Comparison of saccades perturbed by stimulation of the rostral superior colliculus, the caudal superior colliculus, and the omnipause neuron region

Over the past decade, considerable research efforts have been focused on the role of the rostral superior colliculus (SC) in control of saccades. The most recent theory separates the deeper intermediate layers of the SC into two functional regions: the rostral pole of these layers constitutes a fixation zone and the caudal region comprises the saccade zone. Sustained activity of fixation neurons in the fixation zone is argued to maintain fixation and help prevent saccade generation by exciting the omnipause neurons (OPNs) in the brain stem. This hypothesis is in contrast to the traditional view that the SC contains a topographic representation of the saccade motor map on which the rostral pole of the SC encodes signals for generating small saccades (<2 degrees ) instead of preventing them. There is therefore an unresolved controversy about the specific role on the most rostral region of the SC, and we reexamined its functional contribution by quantifying and comparing spatial and temporal trajectories of 30 degrees saccades perturbed by electrical stimulation of the rostral pole and more caudal regions in the SC and of the OPN region. If the rostral pole serves to preserve fixation, then saccades perturbed by stimulation should closely resemble interrupted saccades produced by stimulation of the OPN region. If it also contributes to saccade generation, then the disrupted movements would better compare with redirected saccades observed after stimulation of the caudal SC. Our experiments revealed two significant findings: 1) the locus of stimulation was the primary factor determining the perturbation effect. If the directions of the target-directed saccade and stimulation-evoked saccade were aligned and if the stimulation was delivered within approximately the rostral 2 mm (<10 degrees amplitude) of SC, the ongoing saccade stopped in midflight but then resumed after stimulation end to reach the original visually specified goal with close to normal accuracy. When stimulation was applied at more caudal sites, the ongoing saccade directly reached the target location without stopping at an intermediate position. If the directions differed considerably, both initial and resumed components were typically observed for all stimulation sites. 2) A quantitative analysis of the saccades perturbed from the fixation zone showed significant deviations from their control spatial trajectories. Thus they resembled redirected saccades induced by caudal SC stimulation and differed significantly from interrupted saccades produced by OPN stimulation. The amplitude of the initial saccade, latency of perturbation, and spatial redirection were greatest for the most caudal sites and decreased gradually for rostral sites. For stimulation sites within the rostral pole of SC, the measures formed a smooth continuation of the trends observed in the saccade zone. As these results argue for the saccade zone concept, we offer reinterpretations of the data used to support the fixation zone model. However, we also discuss scenarios that do not allow an outright rejection of the fixation zone hypothesis.     

In multiple-step gaze shifts: omnipause (OPNs) and collicular fixation neurons encode gaze position error; OPNs gate saccades

The superior colliculus (SC), via its projections to the pons, is a critical structure for driving rapid orienting movements of the visual axis, called gaze saccades, composed of coordinated eye-head movements. The SC contains a motor map that encodes small saccade vectors rostrally and large ones caudally. A zone in the rostral pole may have a different function. It contains superior colliculus fixation neurons (SCFNs) with probable projections to omnipause neurons (OPNs) of the pons. SCFNs and OPNs discharge tonically during visual fixation and pause during single-step gaze saccades. The OPN tonic discharge inhibits saccades and its cessation (pause) permits saccade generation. We have proposed that SCFNs control the OPN discharge. We compared the discharges of SCFNs and OPNs recorded while cats oriented horizontally, to the left and right, in the dark to a remembered target. Cats used multiple-step gaze shifts composed of a series of small gaze saccades, of variable amplitude and number, separated by periods of variable duration (plateaus) in which gaze was immobile or moving at low velocity (<25 degrees /s). Just after contralaterally (ipsilaterally) presented targets, the firing frequency of SCFNs decreased to almost zero (remained constant at background). As multiple-step gaze shifts progressed in either direction in the dark, these activity levels prevailed until the distance between gaze and target [gaze position error (GPE)] reached approximately 16 degrees. At this point, firing frequency gradually increased, without saccade-related pauses, until a maximum was reached when gaze arrived on target location (GPE = 0 degrees). SCFN firing frequency encoded GPE; activity was not correlated to characteristics or occurrence of gaze saccades. By comparison, after target presentation to left or right, OPN activity remained steady at pretarget background until first gaze saccade onset, during which activity paused. During the first plateau, activity resumed at a level lower than background and continued at this level during subsequent plateaus until GPE approximately 8 degrees was reached. As GPE decreased further, tonic activity during plateaus gradually increased until a maximum (greater than background) was reached when gaze was on goal (GPE = 0 degrees). OPNs, like SCFNs, encoded GPE, but they paused during every gaze saccade, thereby revealing, unlike for SCFNs, strong coupling to motor events. The firing frequency increase in SCFNs as GPE decreased, irrespective of trajectory characteristics, implies these cells get feedback on GPE, which they may communicate to OPNs. We hypothesize that at the end of a gaze-step sequence, impulses from SCFNs onto OPNs may suppress further movements away from the target.     

Glycinergic inputs cause the pause of pontine omnipause neurons during saccades

Pontine omnipause neurons (OPNs) are inhibitory neurons projecting to saccade-related premotor burst neurons. OPNs exhibit sustained discharge during fixations and cease firing before and during saccades. The pause in OPN discharge releases the burst neurons from tonic inhibition, resulting in generation of saccadic eye movements. OPNs are thought to receive two major inhibitory inputs during saccades: an early component that determines the pause onset and a late component that controls the pause duration. Although there is evidence that numerous glycinergic and GABAergic terminals contact OPNs, their physiological roles remain unclear. To reveal functions of glycinergic and GABAergic inputs, we investigated effects of iontophoretic application of strychnine, a glycine receptor antagonist, and bicuculline, a GABAA receptor antagonist, on discharge patterns of OPNs in alert cats. Application of strychnine reduced the ratio of pause duration to saccade duration. Analysis of the timing of pause relative to saccades showed that pause onset was delayed and pause end was advanced. These effects were observed for saccades in all directions. Application of bicuculline, in contrast, had no effect on the OPN pause duration or timing. Both strychnine and bicuculline increased tonic firing rate during intersaccadic intervals. These results suggest that glycinergic, but not GABAergic, afferents convey inhibitory signals that determine the onset as well as duration of pause in OPN activity during saccades.     

Saccades and multisaccadic gaze shifts are gated by different pontine omnipause neurons in head-fixed cats

 Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts. Received: 20 January 1998 / Accepted: 22 October 1998     

Disynaptic inhibition of omnipause neurons following electrical stimulation of the superior colliculus in alert cats

We investigated the synaptic organization responsible for the inhibition of omnipause neurons (OPNs) following stimulation of the superior colliculus (SC) in alert cats. Stimulation electrodes were implanted bilaterally in the rostral and caudal SC where a short-pulse train induced small and large saccades, respectively. Effects of single-pulse stimulation on OPNs were examined with intracellular and extracellular recordings. In contrast to monosynaptic excitatory postsynaptic potentials, which were induced by rostral SC stimulation, inhibitory postsynaptic potentials were induced with disynaptic latencies (1.3--1.9 ms) from both the rostral and caudal SC in most OPNs. Analysis of a larger extracellular sample complemented intracellular observations. Monosynaptic activation of OPNs was elicited more frequently from rostral sites than from caudal sites, whereas spike suppression with disynaptic latencies was induced by caudal as well as rostral stimulation with similar frequencies. The results imply that disynaptic inhibition is produced by activation of SC cells that are distributed over wide regions related to saccades of different sizes. We suggest that signals from these neurons initiate a saccadic pause of OPNs through single inhibitory interneurons.     

Action of the brain stem saccade generator during horizontal gaze shifts. I. Discharge patterns of omnidirectional pause neurons

Omnidirectional pause neurons (OPNs) pause for the duration of a saccade in all directions because they are part of the neural mechanism that controls saccade duration. In the natural situation, however, large saccades are accompanied by head movements to produce rapid gaze shifts. To determine whether OPNs are part of the mechanism that controls the whole gaze shift rather than the eye saccade alone, we monitored the activity of 44 OPNs that paused for rightward and leftward gaze shifts but otherwise discharged at relatively constant average rates. Pause duration was well correlated with the duration of either eye or gaze movement but poorly correlated with the duration of head movement. The time of pause onset was aligned tightly with the onset of either eye or gaze movement but only loosely aligned with the onset of head movement. These data suggest that the OPN pause does not encode the duration of head movement. Further, the end of the OPN pause was often better aligned with the end of the eye movement than with the end of the gaze movement for individual gaze shifts. For most gaze shifts, the eye component ended with an immediate counterrotation owing to the vestibuloocular reflex (VOR), and gaze ended at variable times thereafter. In those gaze shifts where eye counterrotation was delayed, the end of the pause also was delayed. Taken together, these data suggest that the end of the pause influences the onset of eye counterrotation, not the end of the gaze shift. We suggest that OPN neurons act to control only that portion of the gaze movement that is commanded by the eye burst generator. This command is expressed by driving the saccadic eye movement directly and also by suppressing VOR eye counterrotation. Because gaze end is less well correlated with pause end and often occurs well after counterrotation onset, we conclude that elements of the burst generator typically are not active till gaze end, and that gaze end is determined by another mechanism independent of the OPNs.     

Minimal synaptic delay in the saccadic output pathway of the superior colliculus studied in awake monkey

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50–100 A, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9±1.0 ms (SD; ipsilateral eye) and 7.8±0.9 ms (SD; contralateral eye) for SC stimulation; 4.8±0.5 ms (SD; ipsilateral eye) and 5.1±0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6±0.4 ms (SD; ipsilateral eye) and 5.2±0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.     

Pontine omnipause activity during conjugate and disconjugate eye movements in macaques

Previous reports have shown that saccades executed during vergence eye movements are often slower and longer than conjugate saccades. Lesions in the nucleus raphe interpositus, where pontine omnipause neurons (OPNs) are located, were also shown to result in slower and longer saccades. If vergence transiently suppresses the activity of the OPNs just before a saccade, then reduced presaccadic activity might mimic the behavioral effects of a lesion. To test this hypothesis, 64 OPNs were recorded from 7 alert rhesus monkeys during smooth vergence and saccades with and without vergence. The firing rate of many OPNs was modulated by static vergence angle but not by version and showed transient changes during slow vergence without saccades. This modulation was smooth, and not the abrupt pause seen for saccades, indicating that OPNs do not act as gates for vergence commands. We confirmed that saccades made during both convergence and divergence are significantly slower and longer than conjugate saccades. OPNs paused for all saccades, and the pause lead (interval between pause onset and saccadic onset) was significantly longer for saccades with convergence, in agreement with our hypothesis. Contrary to our hypothesis, pause lead was not longer for saccades with divergence, even though these saccades were slowed as much as those occurring during convergence. Furthermore, there was no significant correlation, on a trial-by-trial basis, between pause lead and saccadic slowing. These results suggest that it is unlikely that presaccadic slowing of OPNs is responsible for the slower saccades seen during vergence movements.     

Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys

1. The discharge of 255 neurons in the fastigial nuclei of three trained macaque monkeys was investigated during visually guided saccades. Responses of these neurons were examined also during horizontal head rotation and during microstimulation of the oculomotor vermis (lobules VIc and VII). 2. One hundred and two units were characterized by bursts of firing in response to visually guided saccades. Ninety-eight of these (96.1%) were located within the anatomic confines of the fastigial oculomotor region (FOR), on the basis of reconstruction of recording sites. During contralateral saccades, these neurons showed bursts that preceded the onset of saccades (presaccadic burst), whereas, during ipsilateral saccades, they showed bursts associated with the end of saccades (late saccadic burst). They were hence named saccadic burst neurons. Sixty-one saccadic burst neurons (62.2%) were inhibited during microstimulation of the oculomotor vermis with currents less than 10 microA. 3. All saccadic burst neurons were spontaneously active, and the resting firing rate varied considerably among units, ranging from 10 to 50 imp/s. The tonic levels of activity did not correlate significantly with eye position. 4. The presaccadic burst started 18.5 +/- 4.7 (SD) ms (n = 45) before the onset of saccades in the optimal direction (the direction associated with the maximum values of burst lead time, number of spikes per burst, and burst duration). Optimal directions covered the entire contralateral hemifield, although there was a slightly higher incidence in both horizontal and upper-oblique directions in the present sample. The duration of the presaccadic burst was highly correlated with the duration of saccade (0.85 less than or equal to r less than or equal to 0.97). 5. The late saccadic burst was most robust in the direction opposite to the optimal in each unit (the nonoptimal direction). Its onset preceded the completion of ipsilateral saccade by 30.4 +/- 5.9 ms. The lead time to the end of saccade was consistent among different units and was constant also for saccades of various sizes. Thus the late saccadic burst started even before the saccade onset when the saccade duration was less than 30 ms. Unlike the presaccadic burst, its duration was not related to the duration of saccade. 6. Discharge rates of saccadic burst neurons were correlated neither to eye positions during fixation nor to the initial eye positions before saccades. 7. Eye-position units and horizontal head-velocity units were located rostral to the FOR.(ABSTRACT TRUNCATED AT 400 WORDS)     

Role of the rostral superior colliculus in active visual fixation and execution of express saccades.

1. In the rostral pole of the monkey superior colliculus (SC) a subset of neurons (fixation cells) discharge tonically when a monkey actively fixates a target spot and pause during the execution of saccadic eye movements. 2. To test whether these fixation cells are necessary for the control of visual fixation and saccade suppression, we artificially inhibited them with a local injection of muscimol, an agonist of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). After injection of muscimol into the rostral pole of one SC, the monkey was less able to suppress the initiation of saccades. Many unwanted visually guided saccades were initiated less than 100 ms after onset of a peripheral visual stimulus and therefore fell into the range of express saccades. 3. We propose that fixation cells in the rostral SC form part of a fixation system that facilitates active visual fixation and suppresses the initiation of unwanted saccadic eye movements. Express saccades can only occur when activity in this fixation system is reduced.     

Competition between saccade goals in the superior colliculus produces saccade curvature

When saccadic eye movements are made in a search task that requires selecting a target from distractors, the movements show greater curvature in their trajectories than similar saccades made to single stimuli. To test the hypothesis that this increase in curvature arises from competitive interactions between saccade goals occurring near the time of movement onset, we performed single-unit recording and microstimulation experiments in the superior colliculus (SC). We found that saccades that ended near the target but curved toward a distractor were accompanied by increased presaccadic activity of SC neurons coding the distractor site. This increased activity occurred approximately 30 ms before saccade onset and was abruptly quenched on saccade initiation. The magnitude of increased activity at the distractor site was correlated with the amount of curvature toward the distractor. In contrast, neurons coding the target location did not show any significant difference in discharge for curved versus straight saccades. To determine whether this pattern of SC discharge is causally related to saccade curvature, we performed a second series of experiments using electrical microstimulation. Monkeys made saccades to single visual stimuli presented without distractors, and we stimulated sites in the SC that would have corresponded to distractor sites in the search task. The stimulation was subthreshold for evoking saccades, but when its temporal structure mimicked the activity recorded for curved saccades in search, the subsequent saccades to the visual target showed curvature toward the location coded by the stimulation site. The effect was larger for higher stimulation frequencies and when the stimulation site was in the same colliculus as the representation of the visual target. These results support the hypothesis that the increased saccade curvature observed in search arises from rivalry between target and distractor goals and are consistent with the idea that the SC is involved in the competitive neural interactions underlying saccade target selection.     

Saccade-related inhibitory input to pontine omnipause neurons: an intracellular study in alert cats.

Omnipause neurons (OPNs) are midline pontine neurons that are thought to control a number of oculomotor behaviors, especially saccades. Intracellular recordings were made from OPNs in alert cats to elucidate saccade-associated postsynaptic events in OPNs and thereby determine what patterns of afferent discharge impinge on OPNs to cause their saccadic inhibition. The membrane potential of impaled OPNs exhibited steep hyperpolarization before each saccade that lasted for the whole period of the saccade. The hyperpolarization was reversed to depolarization by intracellular injection of Cl- ions, indicating it consisted of temporal summation of inhibitory postsynaptic potentials (IPSPs). The duration of the saccade-related hyperpolarization was almost equal to the duration of the concurrent saccades. The time course of the hyperpolarization was similar to that of the radial eye velocity except for the initial phase. During the falling phase of eye velocity, the correlation between the instantaneous amplitude of hyperpolarization and the instantaneous eye velocity was highly significant. The amplitude of hyperpolarization at the eye velocity peak was correlated significantly with the peak eye velocity. The time integral of the hyperpolarization was correlated with the radial amplitude of saccades. The initial phase disparity between the hyperpolarization and eye velocity was due to the relative constancy of peak time (approximately 20 ms) of the initial steep hyperpolarization regardless of the later potential profile that covaried with the eye velocity. The initial steep hyperpolarization led the beginning of saccades by 15.9 +/- 3.8 (SD) ms, which is longer than the lead time for medium-lead burst neurons. These results demonstrate that the pause of activity in OPNs is caused by IPSPs initiated by an abrupt, intense input and maintained, for the whole duration of the saccade, by afferents conveying eye velocity signals. We suggest that the initial sudden inhibition originates from central structures such as the superior colliculus and frontal eye fields and that the eye velocity-related inhibition originates from the burst generator in the brain stem.     

Discharge patterns of neurons in the rostral superior colliculus of cat: activity related to fixation of visual and auditory targets

Neurons in the rostral superior colliculus (SC) of alert cats exhibit quasi-sustained discharge patterns related to the fixation of visual targets. Because some SC neurons also respond to auditory stimuli, we investigated whether there is a population of neurons in the rostral SC which is active in relation to fixation of both auditory and visual targets. We identified cells which were active with visual fixation and which continued to discharge if the fixation stimulus was briefly extinguished. The population of neurons exhibited similar discharge characteristics when the fixation stimulus was auditory. Few neurons were significantly more active during fixation of visual targets than during fixation of auditory targets. Most fixation neurons showed a diminished discharge rate during spontaneous (self-generated) saccadic eye movements away from a visual fixation stimulus, regardless of the direction of the saccade. this diminished discharge rate (or pause) typically began, on average, 12.2 ms before saccade onset and the duration of the pause was Ionger than the duration of the saccade. These observations are consistent with the hypothesis that increased discharge of these neurons is related to active fixation and that reductions in their activity are important for the generation of saccades. However, the lack of a precise relationship between pause duration and saccade duration implies that these neurons would be unlikely to project directly to the saccadic burst generator. The mean interval from the beginning of the pauses of fixation neurons to be beginning of the saccades away from fixation targets is also shorter than has been found in brainstem omnipause neurons. By analogy with the concept of a receptive field, agaze position error field depicts the range of gaze position error for which a cell is active. Although fixation neurons appear to encode the magnitude and direction of the error between visual targets and the visual axis, visual error fields at the end of fixating eye movements were significantly larger than those at stimulus onset. For auditory stimuli, this difference was not significant. These observations are compatible with a number of recent experiments indicating that neural signals of eye position are damped or delayed with respect to current eye position.     

Activity in deep intermediate layer collicular neurons during interrupted saccades

The activity of neurons located in the deep intermediate and adjacent deep layers (hereafter called just deep intermediate layer neurons) of the superior colliculus (SC) in monkeys was recorded during saccades interrupted by electrical stimulation of the brainstem omnipause neuron (OPN) region. The goal of the experiment was to determine if these neurons maintained their discharge during the saccadic interruption, and thus, could potentially provide a memory trace for the intended movement which ends accurately on target in spite of the perturbation. The collicular neurons recorded in the present study were located in the rostral three-fifths of the colliculus. Most of these cells tended to show considerable presaccadic activity during a delayed saccade paradigm, and, therefore, probably overlap with the population of SC cells called buildup neurons or prelude bursters in previous studies. The effect of electrical stimulation in the OPN region (which interrupted ongoing saccades) on the discharge of these neurons was measured by computing the percentage reduction in a cell's activity compared to that present during non-interrupted saccades. During saccade interruption about 70% of deep intermediate layer neurons experienced a major reduction (30% or greater) in their activity, but discharge recovered quickly after the termination of the stimulation as the eyes resumed their movement to finish the saccade on the target. Therefore, the pattern of activity recorded in most of the deep intermediate layer neurons during interrupted saccades qualitatively resembled that previously reported for the saccade-related burst neurons which tend to be located more dorsally in the intermediate layer. In contrast, some of our cells (30%) showed little or no perturbation in their activity caused by the saccade interrupting stimulation. Because all the more dorsally located burst neurons and the majority of our deep intermediate layer neurons show a total or major suppression in their discharge during interrupted saccades, it seems unlikely that the colliculus by itself could maintain an accurate memory of the desired saccadic goal or the remaining dynamic motor error required to account for the accuracy of the resumed movement which occurs following the interruption. However, it remains possible that the smaller proportion of our neurons whose activity was not perturbed during interrupted movements could play a role in the mechanisms underlying saccade accuracy in the interrupted saccade paradigm. Interrupted saccades have longer durations than normal saccades to the same target. Therefore, we investigated whether the discharge of our deeper collicular cells was also necessarily prolonged during interrupted saccades, and, if so, how the prolongation compared to the prolongation of the saccade. Sixty percent of our sample neurons showed a prolongation in discharge that was approximately the same as the prolongation in saccade duration (difference < 15 ms in magnitude). The, observation that temporal discharge in our neurons was perturbed to roughly match saccadic temporal perturbation suggests that dynamic feedback about ongoing saccadic motion is provided to the colliculus, but does not necessarily imply that this structure is the site responsible for the computation of dynamic motor error.     

Common inhibitory mechanism for saccades and smooth-pursuit eye movements

The premotor pathways subserving saccades and smooth-pursuit eye movements are usually thought to be different. Indeed, saccade and smooth-pursuit eye movements have different dynamics and functions. In particular, a group of midline cells in the pons called omnipause neurons (OPNs) are considered to be part of the saccadic system only. It has been established that OPNs keep premotor neurons for saccades under constant inhibition during fixation periods. Saccades occur only when the activity of OPNs has completely stopped or paused. Accordingly, electrical stimulation in the region of OPNs inhibits premotor neurons and interrupts saccades. The premotor relay for smooth pursuit is thought to be organized differently and omnipause neurons are not supposed to be involved in smooth-pursuit eye movements. To investigate this supposition, OPNs were recorded during saccades and during smooth pursuit in the monkey (Macaca mulatta). Unexpectedly, we found that neuronal activity of OPNs decreased during smooth pursuit. The resulting activity reduction reached statistical significance in approximately 50% of OPNs recorded during pursuit of a target moving at 40 degrees /s. On average, activity was reduced by 34% but never completely stopped or paused. The onset of activity reduction coincided with the onset of smooth pursuit. The duration of activity reduction was correlated with pursuit duration and its intensity was correlated with eye velocity. Activity reduction was observed even in the absence of catch-up saccades that frequently occur during pursuit. Electrical microstimulation in the OPNs' area induced a strong deceleration of the eye during smooth pursuit. These results suggest that OPNs form an inhibitory mechanism that could control the time course of smooth pursuit. This inhibitory mechanism is part of the fixation system and is probably needed to avoid reflexive eye movements toward targets that are not purposefully selected. This study shows that saccades and smooth pursuit, although they are different kinds of eye movements, are controlled by the same inhibitory system.     

Convergence eye movements evoked by microstimulation of the rostral superior colliculus in the cat

Results of our previous studies suggest that the circumscribed area in the rostral superior colliculus (SC) of the cat is involved in the control of accommodation. Accommodation is closely linked with vergence eye movements. In this study, we investigated whether or not vergence eye movements are evoked by microstimulation of the rostral SC in the cat. In addition, we studied the effect of chemical inhibition of the rostral SC on visually guided vergence eye movements. This study was conducted on three cats, weighing 2.5-3.5 kg. The animals were trained to carry out visually guided saccade and convergence tasks. Eye movements were measured using search coils placed on both eyes. We recorded eye movements evoked by microstimulation of the rostral SC in the alert cats. Muscimol was injected into the rostral SC, and the effect of SC inactivation on visually guided vergence eye movements was investigated. Convergence eye movements were evoked by low-current stimulation (< 30 microA) of a circumscribed area in the intermediate layers of the rostral SC on one side. Spontaneous saccades were interrupted by the stimulation of the low-threshold area for evoking convergence. Visually guided convergence eye movements were severely diminished by the injection of muscimol into the low-threshold area for evoking convergence of the SC. The rostral SC is related to the control of vergence eye movements as well as accommodation. The rostral SC may be involved in the functional linkage between accommodation, convergence and visual fixation.     

Commissural excitation and inhibition by the superior colliculus in tectoreticular neurons projecting to omnipause neuron and inhibitory burst neuron regions

Previous electrophysiological studies have shown that the commissural connections between the two superior colliculi are mainly inhibitory with fewer excitatory connections. However, the functional roles of the commissural connections are not well understood, so we sought to clarify the physiology of tectal commissural excitation and inhibition of tectoreticular neurons (TRNs) in the "fixation " and "saccade " zones of the superior colliculus (SC). By recording intracellular potentials, we identified TRNs by their antidromic responses to stimulation of the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed the effects of stimulation of the contralateral SC on these TRNs in anesthetized cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and received mono- or disynaptic inhibition from the entire rostrocaudal extent of the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or IBN region and received monosynaptic excitation from the most rostral level of the contralateral SC, and mono- or disynaptic inhibition from its entire rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN-projecting TRNs also projected to Forel's field H (vertical gaze center), suggesting that they were most likely saccade neurons related to vertical saccades. In contrast, TRNs projecting only to the OPN region were most likely fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple axon branches throughout the rostrocaudal extent of the contralateral SC, whereas excitatory commissural neurons, most of which were rostral TRNs, distributed terminals to a discrete region in the rostral SC.     

Saccade-vergence interactions in macaques. I. Test of the omnipause Multiply Model

Horizontal vergence eye movements are movements in opposite directions used to change fixation between far and near targets. The occurrence of a saccade during vergence causes vergence velocity to be transiently enhanced. The goal of this study was to test in the monkey the previously described Multiply Model (Zee et al. 1992) that holds that, in humans, the speeding of vergence during a saccade may be the result of the disinhibition of a subgroup of vergence-related neurons by the saccadic omnipause neurons (OPNs). In agreement with the Multiply Model: 1) the onset of the enhancement was closely related to saccadic onset, and thus linked to the onset of the OPN pause; 2) the magnitude of the vergence velocity enhancement was strongly dependent on saccade-vergence timing. Contrary to the Multiply Model: 1) the peak of the vergence velocity enhancement was dependent on saccadic peak velocity; 2) the dependency on saccadic peak velocity was not the indirect result of a dependency on saccadic duration and therefore on the duration of the OPN pause; 3) the decline of the vergence enhancement, identified by the time of the peak of the enhancement velocity, occurred too early to be linked to the end of the OPN pause; 4) vergence enhancement had a saccadic-like peak-velocity/size main sequence. Overall, the evidence is incompatible with the OPN Multiply hypothesis of vergence enhancement. Alternative models are described in an accompanying paper.     

Direct inhibitory projection of pontine omnipause neurons to burst neurons in the Forel's field H controlling vertical eye movement-related motoneurons in the cat

Summary This study examines the nature of the efferent projection of omnipause neurons (OPNs) in the midline pontine tegmentum to medium-lead burst neurons (BNs) in the Forel's field H (FFH), both of which exhibit activities related to vertical eye movements, using chronically prepared alert cats. Antidromic spikes of the BNs evoked by oculomotor nucleus stimulation were suppressed by shortly preceding (less than 5 ms) microstimulation within the OPN area including actual recording sites of OPNs. Many OPNs were antidromically activated by microstimulation at recording sites of the BNs. Furthermore, systematic tracking in and around the FFH with the stimulating microelectrode substantiated that the OPNs issued axonal branches within the BN area. These results suggest direct inhibitory projection of OPNs to the BNs.     

Temporal interactions of air-puff-evoked blinks and saccadic eye movements: insights into motor preparation

Following the initial, sensory response to stimulus presentation, activity in many saccade-related burst neurons along the oculomotor neuraxis is observed as a gradually increasing low-frequency discharge hypothesized to encode both timing and metrics of the impending eye movement. When the activity reaches an activation threshold level, these cells discharge a high-frequency burst, inhibit the pontine omnipause neurons (OPNs) and trigger a high-velocity eye movement known as saccade. We tested whether early cessation of OPN activity, prior to when it ordinarily pauses, acts to effectively lower the threshold and prematurely trigger a movement of modified metrics and/or dynamics. Relying on the observation that OPN discharge ceases during not only saccades but also blinks, air-puffs were delivered to one eye to evoke blinks as monkeys performed standard oculomotor tasks. We observed a linear relationship between blink and saccade onsets when the blink occurred shortly after the cue to initiate the movement but before the average reaction time. Blinks that preceded and overlapped with the cue increased saccade latency. Blinks evoked during the overlap period of the delayed saccade task, when target location is known but a saccade cannot be initiated for correct performance, failed to trigger saccades prematurely. Furthermore, when saccade and blink execution coincided temporally, the peak velocity of the eye movement was attenuated, and its initial velocity was correlated with its latency. Despite the perturbations, saccade accuracy was maintained across all blink times and task types. Collectively, these results support the notion that temporal features of the low-frequency activity encode aspects of a premotor command and imply that inhibition of OPNs alone is not sufficient to trigger saccades.