrotation and gaze end may have been due to the presence of perisaccadic slow gaze movements, during which monkey OPNs were active. As discussed above, we also found that cat OPNs were active, albeit at a reduced rate, during these slow movements occurring either head-fixed or head-free. However, to avoid the problem related to movement definition, our analysis focused on the more frequent case wherein slow movements did not follow the gaze shifts.

In summary, any purported differences between monkey and cat data may only be caused by how well defined the end of gaze shifts appears. Rapid gaze shifts do not necessarily end abruptly: a short period of slow gaze displacement can terminate a gaze shift caused by the noninstantaneous switching to the gaze stabilization mode. We argue that, taken together, the observations suggest that both cat and monkey OPNs are not controlled by an eye control system, but by a gaze-dependent one. This hypothesis predicts that brain stem burst neurons, targets of the OPNs, should discharge for the entire duration of gaze shifts, even during eye plateaus. This prediction is supported by experimental evidence in both cat and monkey (Cullen et al. 1993; Cullen and Guitton 1997; Ling et al. 1990; Phillips 1993; Tomlinson and Bance 1992).

OPN control during passive gaze shifts

Studies of the vestibular-ocular reflex have used the eye-in-head trajectory as a measure of the output of the system. Our data revealed that, for whole-body rotation, the duration of a rapid eye movement was not necessarily indicative of the duration of the OPN pause, which was best predicted by the gaze shift duration. The results obtained from passive head-on-body rotations in the dark further demonstrate, even more emphatically, that the OPN pause in activity is related to gaze displacement, not to the eye-in-head trajectory. Consequently, we propose that quick phases of nystagmus be defined independently of the eye-in-head trajectory, but rather be considered as the ocular response during which gaze is not stabilized. The latter corresponds to the period during which OPNs are silent and the saccade burst generator is disinhibited.

Our data showed that gaze shifts ended before the passively generated head motion ceased. It is still unclear what mechanisms modulate OPN activity to determine gaze shift amplitude and duration during passive movements, particularly the head-on-body rotations. The signals driving gaze shifts in this latter condition are provided by vestibular and/or neck proprioceptive inputs rather than visual inputs (Barnes 1979; Guitton et al. 1984). In that respect, it is particularly relevant that OPNs receive inputs from the vestibular nucleus (Ito et al. 1984, 1986; Langer and Kaneko 1990) and possibly eye position information from the nucleus prepositus hypoglossi (Ito et al. 1984; Langer and Kaneko 1984, 1990), as well as neck proprioceptive signals from cervical spinal cord also via the nucleus prepositus hypoglossi (McCrea and Baker 1985; Mehler at al. 1960). Models have been proposed for a control of vestibular quick phase onset and termination by circuits located in the pons (Chun and Robinson 1978; Galiana 1991; Schmid and Lardini 1976). In general, these models postulate that quick phases drive the eyes to a position in the orbit that depends on head velocity. This is clearly not the case during passive head-on-body rotations, but nevertheless the structure of these models may give insights into the mechanisms leading to OPN pauses. In Galiana's model, asymmetric bilateral inhibitory projections onto OPNs from vestibular nucleus neurons trigger the pauses in OPN activity, and vestibular quick phases are driven by unilateral activation of the burst generator by vestibular burst-driver neurons (Hardy and Corvisier 1992; Kitama et al. 1995; Ohki et al. 1989). It is assumed that quick phases are stopped when OPN inhibition by inhibitory burst neurons is exceeded by excitation from eye position signals onto OPNs that increases as the quick phase progresses. This scheme suggests that OPNs could display an eye position sensitivity, which has been observed (Cohen and Henn 1972; Paré 1995).

Dissociation between SC-evoked gaze-motor-error signals and OPN pause

Neurophysiological data suggest that, in the cat, SC saccade-related efferent neurons are organized into a retinotopically coded gaze motor map wherein gaze saccade metrics are determined by the spatial location of the neural activity (Munoz and Guitton 1991; Munoz et al. 1991). In addition, a subset of SC fixation-related efferent neurons is located in the SC's rostral end (Munoz and Guitton 1989, 1991; Munoz et al. 1991; Munoz and Wurtz 1993; Peck 1989; Peck and Baro 1997). Both the brain stem burst neurons (Chimoto et al. 1996; Hikosaka and Kawakami 1977) and OPNs (Paré and Guitton 1994b; Raybourn and Keller 1977) receive SC inputs, and the OPNs are preferentially connected with the rostral SC (Büttner-Ennever and Horn 1995; Paré and Guitton 1994b). On the basis of these data, models have been developed wherein the SC controls gaze saccades (Galiana and Guitton 1992; Guitton et al. 1990; Lefèvre and Galiana 1992; Munoz et al. 1991). The motor command encoded by SC output neurons in cat may be the neural correlate of the gaze-motor-error signal postulated by gaze control models to drive neuronal elements composing both the eye and head motor circuits.

In addition to these postulated SC mechanisms, evidence indicates that there appear to be a circuit in the pons capable of controlling vestibularly evoked rapid eye movement onset and termination. First, the SC does not control torsional quick phases of nystagmus (Hepp et al. 1993). Second, horizontal and vertical quick phases are still present after chemical lesions of the SC (Hepp et al. 1993), unilateral ablation of the SC (Flandrin and Jeannerod 1981), or ablation of both the SC and frontal eye fields (Schiller et al. 1980). As an extension to Guitton et al. (1984) and Guitton and Volle (1987), we argue that such quick-phase generating mechanisms, perhaps phylogenetically older, interact with collicular gaze saccade generating mechanisms whenever the head is in motion. If we put it another way, it is assumed that head motion during a gaze shift can generate a command for a quick phase in the direction of the head movement, which interacts with the eye-saccade command associated with the orienting gaze shift. During passive head motion, this pontine circuit can control eye movements independently of the SC signals.

Two of our observations support the preceding argument that the gaze-related pause in activity of OPNs is not caused by the collicular gaze command alone. When the caudal regions of the SC were electrically stimulated, the output signal was presumed to be constant, and determined by the constant stimulation parameters (Paré et al. 1994). Yet, OPN behavior was related to the motor output. In the head-fixed condition, the OPN pauses were modulated on the basis of the difference between initial eye position and the goal position. This is in spite of a caudal SC output that elicited large gaze shifts when the head was free to move. In the head-free condition, the eyes were presumably also driven toward the goal, known to be situated near the plateau position (Paré at al. 1994; Roucoux et al. 1980), but now the pause duration appeared to be modulated by gaze-motor error.

Head perturbations reveal limits to the gaze-motor-error gate

Head perturbation experiments yielded results complementary to those obtained with SC electrical stimulation. When head motion was unexpectedly prevented just after the onset of an active gaze shift, OPN pauses were limited to the duration of the resultant eye saccade (equivalent to a SC-evoked goal-directed saccade). The pause duration did not continue beyond saccade end, even though the eye movement did not null the gaze-motor error. The head and gaze trajectories after head-release suggested that a gaze-motor-error signal still attempted to displace gaze.

These results indicate that OPN pauses are related only to the head-fixed eye saccades or head-free gaze shifts actually performed by the animal, and in contrast to the proposal by many gaze control models (see next section) are not strictly gated by a gaze-motor-error signal. Moreover, the fact that OPNs continue to pause even though the eyes are at their saturation plateau position in the orbits indicates that OPNs are not solely controlled by an eye motor-error signal, but are also influenced by head-related signals, possibly of vestibular origin. However, the mechanisms underlying such interactions between signals in the saccadic and vestibular systems are still speculative.

OPNs and gaze control models

GAZE-MOTOR-ERROR CONTROL. It has been proposed that active eye (head-fixed) and gaze (head-free) saccades are controlled by a feedback loop that produces respectively an eye or gaze-motor-error signal obtained by comparing current and desired positions of the visual axis (Guitton et al. 1990; Guitton and Volle 1987; Laurutis and Robinson 1986; Pélisson et al. 1988, 1989; Robinson 1975; Tomlinson 1990; Zee et al. 1976; reviewed in Guitton 1991, 1992). The existence of such a feedback control system was suggested, for example, by the finding that single-step gaze shifts can be made far beyond the oculomotor range and that their accuracy is maintained despite perturbation to the head trajectory.

In some gaze control models, the OPNs lie within a gaze control circuit: the pause in OPN activity is initiated by a gaze-motor-error signal, and its duration is entirely dictated by gaze-related neural elements (Galiana and Guitton 1992; Guitton et al. 1990; Laurutis and Robinson 1986; Pélisson et al. 1988; Tomlinson 1990). These models may explain the gaze-related discharges of OPNs observed during active movements, but their structure does not address the results obtained when gaze movements are passively generated or evoked by SC stimulation. Moreover, for perturbed gaze shifts, they predict incorrectly that OPNs will be silent until the gaze-motor-error signal is reduced to zero.

EYE-MOTOR-ERROR CONTROL. As an alternative to OPNs being gated by gaze motor-error, it has been proposed that these neurons lie in an eye control circuit and that their gaze-related discharges are manifest because of an operational vestibuloocular reflex. In such a scheme, the burst generator is driven by an eye-motor-error signal (the difference between desired and actual eye positions), and OPNs are kept silent until this quantity is reduced to zero. When the head contributes to the gaze shifts, the eye-motor-error signal driving the eyes toward its goal interacts with the vestibuloocular reflex acting in the opposite direction. Consequently, the eyes may not reach the desired orbital position, and the OPNs will pause for the entire duration of a gaze shift. Also, the OPN pause will resume near eye saccade end when large gaze shifts are requested and the head motion is prevented. A problem with this view is that there is no supporting evidence for the vestibuloocular reflex being active during large gaze shifts. Experiments in which the head motion was interrupted during ongoing gaze shifts showed that the vestibuloocular reflex can be "OFF" during gaze shifts (Fuller et al. 1983; Laurutis and Robinson 1986; Tomlison and Bahra 1986; Guitton and Volle 1987; Pélisson et al. 1988). In addition, in the case of vestibularly driven gaze shifts, the occurrence of eye plateaus cannot be explained by a simple interaction between the vestibular quick and slow phases (Jürgens et al. 1981a,b).

The model proposed by Phillips et al. (1995) places OPNs in an eye-motor-error control loop and accounts for the inactivation of the vestibuloocular reflex during gaze shifts. However, OPNs are aware of neither actual eye/gaze position nor eye/gaze displacement. This structure does not predict that the end of OPN pauses, during eye plateaus, is closely linked to the end of gaze shifts. Last, this model addresses neither the role of the SC, nor how vestibular quick phases are dealt with during active and passive gaze shifts. In the model of Guitton and Volle (1987), the OPN pause duration is controlled by gaze motor-error during gaze shifts and by eye motor-error during vestibular nystagmus. Although it also does not consider the SC, an advantage of this structure is that it considers the problem of how OPNs and the burst generator become liable to vestibular signals created by head motion during active and passive gaze shifts, a phenomenon particularly relevant to our experimental observations. None of the models addresses the important differences in eye trajectories between passive whole-body and head-on-body rotations.


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FIG. 13. Summary of the inputs acting onto OPNs during the execution of combined eye-head gaze shifts. OPNs inhibit the burst generator(Büttner-Ennever and Büttner 1978; Curthoys et al. 1984; Furuya and Markham 1982; Horn et al. 1994; Langer and Kaneko 1983; Nakao et al. 1980, 1988; Ohgaki et al. 1987, 1989; Strassman et al. 1987), including the inhibitory burst neurons, which in turn inhibit the OPNs during saccades (Paré and Guitton 1994a; Scudder et al. 1988). The SC influences the discharges of OPNs mainly through the excitatory projection of SC fixation neurons (Paré and Guitton 1994b). In the quick-phase generator circuit, bilateral head-velocity signals from the vestibular nucleus (Ito et al. 1986) and an unilateral eye position signal from the prepositus hypoglossi nucleus (Ito et al. 1984; Langer and Kaneko 1984, 1990) are assumed to initiate and end the pause in activity of OPNs. Finally, OPNs receive a bias input that maintains their tonic discharges in the absence of significant other inputs (Scudder 1988).

A major problem with any hypothesis that OPNs function within an eye-motor-error control loop is that accumulating evidence indicates that the saccade burst generator itself, with which OPNs are intimately linked, carries gaze-related signals. Indeed, during gaze shifts the discharge rate of inhibitory burst neurons in both cat and monkey is a function of the sum of both eye and head velocity (Cullen at al. 1993; Cullen and Guitton 1997).

Conclusions

The major finding of this paper is that, in the head-free cat, the duration of OPN pauses is tightly linked to the duration of saccadic gaze shifts but is not controlled uniquely by a gaze-motor-error signal. No single existing model describing the control of combined eye-head gaze shifts can account for the present observations, which obviously point to the need for developing more unified models.

To emphasize the diversity of signals that have to be dealt with, Fig. 13 illustrates the combination of inputs acting on OPNs during the execution of combined eye-head gaze shifts. As discussed above, OPNs inhibit the burst generator including the inhibitory burst neurons, which in turn provide a feedback inhibitory input signal. OPNs are thought to be excited by SC fixation neurons and thus under the control of a collicular gaze-motor-error signal. In the quick-phase generator circuit, two signals appear to be important controlling parameters: OPNs are excited by unilateral eye position signals from the prepositus hypoglossi nucleus and inhibited by bilateral head-velocity signals from the vestibular nucleus. Finally, OPNs have a bias input that assures a tonic discharge even when other inputs are silent.

In closing, we emphasize that there exist both SC and pontine mechanisms for triggering and stopping saccadic eye movements, and, in natural orienting gaze shifts involving coordinated eye-head motion, these can operate together. The various input signals onto OPNs make these brain stem neurons a component of a complex system whose controlling mechanism is multifaceted.

    ACKNOWLEDGEMENTS

  We gratefully acknowledge Dr. Marc Crommelinck who participated in some experiments. The interactive graphics program was provided courtesy of Dr. R. M. Douglas, Ophthalmology Department, University of British Columbia, Canada.

  This work was supported by the Medical Research Council of Canada (MRC), Le fonds de la Recherche en Santé du Québec, and National Eye Institute Grant EY-08216. During this project M. Paré held a MRC studentship.

    FOOTNOTES

  Present address and address for reprint requests: M. Paré, Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.

  Received 7 August 1997; accepted in final form 5 March 1998.

    REFERENCES
Abstract
Introduction
Methods
Results
Discussion
References

0022-3077/98 $5.00 Copyright ©1998 The American Physiological Society