Effects of Reversible Inactivation of the Primate Mesencephalic Reticular Formation. I. Hypermetric Goal-Directed Saccades

Abstract

Single-neuron recording and electrical microstimulation suggest three roles for the mesencephalic reticular formation (MRF) in oculomotor control: 1) saccade triggering, 2) computation of the horizontal component of saccade amplitude (a feed-forward function), and 3) feedback of an eye velocity signal from the paramedian zone of the pontine reticular formation (PPRF) to higher structures. These ideas were tested using reversible inactivation of the MRF with pressure microinjection of muscimol, a GABA(A) agonist, in four rhesus monkeys prepared for chronic single-neuron and eye movement recording. Reversible inactivation revealed two subregions of the MRF: ventral-caudal and rostral. The ventral-caudal region, which corresponds to the central MRF, the cMRF, or nucleus subcuneiformis, is the focus of this paper and is located lateral to the oculomotor nucleus and caudal to the posterior commissure (PC). Inactivation of the cMRF produced contraversive, upward saccade hypermetria. In three of eight injections, the velocity of hypermetric saccades was too fast for a given saccade amplitude, and saccade duration was shorter. The latency for initiation of most contraversive saccades was markedly reduced. Fixation was also destabilized with the development of macrosaccadic square-wave jerks that were directed toward a contraversive goal in the hypermetric direction. Spontaneous saccades collected in total darkness were also directed toward the same orbital goal, up and to the contraversive side. Three of eight muscimol injections were associated with a shift in the initial position of the eyes. A contralateral head tilt was also observed in 5 out of 8 caudal injections. All ventral-caudal injections with head tilt showed no evidence of vertical postsaccadic drift. This suggested that the observed changes in head movement and posture resulted from inactivation of the caudal MRF and not spread of the muscimol to the interstitial nucleus of Cajal (INC). Evidence of hypermetria strongly supports the idea that the ventral-caudal MRF participates in the feedback control of saccade accuracy. However, development of goal-directed eye movements, as well as a shift in the initial position following some of the cMRF injections, suggest that this region also contributes to the generation of an estimate of target or eye position coded in craniotopic coordinates. Last, the observed reduction in contraversive saccade latency and development of macrosaccadic square-wave jerks supports a role of the MRF in saccade triggering.

Three-Dimensional Eye–Head Coordination After Injection of Muscimol Into the Interstitial Nucleus of Cajal (INC)

“…Finally, the three-dimensional range, although shifted torsionally, retained its characteristic "Fick shape", although with a reduced twist. Similar findings were reported previously during INC inactivation in the cat (Fukushima et al 1985a) and similar contralateral head tilts were observed after reversible inactivation of the rostral mesencephalic reticular formation (MRF) in the primate (Waitzman et al 2000b), which lies adjacent to the INC. This raises the question of whether some of the head tilt observed in our experiments was attributable to spread of muscimol to the MRF.…”

“…Instead, the eye usually rotated in the same direction as the head. This differs from the compensatory eye position shifts observed during ipsiversive head tilts produced by inactivation of the MRF (Waitzman et al 2000a), suggesting that the latter head tilts may have resulted from an imbalance of input to the INC (integrator) without disrupting the INC itself.…”

“…First, the oculomotor deficits that occur during MRF and INC inactivation are quite different (for example, inactivation of the INC always produces integrator failure, whereas injection of muscimol into the MRF does not), so these effects are not easily confused. More important, although the early time course of head tilt after injection of muscimol into the MRF was not reported, 2-3 h after such injections head tilt was relatively small (20 -30°) and occurred after only half the injections (Waitzman et al 2000b). In our experiments head tilt was consistent, appeared fairly quickly after our injections (usually within 15 min), often exceeded 30°during our experiment, and after 2-3 h-after animals were returned to their cage-could sometimes reach values of about 90°, including tilt of the shoulders (by our visual observations).…”

Effect of Reversible Inactivation of Superior Colliculus on Head Movements

“…Typically the injections at different depths were deeper within the SC, and they were most likely confined within the SC because the observed gaze shift impairments were comparable to previously reported head-restrained saccade deficits (e.g., Lee et al 1988). Also inspection of the animal from a camera revealed no visually detectable signs of tilt in head posture, which has been reported to occur after inactivation of the oculomotor regions of the underlying mesencephalic reticular formation (Farshadmanesh et al 2007;Klier et al 2002;Waitzman et al 2000). In all, 45 lidocaine injections were made in 18 electrode penetrations.…”

“…Inactivation of the SC has also been demonstrated to produce deficits in nonsaccadic eye movements, such as smooth pursuit (Basso et al 2000) but, to our knowledge, there are no detailed published data regarding the effects of reversible SC inactivation on gaze shifts in head-unrestrained monkeys. It is known, however, that inactivation of structures downstream of the SC, particularly regions of the mesencephalic reticular formation (Farshadmanesh et al 2007;Klier et al 2002;Waitzman et al 2000), produce severe deficits in head posture. In the present study, reversible inactivation was used to investigate the role of the primate SC in the control of head movements, including not only those that assist in redirecting gaze but also those that occur in the absence of a change in gaze (i.e., vestibuloocular reflex gain equals 1).…”