A distributed saccade-associated network encodes high velocity conjugate and monocular eye movements in the zebrafish hindbrain

Saccades are rapid eye movements that redirect gaze. Their magnitudes and directions are tightly controlled by the oculomotor system, which is capable of generating conjugate, monocular, convergent and divergent saccades. Recent studies suggest a mainly monocular control of saccades in mammals, although the development of binocular control and the interaction of different functional populations is less well understood. For zebrafish, a well-established model in sensorimotor research, the nature of binocular control in this key oculomotor behavior is unknown. Here, we use the optokinetic response and calcium imaging to characterize how the developing zebrafish oculomotor system encodes the diverse repertoire of saccades. We find that neurons with phasic saccade-associated activity (putative burst neurons) are most frequent in dorsal regions of the hindbrain and show elements of both monocular and binocular encoding, revealing a mix of the response types originally hypothesized by Helmholtz and Hering. Additionally, we observed a certain degree of behavior-specific recruitment in individual neurons. Surprisingly, calcium activity is only weakly tuned to saccade size. Instead, saccade size is apparently controlled by a push–pull mechanism of opposing burst neuron populations. Our study reveals the basic layout of a developing vertebrate saccade system and provides a perspective into the evolution of the oculomotor system.

A NEURON-BASED TIME-OPTIMAL CONTROLLER OF HORIZONTAL SACCADIC EYE MOVEMENTS

A neural network model of biophysical neurons in the midbrain for controlling oculomotor muscles during horizontal human saccades is presented. Neural circuitry that includes omnipause neuron, premotor excitatory and inhibitory burst neurons, long lead burst neuron, tonic neuron, interneuron, abducens nucleus and oculomotor nucleus is developed to investigate saccade dynamics. The final motoneuronal signals drive a time-optimal controller that stimulates a linear homeomorphic model of the oculomotor plant. To our knowledge, this is the first report on modeling the neural circuits at both premotor and motor stages of neural activity in saccadic systems.

The Saccadic System

Saccades are fast conjugate eye movements that move both eyes quickly in the same direction, so that the image of an object of interest is brought on the foveae. Saccades can be made not only toward visual targets, but also toward auditory and tactile stimuli, as well as toward memorized targets. Saccades can be generated reflexively, and they are responsible for resetting the eyes back to the mid-orbital position during vestibulo-ocular or optokinetic stimulation. Saccades need to be fast to get the eyes on the target as soon as possible. They also need to be fast because our eyes act like cameras with slow shutters—vision is so blurred during saccades that the eyes have to move quickly to minimize the time during which no clear image is captured on the foveae. Indeed, saccades are the fastest type of eye movements, and they are among the fastest movements that the body can make. Saccade speed is not under voluntary control but depends on the size of the movement, with larger saccades attaining higher peak velocities. It has been estimated that we make more than 100,000 saccades per day. The burst neuron circuits in the brainstem provide the necessary motor signals to the extraocular muscles for the generation of saccades. There is a division of labor between the pons and the midbrain, with the pons primarily involved in generating horizontal saccades and the midbrain primarily involved in generating vertical and torsional saccades. However, because eye movements are a component of cognitive and purposeful behaviors in higher mammals, the process of deciding when and where to make a saccade occurs in the cerebral cortex. Not only does the cortex exert control over saccades through direct projections to the burst neuron circuits, it also acts via the superior colliculus. The superior colliculus is located in the midbrain and consists of seven layers: three superficial layers and four intermediate/ deep layers. The three superficial layers receive direct inputs from both the retina and striate cortex, and they contain a retinotopic representation of the contralateral visual hemifield.

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.

Symmetry of oculomotor burst neuron coordinates about Listing's plane

1. The purpose of this investigation was to determine the axes of eye rotation generated by oculomotor burst neuron populations and the coordinate system that they collectively define. In particular, we asked if such coordinates might be related to constraints in the emergent behavior, i.e., Listing's law for saccades. 2. The mesencephalic rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) was identified in four monkeys with the use of single-unit recording, and then explored with the use of electrical microstimulation and pharmacological inactivation with the inhibitory gamma-aminobutyric acid (GABA) agonist muscimol. Three-dimensional (3-D) eye positions and velocities were recorded in one or both eyes while alert animals made eye movements in response to visual stimuli and head rotation. 3. Unilateral stimulation of the riMLF (20 microA, 200 Hz, 300-600 ms) produced conjugate, constant velocity eye rotations, which then stopped abruptly and held their final positions. This is expected if the riMLF produces phasic signals upstream from the oculomotor integrator. 4. Units that burst before upward or downward saccades were recorded intermingled in each side of the riMLF. Unilateral stimulation of the same riMLF sites produced eye rotations about primarily torsional axes, clockwise (CW) during right riMLF stimulation and counterclockwise (CCW) during left stimulation. Only small and inconsistent vertical components were observed, supporting the view that the riMLF carries intermingled up and down signals. 5. The torsional axes of eye rotation produced by riMLF stimulation did not correlate to external anatomic landmarks. Instead, stimulation axes from both riMLF sides aligned with the primary gaze direction orthogonal to Listing's plane of eye positions recorded during saccades. 6. Injection of muscimol into one side of the riMLF produced a conjugate deficit in saccades and quick phases, including a 50% reduction in all vertical velocities and complete loss of one torsional direction. CW was lost after right riMLF inactivation, and CCW was lost after left inactivation. 7. The plane that separated the intact torsional axes from the missing axes correlated with the orientation of Listing's plane. Thus, during left or right riMLF inactivation, the vertical axes of intact horizontal saccades were abnormally aligned with Listing's plane. The orientation of these axes was not correlated with external anatomic landmarks. 8. As suggested by their alignment with Listing's plane, the intact vertical axes of horizontal saccades following riMLF inactivation were orthogonal to torsional riMLF stimulation axes.(ABSTRACT TRUNCATED AT 400 WORDS)

REM sleep burst neurons, PGO waves, and eye movement information

Pontogeniculooccipital (PGO) waves appeared almost simultaneously in both lateral geniculate nuclei (LGB), but in each case on had a larger amplitude and preceded the other by a few milliseconds. The larger, earlier wave is called the primary wave. Primary waves were found to appear with equal frequency in each LGB. During rapid eye movement sleep (REM sleep), LGB primary waves were ipsilateral to the direction of rapid eye movements. During REM sleep a group of cat midbrain neurons, which we call PGO burst cells, fired in stereotyped bursts at fixed latencies before ipsilateral primary waves, but they almost never fired bursts when the primary waves were contralateral. PGO burst neuron discharge also correlated with the direction of rapid eye movements during REM sleep. In wakefulness, PGO burst cells fired single spikes, not bursts, which had some correlation with LGB waves when averaged by computer. The results suggest that PGO burst cells are output elements in the PGO wave-generation system ad that PGO waves convey eye movement information to the sensory visual system in REM sleep. They also may have a role in the production of saccade-related waves in the visual system during wakefulness.