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  • Pontine Omnipause Activity During Conjugate and Disconjugate Eye Movements in Macaques

    C. Busettini and L. E. Mays Department of Physiological Optics and Vision Science Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294

    Submitted 25 September 2002; accepted in final form 16 August 2003

    Busettini, C. and L. E. Mays. Pontine omnipause activity during conjugate and disconjugate eye movements in macaques. J Neuro- physiol 90: 3838–3853, 2003. First published August 20, 2003; 10.1152/jn.00858.2002. 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 sac- cadic 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.

    I N T R O D U C T I O N

    Pontine omnipause neurons (OPNs), located in the nucleus raphe interpositus (Büttner-Ennever et al. 1988) are a critical component of the primate saccadic eye movement system. These neurons fire tonically in alert animals during fixation and pause just before and during saccades or quick phase eye movements of any size and direction (Everling et al. 1998; Raybourn and Keller 1977). OPNs must be silent for a saccade or quick phase to occur or to continue. Electrical microstimu- lation of the raphe interpositus delays the execution of a saccade and interrupts a saccade already started (Becker et al. 1981; Keller 1977; Keller et al. 1996; King and Fuchs 1977). OPNs exert this effect on saccades because they strongly inhibit pontine and midbrain saccadic medium lead burst

    (MLB) neurons. These burst neurons provide motoneurons with the eye velocity signals required for saccades.

    The relationship between OPN activity and conjugate (i.e., without changes in depth) saccades of different sizes and durations has been investigated in cats (Evinger 1982; Paré and Guitton 1998) and in monkeys (Fuchs 1991). For the monkey, there is general agreement that there is a good correlation between saccadic start and pause start. OPNs resume firing around the saccadic end (Everling et al. 1998; Fuchs 1991), although the timing correlation with the end of the saccade is not as strong as that between pause onset and saccadic onset and varies among cells.

    The observation that OPNs must pause for saccades to occur, together with the finding that they receive inputs from saccadic-related brain areas, places them in a crucial role in models of the saccadic system. Surprisingly, damage to OPNs does not cause the devastating effects such as opsoclonus that might be expected by the loss of burst neuron inhibition, as an early model (Zee and Robinson 1979) and some clinical studies (Ashe et al. 1991; Averbuch-Heller and Remler 1996) have suggested. The most evident effect of experimental damage to OPNs is slower but otherwise normal saccades (Kaneko 1996; Soetedjo et al. 2002). Although the precise mechanism is unknown, this result has been successfully simulated by the reduction of OPN activity within contemporary models of the saccadic system (Moschovakis 1994; Scudder 1988). In their models, the execution of a saccade is preceded by a gradual charging of the long lead burst neurons (LLBNs). At saccadic onset the LLBN signal starts to decrease. If a weakened OPN inhibition causes a premature release of the MLB cells during the integrating phase and therefore a premature start of the saccade, the local circuits will start to inhibit the LLBN inte- gration before it reaches its optimal value. Consequently, the peak firing rate of the MLB cells will be lower. Behaviorally, this translates into a slower and longer saccade.

    Several studies (Collewijn et al. 1995; Erkelens et al. 1989; van Leeuwen et al. 1998) have noted that horizontal saccades are often slowed when combined with vergence eye move- ments. Such mixed saccadic-vergence movements are typical of refixations in depth. We have noted that some OPNs show significant decreases in firing rate during vergence movements in the absence of saccades (Busettini and Mays 1999). Addi-

    Address for reprint requests and other correspondence: C. Busettini, Vision Science Research Center, 402 Worrell Bldg., 924 18th St. So., Birmingham, AL 35294-4390 (E-mail: cbus@uab.edu).

    The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    J Neurophysiol 90: 3838–3853, 2003. First published August 20, 2003; 10.1152/jn.00858.2002.

    3838 0022-3077/03 $5.00 Copyright © 2003 The American Physiological Society www.jn.org

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  • tional evidence for modification of OPN activity during ver- gence is suggested by the observation of Ramat et al. (1999) that random postsaccadic conjugate ocular oscillations occur during combined vergence/saccadic eye movements in hu- mans. The authors interpreted these oscillations as evidence that the postpause resumption of OPN activity was delayed by vergence, allowing irregular firing of the MLBs after the end of the saccade proper. The observations that reduced OPN activ- ity attributed to lesions results in slowed saccades and that vergence reduces OPN activity offer a possible explanation for slowed saccades during vergence. To test this hypothesis, we recorded the activity of OPNs associated with conjugate sac- cades and with saccades during vergence eye movements. OPN activity related to vergence without saccades was also mea- sured. If reduced OPN activity were responsible for the slowed saccades seen during vergence, we would expect to see a significantly lower OPN activity level just before these sac- cades and a positive correlation between presaccadic activity and saccadic slowing.

    Brief reports of some of these results were previously pub- lished (Busettini and Mays 1999; Reusser et al. 1995).

    M E T H O D S

    Pontine omnipause neurons were recorded from 7 juvenile rhesus monkeys (Macaca mulatta) weighting 6–10 kg. All procedures and experimental protocols were approved by the Institutional Animal Care and Use Committee and complied with FDA, AAALAC, and U.S. Public Health Service Policy on the humane care and use of laboratory animals.

    Surgical procedures

    Animals were trained to enter a primate chair before a sequence of aseptic surgical procedures. At the time of the surgery they were given an intramuscular injection of ketamine (Ketalar), and then intubated and maintained on isoflurane for the duration of the surgery. Heart rate, respiratory rate, blood pressure, O2 saturation, and body temper- ature were monitored continuously. During the postsurgical period, animals were given analgesics as needed to alleviate any discomfort, and training or experiments were started only after full recovery from each surgery.

    In the initial surgery, stainless steel plates (Synthes) were attached to the skull with bone screws. A metal post was affixed to these strips with dental acrylic cement for head fixation. Following a protocol similar to that of Judge et al. (1980), a coil of fine wire (Biomed Wire AS633) was implanted under the conjunctiva of the right eye, so that eye position could be monitored using the magnetic search coil technique (Fuchs and Robinson 1966). After the animals reached a satisfactory level of training on simple saccadic and tracking trials, a 2nd eye coil was implanted on the left eye, allowing the monitoring of binocular eye movements. When the monkeys easily performed the more complex in-depth eye movements and preliminary behavioral recordings were completed, 2 recording cylinders were implanted with acrylic cement over 15-mm holes trephined into the skull. The 2 chambers were stereotaxically positioned bilaterally over the brain stem at a 20° angle to the sagittal plane, 14.5 mm lateral from the midline, and 1 or 2 mm anterior to ear-bar zero.

    Behavioral task and visual display

    The animal was placed in a primate chair with its head immobilized and was required to make transfers of fixation in depth and/or direc- tion in response to target motion generated by a mirror haploscope with a system of lenses that matched the accommodative and vergence

    demands (Walton and Mays 2003). A pupil