Anatomy and physiology of the primate interstitial nucleus of Cajal. II. Discharge pattern of single efferent fibers.

Anatomy and physiology of the primate interstitial nucleus of Cajal. II. Discharge pattern of single efferent fibers. J. Neurophysiol. 80: 3100-3111, 1998. Single efferent fibers of the interstitial nucleus of Cajal (NIC) were characterized physiologically and injected with biocytin in alert behaving monkeys. Quantitative analysis demonstrated that their discharge encodes a constellation of oculomotor variables. Tonic and phasic signals were related to vertical (up or down) eye position and saccades, respectively. Depending on how they encoded eye position, saccade velocity, saccade size, saccade duration, and smooth-pursuit eye velocity, fibers were characterized as regular or irregular, bi- or unidirectionally modulated, more or less sensitive, and reliable or unreliable. Further, fibers that did not burst for saccades (tonic) and fibers the eye-position and saccade-related signals of which increased in the same (in-phase) or in the opposite (anti-phase) directions were encountered. A continuum of discharge properties was the rule. We conclude that NIC efferent fibers send a combination of eye-position, saccade-, and smooth-pursuit-related signals, mixed in proportions that differ for different fibers, to targets of the vertical neural integrator such as extraocular motoneurons.

Comparison of two methods of producing adaptation of saccade size and implications for the site of plasticity.

Saccade accuracy is known to be maintained by adaptive mechanisms that progressively reduce any visual error that consistently exists at the end of saccades. Experimentally, the visual error is induced using one of two paradigms. In the first, the horizontal and medial recti of trained monkeys are tenectomized and allowed to reattach so that both muscles are paretic. After patching the unoperated eye and forcing the monkey to use the "paretic eye," saccades initially undershoot the intended target, but gradually increase in size until they almost acquire the target in one step. In the second, the target of a saccade is displaced in midsaccade so that the saccade cannot land on target. Again saccade size adapts until the target can be acquired in one step. Because adaptation with the latter paradigm is very rapid but adaptation using the former is slow, it has frequently been questioned whether or not the two forms of adaptation depend on the same neural mechanisms. We show that the rate of adaptation in both paradigms depends on the number of possible visual targets, so that when this variable is equated, adaptation occurs at similar rates in both paradigms. To demonstrate further similarities between the result of the two paradigms, an experiment using intrasaccadic displacements was conducted to show that rapid adaptation possesses the capacity to produce gain changes that vary with orbital position. The relative size of intrasaccadic displacements were graded with orbital position so as to mimic the position-dependent dysmetria initially produced by a single paretic extraocular muscle. Induced changes in saccade size paralleled the size of the displacements, being largest for saccades into one hemifield and being negligible for saccades into the other hemifield or in the opposite direction. Collectively, the data remove the rational for asserting that adaptation produced by the two paradigms depends on separate neural mechanisms. We argue that adaptation produced by both paradigms depends on the cerebellum.

The microscopic anatomy and physiology of the mammalian saccadic system.

A central goal of the Neurosciences is to provide an account of how the brain works in terms of cell groups organised into pattern generating networks. This review focuses on the neural network that generates the rapid movements of the eyes that are called saccades. A brief description of the metrical and dynamical properties of saccades is provided first. Data obtained from lesion and electrical stimulation experiments are then described; these indicate that the relevant neural machinery spreads over at least 10 distinct cortical and subcortical regions of the brain. Each one of these regions harbors several distinct classes of saccade related cells (i.e. cells whose discharge encodes the metrical and often dynamical properties of saccades). The morphological and physiological properties of about 30 saccade related cell classes are described. To generate the signals they carry, and therefore saccades, distinct classes of cells influence each other in a non-random manner. Anatomical evidence is provided that indicates the existence of about 100 distinct connections established between saccade related neurons. The overall picture of the saccadic system that emerges from these studies is one of intricate complexity. In part this is due to the presence of at least 3, multiply interconnected negative feedback loops. Several computational models of the saccadic system have been proposed in an attempt to understand the functional significance of the simultaneous operation of these loops. An evaluation of these models demonstrates that besides providing a coherent summary of the data that concern it, successful models of the saccadic system generate realistic saccades (in precise quantitative psychophysical terms) when their elements are stimulated, produce abnormal saccades, reminiscent of those encountered in the clinic, when their elements are disabled, while their constituent units display realistic discharge patterns and are connected in a manner that respects anatomy.

Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. II. Pontine neurons.

1. The discharge patterns and axonal projections of saccadic long-lead burst neurons (LLBNs) with somata in the pontine reticular formation were studied in alert squirrel monkeys with the use of the method of intraaxonal recording and horseradish peroxidase injection. 2. The largest population of stained neurons were afferents to the cerebellum. They originated in the dorsomedial nucleus reticularis tegmenti pontis (NRTP) including its dorsal cell group (N = 5), the preabducens intrafascicular nucleus (N = 5), and the raphe pontis (N = 1). Axons of all neurons coursed under NRTP and entered brachium pontis without having synapsed in the brain stem. Three axons sent collaterals to the floccular lobe, but other more distant targets of these and the other cerebellar afferents could not be determined. Movement fields of these neurons were intermediate between vectorial and directional types. 3. Four neurons had their somata in nucleus reticularis pontis oralis and terminations in the brain stem reticular formation. Each neuron was different, but all terminated in the region containing excitatory burst neurons, and most terminated in the region containing inhibitory burst neurons. Other targets include nucleus reticularis pontis oralis and caudalis, NRTP, raphe interpositus, and the spinal cord. Discharge patterns included both vectorial and directional types. 4. Two reticulospinal neurons had large multipolar somata either just rostral or ventral to the abducens nucleus. These neurons also projected to the medullary reticular formation, caudal nucleus prepositus hypoglossi, and dorsal and ventral paramedian reticular nucleus. 5. The functional implications of the connections of these LLBNs and those reported in the companion paper are extensively discussed. The fact that the efferents of the superior colliculus target the regions containing medium-lead saccadic burst neurons confirms the role of the colliculus in saccade generation. However, the finding that many other neurons project to these regions and the finding that superior colliculus efferents project more heavily to areas containing reticulospinal neurons argue for a diminished role of the superior colliculus in saccade generation but an augmented role in head movement control.

Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. I. Descending projections from the mesencephalon.

1. The intra-axonal recording and horseradish peroxidase injection technique together with spontaneous eye movement monitoring has been employed in alert behaving monkeys to study the discharge pattern and axonal projections of mesencephalic saccade-related long-lead burst neurons (LLBNs). 2. Most of the recovered axons (N = 21) belonged to two classes of neurons. The majority (N = 13) were identified as efferents of the superior colliculus and had circumscribed movement fields typical of collicular saccade-related burst neurons. This discharge pattern, their responses to electrical stimulation of one or both superior colliculi, and their morphological appearance identified them as members of the T class of tectal efferent neurons. 3. Axons of these T cells deployed terminal fields within several saccade-related brain stem areas including the nucleus reticularis tegmenti pontis, which projects to the cerebellum; the nucleus reticularis pontis oralis and caudalis, which contains excitatory premotor burst neurons; the nucleus raphe interpositus, which contains omnipause neurons; the nucleus paragigantocellularis, which contains inhibitory premotor burst neurons, as well as other less differentiated parts of the brain stem reticular formation. 4. The other class of LLBNs (N = 4) had their somata in the medullary reticular formation just lateral to the interstitial nucleus of Cajal. They projected primarily to the raphe nuclei, the medullary reticular formation, and the paramedian reticular nucleus. Discharges were of the directional type with up ON directions (N = 3) and down ON directions (N = 1). 5. Other fibers, which project to pontine and medullary oculomotor structures but whose somata were not recovered (N = 4), illustrate that there are also other types of LLBNs that contribute to the generation and control of saccadic eye movements. 6. Our findings complement previous data about the axonal trajectories of T-type superior colliculus efferents. They also demonstrate the existence of LLBNs located in the mesencephalic reticular formation and their target areas in the brain stem. Implications of these findings for current concepts of oculomotor control are discussed.

Anatomy and physiology of the primate interstitial nucleus of Cajal I. efferent projections.

1. The efferent projections of the interstitial nucleus of Cajal (NIC) were studied in the squirrel monkey after iontophoretic injections of biocytin and Phaseolus Vulgaris leucoagglutinin into the NIC. To ensure the proper placement of the tracer, the same pipettes were used to extracellularly record the discharge pattern of NIC neurons. 2. Three projection systems of the NIC were distinguished: commissural (through the posterior commissure), descending, and ascending. 3. The posterior commissure system gave rise to dense terminal fields in the contralateral NIC, the oculomotor nucleus, and the trochlear nucleus. 4. The descending system of NIC projections deployed dense terminal fields in the ipsilateral gigantocellular reticular formation and the paramedian reticular formation of the pons, as well as in the ventromedial and commissural nuclei of the first two spinal cervical segments. It also gave rise to moderate or weak terminal fields in the vestibular complex, the nucleus prepositus hypoglossi, the inferior olive, and the magnocellular reticular formation, as well as cell groups scattered along the paramedian tracts in the pons and the pontine and medullary raphe. 5. The ascending system of NIC projections gave rise to dense terminal fields in the ipsilateral mesencephalic reticular formation and the zona incerta as well as moderate or weak terminal fields in the ipsilateral centromedian and parafascicular thalamic nuclei. It also provided dense bilateral labeling of the rostral interstitial nucleus of the medial longitudinal fasciculus and the fields of Forel, and moderate or weak bilateral labeling of the mediodorsal, central medial, and central lateral nuclei of the thalamus. 6. Models of saccade generation that rely on feedback from the velocity-to-position integrators and include the superior colliculus in their local feedback loop are contradicted because no fibers originating from the NIC traveled to the superior colliculus to deploy terminal fields. 7. Consistent with its morphological and functional diversity, these data indicate that the primate NIC sends signals to a multitude of targets implicated in the control of eye and head movements.

Physiological and behavioral identification of vestibular nucleus neurons mediating the horizontal vestibuloocular reflex in trained rhesus monkeys.

1. To describe in detail the secondary neurons of the horizontal vestibuloocular reflex (VOR), we recorded the extracellular activity of neurons in the rostral medial vestibular nucleus of alert, trained rhesus monkeys. On the basis of their activity during horizontal head and eye movements, neurons were divided into several different types. Position-vestibular-pause (PVP) units discharged in relation to head velocity, eye velocity, eye position, and ceased firing during some saccades. Eye and head velocity (EHV) units discharged in relation to eye velocity and head velocity in the same direction so that the two signals partially canceled during the VOR. Two cell types discharged in relation to eye position and velocity but not head velocity; other types discharged in relation to head velocity only. 2. The position in the neural path from the primary vestibular afferents to abducens motoneurons was examined for each type. Direct input from the vestibular nerve was indicated if the cell could be activated by shocks to the nerve at latencies less than or equal to 1.4 ms. A projection to abducens motoneurons was indicated if spike-triggered averaging of lateral rectus electromyographic (EMG) activity yielded responses with a sharp onset at monosynaptic latencies. 3. PVP neurons were the principal interneuron in the VOR "three-neuron arc." Eighty percent received primary afferent input, and 66% made excitatory connections with contralateral abducens motoneurons. Surprisingly few, approximately 11%, made inhibitory connections with ipsilateral abducens motoneurons. This imbalance in the ipsi- and contralateral projections was confirmed by measuring the EMG activity evoked by electrical microstimulation in regions where PVP neurons were located. 4. EHV neurons whose activity increased during contralaterally directed head or eye movements were also interneurons in the ipsilateral inhibitory pathway. Eighty-nine percent received ipsilateral primary afferent input, and 25% projected to ipsilateral abducens motoneurons. EHV neurons excited during ipsilateral movements received neither direct primary afferent input nor projected to either abducens nucleus. A small proportion of each of two other cell types having sensitivity to contralateral eye position made excitatory connections with contralateral abducens motoneurons. Other types rarely were activated from the eighth nerve or projected to the abducens nucleus. 5. The significance of the connections of VOR interneurons and the signals they convey is discussed for three situations: smooth pursuit of a moving target, suppression of the VOR, and the VOR itself. PVP neurons convey a signal with a ratio of eye position and velocity components that is inappropriate to drive motoneurons during pursuit or the VOR.(ABSTRACT TRUNCATED AT 400 WORDS)

Structure of the primate oculomotor burst generator. I. Medium-lead burst neurons with upward on-directions.

1. To investigate the structure of the primate burst generator for vertical saccades, we obtained intra-axonal records from vertical medium-lead burst neurons with upward on-directions (UMLBs) in alert, behaving squirrel monkeys, while monitoring their spontaneous eye movements. After physiological characterization, these UMLBs were injected with horseradish peroxidase. 2. UMLBs (n = 14) had no spontaneous activity and emitted bursts of action potentials that preceded rapid eye movements by approximately 6 ms. Parameters of the burst (duration and number of spikes) were highly correlated with parameters of the rapid eye movement (duration and amplitude of the upward displacement of the eyes). 3. The axons of six UMLBs projected to the oculomotor complex. Their somata (4 were recovered) were all in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Their axons traveled caudally in the medial longitudinal fasciculus (MLF) and ramified in the interstitial nucleus of Cajal (NIC) before entering the oculomotor nucleus. Five axons terminated bilaterally in the subdivisions innervating the superior rectus and inferior oblique muscles and therefore were presumed to be excitatory. One axon terminated in the ipsilateral inferior rectus and superior oblique subdivisions of the oculomotor complex and was presumed to be inhibitory. 4. Additionally, our data demonstrate that the nucleus of the posterior commissure (nPC) may also contain UMLBs. The axon of one such neuron crossed the midline within the posterior commissure and provided terminal fields to the contralateral nPC, riMLF, NIC, and the mesencephalic reticular formation but not to the oculomotor complex. 5. In conclusion, our data demonstrate that the rostral mesencephalon of the monkey contains neurons that have both the activity and the connections that are necessary either to provide motoneurons innervating extraocular muscles of both eyes with the pulse of activity they display during upward saccades or to inhibit their antagonists. Furthermore, our data demonstrate that some UMLBs are better suited for closing the feedback path of the local feedback loop rather than for providing direct input to extraocular motoneurons.

Structure of the primate oculomotor burst generator. II. Medium-lead burst neurons with downward on-directions.

1. To investigate the morphology and physiology of vertical medium-lead burst neurons with downward on-directions (DMLBs), we impaled midbrain axons and recorded their discharge patterns in relation to spontaneous saccades of alert, behaving squirrel monkeys. Selected axons were injected with horseradish peroxidase and morphologically characterized. 2. DMLBs emitted bursts of impulses that preceded rapid eye movements by approximately 5 ms. Parameters of the burst (duration and number of spikes) were highly correlated with parameters of the saccadic eye movement (duration and amplitude of the downward displacement of the eyes). 3. Somata of DMLBs were recovered in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF, n = 14), and in the interstitial nucleus of Cajal (NIC, n = 2). Fibers originating from riMLF DMLBs projected, usually ipsilaterally, to the NIC as well as in the inferior rectus and the superior oblique subdivisions of the oculomotor complex. The axons of NIC DMLBs projected to the ipsilateral riMLF, NIC, and the mesencephalic reticular formation but not to the oculomotor complex. 4. Our data demonstrate that some DMLBs can provide extraocular motoneurons of both eyes with the pulse of activity they display during downward saccades. In addition, such neurons can supply the NIC with one of the signals that this nucleus is thought to integrate to extract an estimate of the vertical eye position. Finally, our data demonstrate the existence of DMLBs that do not establish direct connections with oculomotoneurons.

A structural basis for Hering's law: projections to extraocular motoneurons.

Conjugate eye movements are executed through the concurrent activation of several muscles in both eyes. The neural mechanisms that underlie such synergistic muscle activations have been a matter of considerable experimentation and debate. In order to investigate this issue, the projections of a class of primate premotoneuronal cells were studied, namely, the vertical medium-lead burst neurons (VMLBs), which drive vertical rapid eye movements. Axons of upward VMLBs ramify bilaterally within motoneuron pools that supply the superior rectus and inferior oblique muscles of both eyes. Axons of downward VMLBs ramify ipsilaterally in the inferior rectus portion of the oculomotor nucleus and in the trochlear nucleus. Thus, VMLBs can drive vertical motoneuron pools of both eyes during conjugate vertical rapid eye movements; these data support Hering's law.

Fourier analysis of saccades in monkeys and humans.

1. By recording eye movements with the search coil technique and subjecting them to an accurate infinite Fourier transform algorithm, we describe the Fourier spectra of human and monkey saccades. In both species we find heretofore undescribed features consisting of a regular pattern of local minima in the power plot, which cannot be attributed to noise. The frequency of these minima is well correlated with saccade duration. 2. Computer simulation shows that if the pulse component of the saccade is considered to be rectangular, then the first of these minima (called M1) occurs at a frequency that is the reciprocal of the duration of the pulse. 3. Comparing the position of this component during individual monkey saccades with electrophysiological recordings of motoneurons during the same saccades leads to the conclusion that these minima are related to the burst components in ocular motoneuron discharges. Specifically, the reciprocals of the frequencies of these minima are correlated with the duration of the burst component in the motoneuron discharge. 4. In the Fourier spectra of human saccades, the relationship of the frequency of M1 to saccadic duration is a function similar to that in the monkey. This adds to the evidence that the human saccade also is driven by a pulse-step signal. 5. In both monkeys and humans, T1, the reciprocal of the frequency of M1, is shorter than both the saccade duration and the burst duration of individual motoneurons, even though neurophysiological studies in monkeys generally report the saccadic burst duration to be equal to the saccade duration. This probably arises because the saccadic pulse is not rectangular, with the extremes contributing very little energy to the Fourier spectrum. By further computer modeling we show these shape effects explicitly: as the rise- and falltime increase, making the pulse less rectangular, T1 becomes shorter; in addition, as the asymmetry of rise and fall increases, the depth of the minima is reduced. We conclude that T1 measures the "effective pulse" duration of the motoneuron. 6. There is a difference in the relationship of effective pulse duration to the saccade duration between short and long saccades. For saccades shorter than approximately 40 ms in the human and 50 ms in the monkey, the pulse width as measured by this technique varies little with saccade duration. For longer saccades, effective pulse width increases linearly with duration. We agree with others that for short saccades the pulse is both height- and width-modulated; but for longer saccades, height modulation saturates and only width modulation remains.(ABSTRACT TRUNCATED AT 400 WORDS)

Discharge patterns and recruitment order of identified motoneurons and internuclear neurons in the monkey abducens nucleus.

1. Single neurons in the abducens nucleus were recorded extracellularly in alert rhesus macaques trained to make a variety of eye movements. An abducens neurons was identified as a motoneuron (MN) if its action potentials triggered an averaged EMG potential in the lateral rectus muscle. Abducens internuclear neurons (INNs) that project to the oculomotor nucleus were identified by collision block of spontaneous with antidromic action potentials evoked with a stimulating electrode placed in the medial rectus subdivision of the contralateral oculomotor nucleus. 2. All abducens MNs and INNs had qualitatively similar discharge patterns consisting of a burst of spikes for lateral saccades and a steady firing whose rate increased with lateral eye position in excess of a certain threshold. 3. For both MNs and INNs the firing rates associated with different, constant eye positions could be described accurately by a straight line with slope, K (the eye position sensitivity in spikes.s-1.deg-1), and intercept, T (the eye position threshold for steady firing). For different MNs, K increased as T varied from more medial to more lateral values. In contrast, the majority of INNs already were active for values of T more medial than 20 degrees and showed little evidence of recruitment according to K. 4. During horizontal sinusoidal smooth-pursuit eye movements, both MNs and INNs exhibited a sinusoidal modulation in firing rate whose peak preceded eye position. From these firing rate patterns, the component of firing rate related to eye velocity, R (the eye velocity sensitivity in spikes.s-1.deg-1.s-1), was determined. The R for INNs was, on average, 78% larger than that for MNs. Furthermore, R increased with T for MNs, whereas INNs showed no evidence of recruitment according to R. If, as in the cat, the INNs of monkeys provide the major input to medial rectus MNs and if simian medial rectus MNs behave like our abducens MNs, then recruitment order, which is absent in INNs, must be established at the MN pool itself. 5. Unexpectedly, the R of MNs decreased with the frequency of the smooth-pursuit movement. Furthermore, the eye position sensitivity, K, obtained during steady fixations was usually less than that determined during smooth pursuit. Therefore, conclusions about the roles of MNs and premotor neurons based on how their R and K values differ must be viewed with caution if the data have been obtained under different tracking conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Characteristics and functional identification of saccadic inhibitory burst neurons in the alert monkey.

1. With the use of single-unit recording, the reticular formation immediately caudal to the abducens nucleus was searched for saccadic burst neurons in alert, trained rhesus monkeys. We recorded 80 short- and long-lead burst neurons, investigated their connections, and quantitatively analyzed their discharge characteristics. 2. Like excitatory burst neurons located rostral to the abducens, these caudal burst neurons fire optimally for ipsilaterally directed saccades, fire less for vertical saccades, and fire minimally, if at all, for contralateral saccades. The direction associated with the maximum number of spikes was approximately along the horizontal axis (1 +/- 12 degrees (SD); n = 33). 3. The first spike of the burst led the saccade by 2-120 ms, depending on the unit. Neurons were divided into short lead (45%) and long lead (55%) using a burst-lead criterion of 15 ms. In the on-direction, the discharges of both types exhibited strong correlations between number of spikes in the burst and size of the horizontal saccade component; duration of the burst and duration of the saccade; and peak frequency of the burst and peak velocity of the saccade. These relations were looser for long-lead neurons than for short-lead neurons. 4. Horseradish peroxidase injected into the abducens nucleus retrogradely labeled cells in the contralateral reticular formation where burst neurons were recorded, showing that cells in this region make crossed monosynaptic connections. There was good agreement between the limits of this region, as determined physiologically and anatomically. 5. Microstimulation at the locus of recorded burst neurons elicited EMG potentials in the contralateral lateral rectus muscle of the appropriate sign and latency for a monosynaptic inhibitory projection to abducens motoneurons. Stimulation also elicited eye movements consistent with inhibition of the contralateral lateral rectus. 6. It is argued that these characteristics make it likely that the short-lead neurons are the source of the afference which generate the pause in contralateral abducens motoneuron firing during adducting saccades. These neurons are therefore analogous to the inhibitory burst neurons (IBNs) found in the cat. The characteristics of long-lead burst neurons, particularly their lead, make them less likely to subserve this function. These cells might be better suited to providing input to omnipause neurons or to the short-lead IBNs.

A new local feedback model of the saccadic burst generator.

1. To accommodate the finding that the superior colliculus is an important input to the brain stem pathways that generate saccades (the saccadic burst generator), a new model of the burst generator is proposed. Unlike the model of Robinson (61) from which it was derived, the model attempts to match a neural replica of change in eye position, which is the output of the burst generator, to a neural replica of change in target position, which is the output of the colliculus and the input to the model. 2. The elements of the model correspond to neurons known or thought to be associated with the actual primate saccadic burst generator and are mostly connected together in accord with the results of anatomical and physiological experiments. 3. The model was simulated on a digital computer to compare its behavior with that of the actual burst generator under normal and experimental conditions. Simulated peak burst frequency and saccade duration matched that obtained from monkey excitatory burst neurons and inhibitory burst neurons for saccades up to 15 degrees but did not match at larger sizes; stimulation of the omnipause neurons caused an interruption of the saccade, and the saccade resumed at the end of stimulation as in actual data; the model can generate the abnormally long-duration saccades seen under decreased alertness or various pathologies by changing the burst generator inputs and without having to change any properties of the neurons themselves or their connections; a simulated horizontal and vertical burst generator pair connected only through the omnipause neurons can generate realistic oblique saccades. 4. The implications of the model for higher-order control of the saccadic burst generator are discussed.

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)

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)

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.

Neuron activity in monkey vestibular nuclei during vertical vestibular stimulation and eye movements.

To elucidate how information is processed in the vestibuloocular reflex (VOR) pathways subserving vertical eye movements, extracellular single-unit recordings were obtained from the vestibular nuclei of alert monkeys trained to track a visual target with their eyes while undergoing sinusoidal pitch oscillations (0.2-1.0 Hz). Units with activity related to vertical vestibular stimulation and/or eye movements were classified as either vestibular units (n = 53), vestibular plus eye-position units (n = 30), pursuit units (n = 10), or miscellaneous units (n = 5), which had various combinations of head- and eye-movement sensitivities. Vestibular units discharged in relation to head rotation, but not to smooth eye movements. On average, these units fired approximately in phase with head velocity; however, a broad range of phase shifts was observed. The activities of 8% of the vestibular units were related to saccades. Vestibular plus eye-position units fired in relation to head velocity and eye position and, in addition, usually to eye velocity. Their discharge rates increased for eye and head movements in opposite directions. During combined head and eye movements, the modulation in unit activity was not significantly different from the sum of the modulations during each alone. For saccades, the unit firing rate either decreased to zero or was unaffected. Pursuit units discharged in relation to eye position, eye velocity, or both, but not to head movements alone. For saccades, unit activity usually either paused or was unaffected. The eye-movement-related activities of the vestibular plus eye-position and pursuit units were not significantly different. A quantitative comparison of their firing patterns suggests that vestibular, vestibular plus eye-position, and pursuit neurons in the vestibular nucleus could provide mossy fiber inputs to the flocculus. In addition, the vertical vestibular plus eye-position neurons have discharge patterns similar to those of fibers recorded rostrally in the medial longitudinal fasciculus. Therefore, our data support the view that vertical vestibular plus eye-position neurons are interneurons of the VOR.