Afferents to the abducens nucleus in the monkey and cat.

The abducens nucleus is a central coordinating element in the generation of conjugate horizontal eye movements. As such, it should receive and combine information relevant to visual fixation, saccadic eye movements, and smooth eye movements evoked by vestibular and visual stimuli. To reveal possible sources of these signals, we retrogradely labeled the afferents to the abducens nucleus by electrophoretically injecting horseradish peroxidase into an abducens nucleus in four monkeys and two cats. The histologic material was processed by the tetramethyl benzidine (TMB) method of Mesulam. In both species the largest source of afferents to the abducens nucleus was bilateral projections from the ventrolateral vestibular nucleus and the rostral pole of the medial vestibular nucleus. Scattered neurons were also labeled in the middle and caudal levels of the medial vestibular nucleus. Large numbers of neurons were labeled in the ventral margin of the nucleus prepositus hypoglossi in the cat and in the common margin of the nucleus prepositus and the medial vestibular nucleus in the monkey, a region we call the marginal zone. Substantial numbers of retrogradely labeled neurons were found in the dorsomedial pontine reticular formation both caudal and rostral to the abducens nuclei. In the monkey, large numbers of labeled neurons were present in the contralateral medial rectus subdivision of the oculomotor complex, while smaller numbers occurred in the ipsilateral medial rectus subdivision and elsewhere in the oculomotor complex. In the cat, large numbers of retrogradely labeled cells were present in a small periaqueductal gray nucleus immediately dorsal to the caudal pole of the oculomotor complex, and a few labeled neurons were also dispersed through the caudal part of the oculomotor complex. Occasional labeled neurons were present in the contralateral superior colliculus in both species. The size and distribution of the labeled neurons within the intermediate gray differed dramatically in the two species. In the cat, the retrogradely labeled neurons were very large and occurred predominantly in the central region of the colliculus, while in the monkey, they were small to intermediate in size and were distributed more uniformly within the middle gray. Among the afferent populations present in the monkey, but not in the cat, was a group of scattered neurons in the ipsilateral rostral interstitial nucleus of the medial longitudinal fasciculus and a denser, bilateral population in the interstitial nucleus of Cajal.(ABSTRACT TRUNCATED AT 400 WORDS)

Coordination of gaze shifts in primates: brainstem inputs to neck and extraocular motoneuron pools.

To determine whether there are brainstem regions that provide common input to the motoneurons that move both the head and the eyes, we injected wheat germ agglutinin-horseradish peroxidase complex (WGA-HRP) into neck motoneuron pools at spinal level C2 (N = 3) and extraocular motoneuron pools in the abducens (N = 1) and oculomotor/trochlear (N = 1) nuclei of rhesus and fascicularis macaques. We also injected WGA-HRP into spinal level C5-7 (N = 1) of a fascicularis macaque for comparison. After injections into C2, we observed retrogradely labeled cells in the ventral reticular formation (NRV), the gigantocellular reticular formation (NRG), and both the oral (NRPO) and the caudal (NRPC) divisions of the paramedian pontine reticular formation (PPRF). There was also a column of labeled cells in the cuneate reticular nucleus (NCUN) just lateral to the ipsilateral periaqueductal gray (PAG). This column extended rostrally into the central mesencephalic reticular formation (CMRF). In addition, there were labeled cells in the region ventral and caudal to the rostral interstitial nucleus of the MLF (riMLF), the area lateral to the interstitial nucleus of Cajal (INC), and the ventral part of the lateral vestibular nucleus (LVN) and lateral part of the medial vestibular nucleus (MVN). There were also a few labeled cells in the fastigial (FN) and interposed (IN) nuclei of the cerebellum but very few in the superior colliculus (SC). In contrast, the injection into C5-7 labeled many cells in the lateral vestibular nucleus (LVN) and very few in FN or IN. Injecting WGA-HRP into the abducens nucleus and the surrounding tissue labeled many cells in SC, PPRF, MVN, FN, and nucleus prepositus hypoglossi (NPH). Injecting into the oculomotor/trochlear nuclei and nearby tissue labeled cells in SC, INC, riMLF, FN, IN, MVN, and superior vestibular nucleus (SVN). Structures that project to both neck and eye motoneuron pools, and therefore probably participate in both head and eye movements, include the lateral part of the MVN and both NRPO and NRPC in the PPRF. Those that project primarily to neck motoneurons in C2 include the NRV, the NRG, and the NCUN-CMRF column. Those projecting exclusively to extraocular nuclei include the NPH, INC, riMLF, NRPD, and SC. We use these data to propose a scheme for control of combined eye-head movements in monkeys.

Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase.

To investigate the afferent projections to the flocculus in a nonhuman primate, we injected horseradish peroxidase into one flocculus of six rhesus macaques (Macaca mulatta) and processed their brains according to the tetramethylbenzidine protocol to reveal retrogradely labeled neurons. Labeled neurons were found in a large set of nuclei within the rostral medulla and the pons. The greatest numbers of labeled neurons were in the vestibular complex and the nucleus prepositus hypoglossi. There were neurons labeled bilaterally throughout all the vestibular nuclei except the lateral vestibular nucleus, but most of the labeled neurons were in the caudal parts of the medial and inferior vestibular nuclei and in the central part of the superior vestibular nucleus; the nucleus prepositus was also labeled bilaterally, primarily caudally. Modest numbers of labeled neurons were found in the y-group, most ipsilaterally, and many neurons were labeled in the interstitial nucleus of the vestibular nerve. No labeled neurons were found in the vestibular ganglion following a large injection into the flocculus. A second large source of afferents to the flocculus was the medial, paramedial, and raphe reticular formation. Dense aggregates of labeled neurons were located in several pararaphe nuclei of the rostral medulla and the rostral pons and in the nucleus reticularis paramedianus of the medulla and several component nuclei of the nucleus reticularis tegmenti pontis bilaterally. Several groups of cells within and abutting upon the medial and rostral aspects of the abducens nucleus were labeled bilaterally. There was a modest projection from two parts of the pontine nuclei. Both a dorsal midline nucleus ventral to the nucleus reticularis tegmenti pontis and a collection of nuclei in a laminar region adjacent to the contralateral middle cerebellar peduncle contained labeled neurons whose numbers, while modest, were large compared to the projections to the flocculus in other animals. This generic difference may be due to the greater development of the smooth pursuit system in monkeys and the consequent need for a more substantial input from the cerebral cortex. As in other genera, the inferior olive projected to the flocculus via the dorsal cap of Kooy and the contiguous ventrolateral outgrowth. The projection was completely crossed and large injections labeled virtually every neuron in the dorsal cap, suggesting that the dorsal cap is the principal source of climbing fiber afferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomical connections of the primate pretectal nucleus of the optic tract.

The pretectal nucleus of the optic tract (NOT) plays an essential role in optokinetic nystagmus, the reflexive movements of the eyes to motion of the entire visual scene. To determine how the NOT can influence structures that move the eyes, we injected it with lectin-conjugated horseradish peroxidase and characterized its afferent and efferent connections. The NOT sent its heaviest projection to the caudal half of the ipsilateral dorsal cap of Kooy in the inferior olive. The rostral dorsal cap was free of labeling. The NOT sent lighter, but consistent, projections to other visual and oculomotor-related areas including, from rostral to caudal, the ipsilateral pregeniculate nucleus, the contralateral NOT, the lateral and medial terminal nuclei of the accessory optic system bilaterally, the ipsilateral dorsolateral pontine nucleus, the ipsilateral nucleus prepositus hypoglossi, and the ipsilateral medial vestibular nucleus. The NOT received input from the contralateral NOT, the lateral terminal nuclei bilaterally, and the ipsilateral pregeniculate nucleus. Although our injections involved the pretectal olivary nucleus (PON), there was neither orthograde nor retrograde labeling in the contralateral PON. Our results indicate that the NOT can influence brainstem preoculomotor pathways both directly through the medial vestibular nucleus and nucleus prepositus hypoglossi and indirectly through both climbing and mossy fiber pathways to the cerebellar flocculus. In addition, the NOT communicates strongly with other retino-recipient zones, whose neurons are driven by either horizontal (contralateral NOT) or vertical (medial and lateral terminal nuclei) fullfield image motion.

The origin of efferent pathways from the primary visual cortex, area 17, of the macaque monkey as shown by retrograde transport of horseradish peroxidase.

The retrograde transport of horseradish peroxidase has been used to identify efferent cells in area 17 of the macaque. Cells projecting to the lateral geniculate nucleus are small to medium sized pyramidal neurons with somata in lamina 6 and the adjacent white matter. The projection to the parvocellular division arises preferentially from the upper half of lamina 6, while that to the magnocellular division arises preferentially from the lower part of the lamina. The projection to both superior colliculus and inferior pulvinar arises from all sizes of pyramidal neurons lying in lamina 58 (Lund and Boothe, '75); at least pyramidal neurons of lamina 5B send collateral axon branches to both destinations. Injections with extensive spread of horseradish peroxidase show that many cells of lamina 4B and the large pyramidal neurons of upper lamina 6 also project extrinsically but their terminal sites have not been identified. Other studies have indicated that cells of laminae 2 and 3 project to areas 18 and 19. Therefore every lamina of the visual cortex, with the exception of those receiving a direct thalamic input, contains cells projecting extrinsically. Further, each lamina projects to a different destination and from Golgi studies can be shown to contain cells with specific patterns of dendritic branching which relate to the distribution of thalamic afferents and to the patterns of intracortical connections. These findings emphasise the significance of the horizontal organisation of the cortex with relation to the flow of information through it and contrast with the current concept of columnar organisation shown in physiological studies.

Monkey retinal ganglion cells: morphometric analysis and tracing of axonal projections, with a consideration of the peroxidase technique.

This paper presents evidence on the retinal distribution and central projections of retinal ganglion cells of various cell body sizes in the adult macaque monkey. The ganglion cell sizes have been determined by computer assisted measurement of camera lucida drawings at various eccentricities of both flat mounted and sectioned retinae. The pattern of projections of individual ganglion cells to the dorsal lateral geniculate nucleus and superior colliculus has been studied using retrograde axonal transport of horseradish peroxidase. Following peroxidase injections into the parvocellular laminae of the geniculate, virtually every ganglion cell was labeled within a circumscribed zone of the retina known to project to the region of the geniculate immediately surrounding the injection needle tip. After magnocellular injections, only the largest cells of the peripheral retina and approximately 26% of the ganglion cells of the parafovea were labeled. Peroxidase injections into the superior colliculus produced labeling of scattered ganglion cells of all sizes in the retina, although no labeled cells were found within the centralmost 10 degrees eccentricity. From these observations it is concluded that all ganglion cells of the macaque retina project to the parvocellular layers of the dorsal lateral geniculate, but that only the largest ganglion cells of the more peripheral retina and not all cells of the parafovea project to the magnocellular laminae. In contrast, only scattered ganglion cells, although these are of all sizes, appear to project to the superior colliculus. Two major problems with the peroxidase tracing technique are described: 1. The extent of stainable peroxidase activity around the injection site appears to be larger than the area of injected tracer actually available for uptake by axons to produce labeled cells. 2. Cut or damaged axons appear to incorporate peroxidase sufficiently to produce labeling of the cell body.

Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase.

To fulfill its putative role in short- and long-term modification of the vestibulo-ocular reflex, the flocculus of the cerebellum must send efferents to brainstem nuclei involved in the control of eye movements. In order to reveal the sites of these interactions, we determined the projections of the flocculus by autoradiography and orthograde transport of horseradish peroxidase in five rhesus macaques. Anterogradely labeled axons collected at the base of the injected folia and coursed caudally and medially between the middle cerebellar peduncle and the flocculus. They swept medially over the caudal surface of the middle cerebellar peduncle, over the dorsal surface of the cochlear nuclei, and then caudally along the lateral surface of the inferior cerebellar peduncle to pass over its dorsal surface in the cerebellopontine angle and terminate exclusively in the ipsilateral vestibular nuclei. Three contingents of axons could be differentiated. The axons of one group flowed caudally and medially into the y-group, which clearly received the densest floccular projection. Other, notably thicker, axons of this group continued rostrally and medially to terminate chiefly in the large-cell core of the superior vestibular nucleus. A second large contingent of thin axons streamed caudal and ventral to the y-group to form a compact tract adjacent to the lateral angle of the fourth ventricle and dorsal to the medial vestibular nucleus. Fibers from this tract (the angular bundle of Löwy) supplied a sizable projection to the rostral part of the medial vestibular nucleus and modest projection to the ventrolateral vestibular nucleus. A final group of fibers extended caudally and medially from the y-group in a plexus ventral to the dentate and interposed nuclei to terminate in the basal interstitial nucleus of the cerebellum (Langer, '85), a broadly distributed cerebellar nucleus on the roof of the fourth ventricle. The flocculus can affect vestibulo-ocular behavior only through these efferents to the vestibular nuclei and the basal interstitial nucleus of the cerebellum.

Decrease in saccadic performance after many visually guided saccadic eye movements in monkeys.

PURPOSE: To investigate the influence of repeated saccades and of background illumination on the metrics and dynamics of visually guided targeting saccades. METHODS: Eye movements were measured by magnetic search coil technique in seven trained monkeys (Macaca mulatta) while they performed many visually guided saccades in the dark or in dim background light. RESULTS: After 2000 to 7000 saccades in the dark, peak eye velocity on the average decreased by 20%, saccadic gain decreased slightly by 4.5%, and saccadic latency increased by 15%. All parameters also showed increased variability. In contrast, when testing was done in dim light, there was little to no change in average saccadic metrics and latency. CONCLUSIONS: The changes in saccadic metrics and dynamics in the dark do not reflect a change of the ocular plant but may reflect a change in the cortical or cerebellar influences on the brain stem burst generator linked to the monkeys attentional state. Background light mostly prevents this change.

Cerebellar influences on saccade plasticity.

Inaccurate saccades adapt to become more accurate. In this experiment the role of cerebellar output to the oculomotor system in adapting saccade size was investigated. We measured saccade adaptation after temporary inactivation of saccade-related neurons in the caudal part of the fastigial nucleus which projects to the oculomotor brain stem. We located caudal fastigial nucleus neurons with single unit recording and injected 0.1% muscimol among them. Two monkeys received bilateral injections and two monkeys unilateral injections. Unilateral injections made ipsiversive saccades hypermetric (gains >1.5) and contraversive saccades hypometric (gains approximately 0.6). Bilateral injections made both leftward and rightward saccades hypermetric (gains >1.5). During unilateral inactivation neither ipsiversive nor contraversive saccade size adapted after approximately 1,000 saccades. During bilateral inactivation, adaptation was either small or very slow. Most intact monkeys completely adapt after approximately 1,000 saccades to similar dysmetrias produced by intrasaccadic target displacement. After the monkeys receiving bilateral injections made >1,000 saccades in each horizontal direction, we placed them in the dark so that the muscimol dissipated without the monkeys receiving visual feedback about its saccade gain. After the dark period, 20-degree saccades were adapted to be 12% smaller, and 4-degree saccades to be 7% smaller. We expect this difference in adaptation because during caudal fastigial nucleus inactivation, monkeys made many large overshooting saccades and few small overshooting saccades. We conclude from these results that: (1) caudal fastigial nucleus activity is important in adapting dysmetric saccades; and (2) bilateral caudal fastigial nucleus inactivation impairs the relay of adapted signals to the oculomotor system, but it does not stop all adaptation from occurring.

Connections of cat omnipause neurons.

Omnipause neurons (OPNs) are brainstem neurons that have been implicated in the generation of saccades. Anatomically demonstrated projections from the OPN region to the cerebellum and spinal cord originate from neighboring neurons, not from OPNs. OPNs are activated following stimulation of the optic chiasm and superior colliculus, but not following stimulation of the vestibular nerve.

Saccadic eye movement deficits in the MPTP monkey model of Parkinson's disease.

Saccadic eye tracking was studied in a monkey given i.v. injections of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The Parkinson-like symptoms which appeared in the animal's general motor behavior (akinesia, bradykinesia, hypokinesia) were also observed in its eye tracking. Similar oculomotor deficits are seen in patients with idiopathic Parkinsonism. The MPTP model offers excellent possibilities for studying the mechanisms underlying the motor disabilities of Parkinson's disease.

Development of conjugate human eye movements.

Early studies of the development of oculomotor control in human infants relied on descriptions of eye movements. Recently, studies have been carried out using eye movement recording techniques typically used with adults. This review first considers the limitations of such techniques, especially as they are used with human infants, and then discusses the results of recent studies of human oculomotor development.

Infant eye movements: quantification of the vestibulo-ocular reflex and visual-vestibular interactions.

The gain of the infant vestibulo-ocular reflex (VOR) was determined when infants were rotated either in total darkness or while they viewed visual targets consisting of a stationary spot or a full field of black and white stripes. The average VOR gain in the dark was 1.03 +/- 0.014 for 1-4-month-old infants and 0.59 +/- 0.03 for adult subjects tested with appropriate controls for psychological "set". Longitudinal studies showed no significant change in gain over the first 4 months of life. Although the presence of the spot or full-field striped background increased adult compensatory gains from 0.59 to 1.0, the same visual targets had no effect on infant gains. Thus, an infant's VOR gain of nearly 1.0 apparently reduces reliance on the poorly developed smooth pursuit and optokinetic systems that, in adults, help the VOR provide perfect ocular stabilization.

Obtaining a quantitative measure of eye movements in human infants: a method of calibrating the electrooculogram.

We have developed a calibration procedure that combines the measurement of the EOG voltage with the concurrent assessment of the actual direction of gaze as revealed by the corneal reflection of a target light. Using this method, we have been able to calibrate the eye-position signal recorded from 2- and 3-month-old infants. Our results show that in young infants (1) the EOG is linearly related to eye position to at least +/- 20 deg; (2) the slopes of the calibration lines measured early and late in the same test session were not significantly different at the 0.1 level; (3) at the most eccentric eye position, the calibration was accurate to within +/- 1 deg; and (4) an abbreviated calibration at 0 and +/- 15 deg, which took less than 2 min, produced essentially the same slope (t-test not significant at the 0.1 level) as a longer procedure that tested at every 5 deg between +20 and -20 deg.

Smooth pursuit in 1- to 4-month-old human infants.

The ability of human infants < or = 4 months of age to pursue objects smoothly with their eyes was assessed by presenting small target spots moving with hold-ramp-hold trajectories at ramp velocities of 4-32 deg/sec. Infants as young as 1 month old followed such target motions with a combination of smooth-pursuit and saccadic eye movements interrupted occasionally by periods when the eyes remained stationary. The slowest targets produced variable performance, but targets moving 8-32 deg/sec produced consistent pursuit behavior, even in the youngest infants. By the fourth month, eye-movement latency decreased and smooth-pursuit gain and the percentage of smooth pursuit per trial increased for all target velocities, though these measures had not yet reached adult levels.