Jérome Fleuriet

Saccadic Interception of a Moving Visual Target after a Spatiotemporal Perturbation

Animals can make saccadic eye movements to intercept a moving object at the right place and time. Such interceptive saccades indicate that, despite variable sensorimotor delays, the brain is able to estimate the current spatiotemporal (hic et nunc) coordinates of a target at saccade end. The present work further tests the robustness of this estimate in the monkey when a change in eye position and a delay are experimentally added before the onset of the saccade and in the absence of visual feedback. These perturbations are induced by brief microstimulation in the deep superior colliculus (dSC). When the microstimulation moves the eyes in the direction opposite to the target motion, a correction saccade brings gaze back on the target path or very near. When it moves the eye in the same direction, the performance is more variable and depends on the stimulated sites. Saccades fall ahead of the target with an error that increases when the stimulation is applied more caudally in the dSC. The numerous cases of compensation indicate that the brain is able to maintain an accurate and robust estimate of the location of the moving target. The inaccuracies observed when stimulating the dSC that encodes the visual field traversed by the target indicate that dSC microstimulation can interfere with signals encoding the target motion path. The results are discussed within the framework of the dual-drive and the remapping hypotheses.

Temporal Dynamics of 2D Motion Integration for Ocular Following in Macaque Monkeys

Several recent studies have shown that extracting pattern motion direction is a dynamical process where edge motion is first extracted and pattern-related information is encoded with a small time lag by MT neurons. A similar dynamics was found for human reflexive or voluntary tracking. Here, we bring an essential, but still missing, piece of information by documenting macaque ocular following responses to gratings, unikinetic plaids, and barber-poles. We found that ocular tracking was always initiated first in the grating motion direction with ultra-short latencies (approximately 55 ms). A second component was driven only 10-15 ms later, rotating tracking toward pattern motion direction. At the end the open-loop period, tracking direction was aligned with pattern motion direction (plaids) or the average of the line-ending motion directions (barber-poles). We characterized the dependency on contrast of each component. Both timing and direction of ocular following were quantitatively very consistent with the dynamics of neuronal responses reported by others. Overall, we found a remarkable consistency between neuronal dynamics and monkey behavior, advocating for a direct link between the neuronal solution of the aperture problem and primate perception and action.

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

Purpose Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. Methods We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. Results We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Conclusions Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract

Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates.

PURPOSE We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity. METHODS The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls. RESULTS No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone. CONCLUSIONS We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM.

Behavioural evidence for a visual and proprioceptive control of head roll in hoverflies (Episyrphus balteatus).

ABSTRACT The ability of hoverflies to control their head orientation with respect to their body contributes importantly to their agility and their autonomous navigation abilities. Many tasks performed by this insect during flight, especially while hovering, involve a head stabilization reflex. This reflex, which is mediated by multisensory channels, prevents the visual processing from being disturbed by motion blur and maintains a consistent perception of the visual environment. The so-called dorsal light response (DLR) is another head control reflex, which makes insects sensitive to the brightest part of the visual field. In this study, we experimentally validate and quantify the control loop driving the head roll with respect to the horizon in hoverflies. The new approach developed here consisted of using an upside-down horizon in a body roll paradigm. In this unusual configuration, tethered flying hoverflies surprisingly no longer use purely vision-based control for head stabilization. These results shed new light on the role of neck proprioceptor organs in head and body stabilization with respect to the horizon. Based on the responses obtained with male and female hoverflies, an improved model was then developed in which the output signals delivered by the neck proprioceptor organs are combined with the visual error in the estimated position of the body roll. An internal estimation of the body roll angle with respect to the horizon might explain the extremely accurate flight performances achieved by some hovering insects. Summary: Tethered flying hoverflies shed new light on a proprioception role to stabilize the body roll.

Adaptability of the Immature Ocular Motor Control System: Unilateral IGF-1 Medial Rectus Treatment

PURPOSE Unilateral treatment with sustained release IGF-1 to one medial rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop as a result of changes in extraocular muscles during the critical period of development of binocularity. METHODS Sustained release IGF-1 pellets were implanted unilaterally on one medial rectus muscle in normal infant monkeys during the first 2 weeks of life. Eye position was monitored using standard photographic methods. After 3 months of treatment, myofiber and neuromuscular size, myosin composition, and innervation density were quantified in all rectus muscles and compared to those in age-matched controls. RESULTS Sustained unilateral IGF-1 treatments resulted in strabismus for all treated subjects; 3 of the 4 subjects had a clinically significant strabismus of more than 10°. Both the treated medial rectus and the untreated ipsilateral antagonist lateral rectus muscles had significantly larger myofibers. No adaptation in myofiber size occurred in the contralateral functionally yoked lateral rectus or in myosin composition, neuromuscular junction size, or nerve density. CONCLUSIONS Sustained unilateral IGF-1 treatment to extraocular muscles during the sensitive period of development of orthotropic eye alignment and binocularity was sufficient to disturb ocular motor development, resulting in strabismus in infant monkeys. This could be due to altering fusion of gaze during the early sensitive period. Serial measurements of eye alignment suggested the IGF-1-treated infants received insufficient coordinated binocular experience, preventing the establishment of normal eye alignment. Our results uniquely suggest that abnormal signaling by the extraocular muscles may be a cause of strabismus.

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements.

Temporal Dynamics of Retinal and Extraretinal Signals in the FEFsem during Smooth Pursuit Eye Movements

Neurons in the smooth eye movement subregion of the frontal eye field (FEFsem) are known to play an important role in voluntary smooth pursuit eye movements. Underlying this function are projections to parietal and prefrontal visual association areas and subcortical structures, all known to play vital but differing roles in the execution of smooth pursuit. Additionally, the FEFsem has been shown to carry a diverse array of signals (e.g., eye velocity, acceleration, gain control). We hypothesized that distinct subpopulations of FEFsem neurons subserve these diverse functions and projections, and that the relative weights of retinal and extraretinal signals could form the basis for categorization of units. To investigate this, we used a step-ramp tracking task with a target blink to determine the relative contributions of retinal and extraretinal signals in individual FEFsem neurons throughout pursuit. We found that the contributions of retinal and extraretinal signals to neuronal activity and behavior change throughout the time course of pursuit. A clustering algorithm revealed three distinct neuronal subpopulations: cluster 1 was defined by a higher sensitivity to eye velocity, acceleration, and retinal image motion; cluster 2 had greater activity during blinks; and cluster 3 had significantly greater eye position sensitivity. We also performed a comparison with a sample of medial superior temporal neurons to assess similarities and differences between the two areas. Our results indicate the utility of simple tests such as the target blink for parsing the complex and multifaceted roles of cortical areas in behavior.NEW & NOTEWORTHY The frontal eye field (FEF) is known to play a critical role in volitional smooth pursuit, carrying a variety of signals that are distributed throughout the brain. This study used a novel application of a target blink task during step ramp tracking to determine, in combination with a clustering algorithm, the relative contributions of retinal and extraretinal signals to FEF activity and the extent to which these contributions could form the basis for a categorization of neurons.

A Subset of Palisade Endings Only in the Medial and Inferior Rectus Muscle in Monkey Contain Calretinin

Purpose To further chemically characterize palisade endings in extraocular muscles in rhesus monkeys. Methods Extraocular muscles of three rhesus monkeys were studied for expression of the calcium-binding protein calretinin (CR) in palisade endings and multiple endings. The complete innervation was visualized with antibodies against the synaptosomal-associated protein of 25 kDa and combined with immunofluorescence for CR. Six rhesus monkeys received tracer injections of choleratoxin subunit B or wheat germ agglutinin into either the belly or distal myotendinous junction of the medial or inferior rectus muscle to allow retrograde tracing in the C-group of the oculomotor nucleus. Double-immunofluorescence methods were used to study the CR content in retrogradely labeled neurons in the C-group. Results A subgroup of palisade and multiple endings was found to express CR, only in the medial and inferior rectus muscle. In contrast, the en plaque endings lacked CR. Accordingly, within the tracer-labeled neurons of the C-group, a subgroup expressed CR. Conclusions The study indicates that two different neuron populations targeting nontwitch muscle fibers are present within the C-group for inferior rectus and medial rectus, respectively, one expressing CR, one lacking CR. It is possible that the CR-negative neurons represent the basic population for all extraocular muscles, whereas the CR-positive neurons giving rise to CR-positive palisade endings represent a specialized, perhaps more excitable type of nerve ending in the medial and inferior rectus muscles, being more active in vergence. The malfunction of this CR-positive population of neurons that target nontwitch muscle fibers could play a significant role in strabismus.

Visualizing Neuronal Adaptation Over Time After Treatment of Strabismus

Jérome Fleuriet and Linda K. McLoon Washington National Primate Research Center, University of Washington, Seattle, Washington, United States Department of Ophthalmology, University of Washington, Seattle, Washington, United States Department of Ophthalmology and Visual Neurosciences, Minneapolis, Minnesota, United States; mcloo001@umn.edu Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States