Michael J. Mustari

An aberrant crossed visual corticotectal pathway in albino rats

This study investigates the dynamic nature of the developing corticotectal pathway arising in the visual cortex. Special attention is given to the interaction occurring between the corticotectal pathways of each side of the brain and between corticotectal and retinotectal terminations. Normally the visual cortex of rats projects only to the ipsilateral superior colliculus. If one visual cortex is removed at birth, the remaining visual cortex subsequently shows a bilateral projection to the superior colliculus. The aberrant corticotectal pathway is heavier if the cortical ablation is accompanied by eye removal at birth but eye enucleation alone is not a sufficient stimulus for production of a crossed corticotectal projection. The aberrant crossed pathway shows a topographic order which appears to correspond to that of the normal ipsilateral corticotectal pathway. The pathway differs from the aberrant projections from the retina in that lesions done as late as 20 days postnatal still result in an aberrant crossed corticotectal pathway. This is similar to the aberrant crossed cortical projections from sensorimotor cortex. The pathway would appear to arise as a result of lack of competition from corticotectal axons normally present contralaterally or from attraction of denervated corticotectal sites. While denervated retinotectal sites stimulate sprouting of the corticotectal axons once in the deafferented colliculus, they do not stimulate crossing of the corticotectal projection.

Saccadic modulation of neural responses: possible roles in saccadic suppression, enhancement, and time compression.

Humans use saccadic eye movements to make frequent gaze changes, yet the associated full-field image motion is not perceived. The theory of saccadic suppression has been proposed to account for this phenomenon, but it is not clear whether suppression originates from a retinal signal at saccade onset or from the brain before saccade onset. Perceptually, visual sensitivity is reduced before saccades and enhanced afterward. Over the same time period, the perception of time is compressed and even inverted. We explore the origins and neural basis of these effects by recording from neurons in the dorsal medial superior temporal area (MSTd) of alert macaque monkeys. Neuronal responses to flashed presentations of a textured pattern presented at random times relative to saccades exhibit a stereotypical pattern of modulation. Response amplitudes are strongly suppressed for flashes presented up to 90 ms before saccades. Immediately after the suppression, there is a period of 200–450 ms in which flashes generate enhanced response amplitudes. Our results show that (1) MSTd is not directly suppressed, rather suppression is inherited from earlier visual areas; (2) early suppression of the visual system must be of extra-retinal origin; (3) postsaccadic enhancement of neural activity occurs in MSTd; and (4) the enhanced responses have reduced latencies. As a whole, these observations reveal response properties that could account for perceptual observations relating to presaccadic suppression, postsaccadic enhancement and time compression.

Animal Models for Visual Deprivation‐Induced Strabismus and Nystagmus

Abstract: The development of gaze‐stabilizing systems depends on normal vision during infancy. Monkeys reared with binocular lid suture (BLS) for the first 25‐40 days of life have strabismus, optokinetic nystagmus deficits, latent nystagmus, and decreased binocular cells in the visual cortex and nucleus of the optic tract. When BLS is extended to 55 days, pendular and congenital nystagmus also occurs. Eyelids in infant monkeys are hairless and thin, but BLS still degrades sensory fusion, motion, and form perception. To determine to what extent these visual properties are critical in the development of normal gaze stabilization, we examined infant monkeys reared with one opaque contact lens over one eye, alternated to the fellow eye every other day (AMO); and monkeys reared in a 3‐Hz strobe environment. Monkeys reared with AMO develop strabismus, but have normal optokinetic nystagmus and no spontaneous nystagmus. Area 17 is monocular, but the medial temporal area and the nucleus of the optic tract are binocular. Monkeys reared in strobe light develop pendular nystagmus but not strabismus. We were puzzled by the results of the AMO monkeys until we examined infant monkeys with BLS that were prevented from seeing form through the lids. This was done by leaving the tarsal plate intact behind the eyelid. They developed similar to the AMO monkeys. These results suggest that disruption of sensory fusion during infancy (BLS, AMO) causes strabismus. If strabismus occurs while the monkeys have some form vision from each eye (BLS without tarsal plate), then the nucleus of the optic tract becomes monocular, which causes optokinetic nystagmus deficits and latent nystagmus. Infant monkeys reared without visual motion develop pendular nystagmus.

Histogenesis of the superior colliculus of the albino rat: A tritiated thymidine study

The pattern of generation of neurons in the albino rat superior colliculus has been studied in adult and fetal material. Neurons are generated between embryonic days 12 to 17, with rostrolateral colliculus in advance of caudomedial parts. More of the cells contributing to the deeper layers are generated early, while more of the later generated cells are located superficially. The cells of individual laminae are not formed on specific days as in the cortex, nor are the complicated gradients described previously for the chick optic tectum evident. While the largest cells (found deep in the colliculus) are among the first formed and the small marginal cells among the last, there is in general a broad range of cell size being generated at any one time. The observed patterns are consistent with the concept of simultaneous production of several cell types from the ventricular epithelium on any given day. Studies of material at short times after [3H]thymidine injection allow correlation of the time of arrival of cells in their appropriate layer with time of arrival of afferents. In addition they suggest that factors controlling the final placement of cells in the mature nervous system is a very complex process and may involve some form of intercellular recognition.

Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: A dual retrograde tracing study

The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT‐DTN) along with the dorsolateral pontine nucleus (DLPN) have been shown to play a role in controlling slow eye movements and in maintaining stable vision during head movements. Both nuclei are known to receive cortical input from striate and extrastriate cortex. To determine to what degree this cortical input arises from the same areas and potentially from the same individual neurons, we placed different retrograde tracers into the NOT‐DTN and the DLPN. In the ipsilateral cortical hemisphere the two projections mainly overlapped in the posterior part of the superior temporal sulcus (STS) comprising the middle temporal area (MT), the middle superior temporal area (MST), and the visual area in the fundus of the STS (FST) and the surrounding cortex. In these areas, neurons projecting to the NOT‐DTN or the DLPN were closely intermingled. Nevertheless, only 3–11% of the labeled neurons in MT and MST were double‐labeled in our various cases. These results indicate that the cortical input to the NOT‐DTN and DLPN arises from largely separate neuronal subpopulations in the motion sensitive areas in the posterior STS. Only a small percentage of the projection neurons bifurcate to supply both targets. These findings are discussed in relation to the optokinetic and the smooth pursuit system. J. Comp. Neurol. 444:144–158, 2002.

A Theory of the Dual Pathways for Smooth Pursuit Based on Dynamic Gain Control

The smooth pursuit eye movement (SPEM) system is much more sensitive to target motion perturbations during pursuit than during fixation. This sensitivity is commonly attributed to a dynamic gain control mechanism. Neither the neural substrate nor the functional architecture for this gain control has been fully revealed. There are at least two cortical areas that crucially contribute to smooth pursuit and are therefore eligible sites for dynamic gain control: the medial superior temporal area (MST) and the pursuit area of the frontal eye fields (FEFs), which both project to brain stem premotor structures via parallel pathways. The aim of this study was to develop a model of smooth pursuit based on behavioral, anatomical, and neurophysiological results to account for nonlinear dynamic gain control. Using a behavioral paradigm in humans consisting of a sinusoidal oscillation (4 Hz, +/-8 degrees/s) superimposed on a constant velocity target motion (0-24 degrees/s), we were able to identify relevant gain control parameters in the model. A salient feature of our model is the emergence of two parallel pathways from higher visual cortical to lower motor areas in the brain stem that correspond to the MST and FEF pathways. Detailed analysis of the model revealed that one pathway mainly carries eye velocity related signals, whereas the other is associated mostly with eye acceleration. From comparison with known neurophysiological results we conclude that the dynamic gain control can be attributed to the FEF pathway, whereas the MST pathway serves as the basic circuit for maintaining an ongoing SPEM.

Incomitance in Monkeys with Strabismus

Purpose: Rhesus monkeys reared with restricted visual environment during their first few months of life develop large ocular misalignment (strabismus). The purpose of this study was to describe ‘A and V’ patterns and DVD in these animals during fixation and eye movements and suggest that this form of rearing produces animals that are a suitable model to study mechanisms that might cause ‘A/V’ pattern incomitant strabismus and dissociated vertical deviation (DVD) in humans. Methods: Eye movements were recorded during fixation, smooth-pursuit and saccades using binocular search coils in one monkey with esotropia, three monkeys with exotropia and one normal monkey. Results: 1) Monkeys reared with Alternating Monocular Occlusion or Binocular deprivation (tarsal plates intact) showed both horizontal and vertical misalignment during monocular and binocular viewing. 2) Large ‘A’ patterns were evident in 2 out of 3 exotropes while a ‘V’ pattern was observed in the esotrope. 3) Similar ‘A/V’ patterns were observed with either eye viewing and during fixation or eye movements. 4) The vertical misalignment, which consisted of the non-viewing eye being higher than the fixating eye, appeared to constitute a DVD. Conclusion: Visual sensory deprivation methods that induce large strabismus also induce ‘A/V’ patterns and DVD similar to certain types of human strabismus. The source of the pattern strabismus could be central, i.e., altered innervation to extraocular muscles from motor nuclei, or peripheral, i.e., altered location of extraocular muscle pulleys.

Signal Processing and Distribution in Cortical‐Brainstem Pathways for Smooth Pursuit Eye Movements

Smooth pursuit (SP) eye movements are used to maintain the image of a moving object relatively stable on the fovea. Even when tracking a single target over a dark background, multiple areas including frontal eye fields (FEF) and middle temporal (MT) and medial superior temporal (MST) cortex contribute to converting visual signals into initial commands for SP. Signals in the cortical pursuit system reach the oculomotor cerebellum through brainstem centers including the dorsolateral pontine nucleus (DLPN), nucleus reticularis tegmenti pontis (NRTP), and pretectal nucleus of the optic tract (NOT). The relative information carried in these parallel pathways remains to be fully defined. We used multiple linear‐regression modeling to estimate the relative sensitivities of cortical (MST, FEF), pontine (NRTP, DLPN), and NOT neurons to eye‐ and retinal‐error parameters (position, velocity, and acceleration) during step‐ramp SP of macaques (Macaca mulatta). We found that a large proportion of pursuit‐related MST and DLPN neurons were most sensitive to eye‐velocity or retinal error velocity. In contrast, a large proportion of FEF and rostral NRTP neurons were most sensitive to eye acceleration. Visual neurons in MST, DLPN, and NOT were most sensitive to retinal image velocity.

Smooth Pursuit–Related Information Processing in Frontal Eye Field Neurons that Project to the NRTP

The cortical pursuit system begins the process of transforming visual signals into commands for smooth pursuit (SP) eye movements. The frontal eye field (FEF), located in the fundus of arcuate sulcus, is known to play a role in SP and gaze pursuit movements. This role is supported, at least in part, by FEF projections to the rostral nucleus reticularis tegmenti pontis (rNRTP), which in turn projects heavily to the cerebellar vermis. However, the functional characteristics of SP-related FEF neurons that project to rNRTP have never been described. Therefore, we used microelectrical stimulation (ES) to deliver single pulses (50–200 μA, 200-μs duration) in rNRTP to antidromically activate FEF neurons. We estimated the eye or retinal error motion sensitivity (position, velocity, and acceleration) of FEF neurons during SP using multiple linear regression modeling. FEF neurons that projected to rNRTP were most sensitive to eye acceleration. In contrast, FEF neurons not activated following ES of rNRTP were often most sensitive to eye velocity. In similar modeling studies, we found that rNRTP neurons were also biased toward eye acceleration. Therefore, our results suggest that neurons in the FEF–rNRTP pathway carry signals that could play a primary role in initiation of SP.

Do Palisade Endings in Extraocular Muscles Arise from Neurons in the Motor Nuclei

PURPOSE The purpose of this study was to localize the cell bodies of palisade endings that are associated with the myotendinous junctions of the extraocular muscles. METHODS Rhesus monkeys received tract-tracer injections (tetramethylrhodamine dextran [TMR-DA] or choleratoxin subunit B [CTB]) into the oculomotor and trochlear nuclei, which contain the motoneurons of extraocular muscles. All extraocular muscles were processed for the combined immunocytochemical detection of the tracer and SNAP-25 or synaptophysin for the visualization of the complete muscle innervation. RESULTS In all muscles--except the lateral rectus--en plaque and en grappe motor endings, but also palisade endings, were anterogradely labeled. In addition a few tracer-labeled tendon organs were found. One group of tracer-negative nerve fibers was identified as thin tyrosine hydroxylase-positive sympathetic fibers, and a second less numerous group of tracer-negative fibers may originate from the trigeminal ganglia. No cellular or terminal tracer labeling was present within the mesencephalic trigeminal nucleus or the trigeminal ganglia. CONCLUSIONS These results confirm those of earlier studies and furthermore suggest that the somata of palisade endings are located close to the extraocular motor nuclei--in this case, probably within the C and S groups around the periphery of the oculomotor nucleus. The multiple en grappe endings have also been shown to arise from these cells groups, but it is not possible to distinguish different populations in these experiments.