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Anatomical studies in goldfish show that the tectofugal axons provide a large number of boutons within the mesencephalic reticular formation. Electrical stimulation, reversible inactivation and cell recording in the primate central mesencephalic reticular formation have suggested that it participates in the control of rapid eye movements (saccades). Moreover, the role of this tecto-recipient area in the generation of saccadic eye movements in fish is unknown. In this study we show that the electrical microstimulation of the mesencephalic reticular formation of goldfish evoked short latency saccadic eye movements in any direction (contraversive or ipsiversive, upward or downward). Movements of the eyes were usually disjunctive. Based on the location of the sites from which eye movements were evoked and the preferred saccade direction, eye movements were divided into different groups: pure vertical saccades were mainly elicited from the rostral mesencephalic reticular formation, while oblique and pure horizontal were largely evoked from middle and caudal mesencephalic reticular formation zones. The direction and amplitude of pure vertical and horizontal saccades were unaffected by initial eye position. However the amplitude, but not the direction of most oblique saccades was systematically modified by initial eye position. At the same time, the amplitude of elicited saccades did not vary in any consistent manner along either the anteroposterior, dorsoventral or mediolateral axes (i.e. there was no topographic organization of the mesencephalic reticular formation with respect to amplitude). In addition to these groups of movements, we found convergent and goal-directed saccades evoked primarily from the anterior and posterior mesencephalic reticular formation, respectively. Finally, the metric and kinetic characteristics of saccades could be manipulated by changes in the stimulation parameters. We conclude that the mesencephalic reticular formation in goldfish shares physiological functions that correspond closely with those found in mammals.

Neurones in the central mesencephalic reticular formation (cMRF) begin to discharge prior to saccades. These long lead burst neurones interact with major oculomotor centres including the superior colliculus (SC) and the paramedian pontine reticular formation (PPRF). Three different functions have been proposed for neurones in the cMRF: (1) to carry eye velocity signals that provide efference copy information to the SC (feedback), (2) to provide duration signals from the omnipause neurones to the SC (feedback), or (3) to participate in the transformation from the spatial encoding of a target selection signal in the SC into the temporal pattern of discharge used to drive the excitatory burst neurones in the pons (feed-forward). According to each respective proposal, specific predictions about cMRF neuronal discharge have been formulated. Individual neurones should: (1) encode instantaneous eye velocity, (2) burst specifically in relation to saccade duration but not to other saccade metrics, or (3) have a spectrum of weak to strong correlations to saccade dynamics. To determine if cMRF neurones could subserve these multiple oculomotor roles, we examined neuronal activity in relation to a variety of saccade metrics including amplitude, velocity and duration. We found separate groups of cMRF neurones that have the characteristics predicted by each of the proposed models. We also identified a number of subgroups for which no specific model prediction had previously been established. We found that we could accurately predict the neuronal firing pattern during one type of saccade behaviour (visually guided) using the activity during an alternative behaviour with different saccade metrics (memory guided saccades). We suggest that this evidence of a close relationship of cMRF neuronal discharge to individual saccade metrics supports the hypothesis that the cMRF participates in multiple saccade control pathways carrying saccade amplitude, velocity and duration information within the brainstem.

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.

Electrical microstimulation and single-unit recording have suggested that a group of long-lead burst neurons (LLBNs) in the mesencephalic reticular formation (MRF) just lateral to the interstitial nucleus of Cajal (INC) (the peri-INC MRF, piMRF) may play a role in the generation of vertical rapid eye movements. Inactivation of this region with muscimol (a GABA(A) agonist) rapidly produced vertical saccade hypometria (6 injections). In three of six injections, there was a marked reduction in the velocity of vertical saccades out of proportion to saccade amplitude (i.e., saccades fell below the main sequence). This was associated with a moderate increase in saccade duration. Inadvertent inactivation of the INC could not account for these observations because vertical, postsaccadic drift was not observed. Similarly, pure downward saccade hypometria, the hallmark of rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) inactivation, was always preceded by loss of upward saccades in our experiments. We also found a downward and ipsiversive displacement of initial eye position and evidence of a contraversive head tilt following piMRF injections. Saccade latency was shorter after two of six injections. Simulation of a local feedback model provided three possible explanations for vertical saccade hypometria: 1) a shift in the input to the model to request smaller saccades, 2) a reduction of LLBN input to the vertical saccade medium lead burst neurons (MLBNs), or 3) an increase in the gain of the feedback pathway. However, when the second hypothesis was coupled to a shortened duration of the saccade trigger (i.e., the discharge of the omnipause neurons), the physiological observations of piMRF inactivation could be replicated. This suggested that muscimol had targeted structures that provided both long-lead burst activity to the MLBNs in the riMLF and were critical for reactivation of the omnipause neurons. Evidence of markedly reduced vertical saccade amplitude, curved saccade trajectories, increased saccade duration, and saccades that fall below the amplitude/velocity main sequence in these monkeys closely parallels the oculomotor findings of patients with progressive supranuclear palsy (PSP).

1. One hundred twenty neurons were recorded in the central mesencephalic reticular formation (cMRF) of four rhesus monkeys, trained to make visually guided and targeted saccadic eye movements. Eye movements were recorded with the head fixed, using electrooculography (EOG) or subconjunctival scleral search coils. Seventy-six percent (92/120) of cells discharged before and during contraversive visually guided or targeted rapid eye movements, and 76% of these (70/92) responded during contraversive spontaneous saccades in the dark. cMRF neurons had large contraversive movement fields and either a high (> 10 spikes/s) or low background level of spontaneous activity in the dark. The optimal movement vectors (i.e., saccades with greatest response) were predominantly horizontal, although many had a vertical component. Cells with optimal movement vectors within +/- 25 degrees of pure vertical were more rostral in the MRF and were excluded from the analysis. 2. A subgroup of cMRF neurons (31 of 92) that discharged before and during visually guided saccades were examined for visual sensitivity. Slightly less than one-half of these cells (42%, 13/31) were visuomotor units, i.e., they responded to visual targets in the absence of eye movement. The other 58% (n = 18) did not discharge during the visual probe trial; they were movement-related cells. 3. Microstimulation (threshold 40-60 microA at 333 Hz) at the sites of many of these cMRF neurons produced contraversive saccadic eye movements at short latency (< 40 ms). The amplitude and direction of the elicited saccades were similar to the optimal movement vector determined from single-unit recording. This suggested that cMRF cells recorded at the same locus of electrical microstimulation participated in the network responsible for the production and control of rapid eye movements. 4. The 92 saccade-related neurons were divided into two groups on the basis of their background discharge rate. Firing rates for both low background (28%, n = 26) and high background (72%, n = 66) cells increased approximately 30 ms before contraversive saccades and reached a peak discharge just before saccade onset. The low background neurons had either no activity or generated a few spikes just before the end of ipsiversive saccades. The steady rate of discharge (> 10 spikes/s) of high background neurons was inhibited from approximately 20 ms before ipsiversive saccades until just before saccade end. 5. Cells were also subdivided on the basis of how their discharge rates fell at the end of saccades. Clipped cells (38%, n = 35) had activity that fell sharply with saccade offset. Partially clipped cells (62%, n = 57) had persistent firing in the 100 ms following the saccade that was > 20% higher than the firing during the 100 ms before the saccade. 6. Latencies between the 90% point on the rising edge of the peak discharge and the start of the saccade were < or = 5.3 ms for eye movement-related cells in two monkeys. Longer latencies (11-19 ms) were found when measured between the 10% point on the rising edge of the peak discharge and saccade onset. These latencies were equal to or shorter than those obtained for eye movement-related burst neurons in the intermediate and deep layers of the superior colliculus analyzed similarly. Delays between the peak discharge and peak eye velocity were 13.6-15.1 ms for the same group of cMRF eye movement-related cells. These were significantly shorter than the delays measured for eye movement neurons in the superior colliculus (SC) of one of the monkeys. These findings suggest that the buildup discharge of cMRF neurons occurs early enough before saccades to contribute to saccade triggering. The peak discharge, however, occurs with or after the burst in the SC, suggesting that this portion of the discharge serves a function other than saccade triggering. 7. The number of spikes in bursts associated with eye movement was correlated with saccade parameters.