Long-term size-increasing adaptation of saccades in macaques.

Motor learning adjusts movement size and direction to keep movements accurate. A useful model of motor learning, saccade adaptation, uses intra-saccade target movement to make saccades seem inaccurate and elicit adaptive changes in saccades. In the most studied saccade adaptation procedure, which we call short-term saccade adaptation (STSA), monkeys decrease or increase the size of their saccades by tracking 1000-2000 adapting target movements in a single saccade session. STSA elicits rapid changes of limited size and duration. Larger, more persistent reduction in saccade size results from adapting saccades daily for 19 days, a procedure that we call long-term saccade adaptation (LTSA). LTSA mimics the demands of rehabilitation more closely than does STSA and, unlike STSA, produces changes that could maintain long-term accuracy. Previous work describes LTSA that reduces saccade size in monkeys. Though convenient to study, size-decreasing LTSA is not a good model for rehabilitation because few injuries necessitate making movements smaller. Here we characterize size-increasing LTSA and compare it, in the same monkeys, to size-reducing LTSA. We found that size-increasing LTSA can double saccade gain in ∼21 days, and is slower than size-decreasing LTSA. In contrast to a single size-decreasing STSA, a single size-increasing STSA does not prevent additional saccade size increase at the normal rate when a monkey continues to track adapting target movements. We conclude that size-increasing LTSA is slower than size-decreasing LTSA but can make larger changes in saccade size. Size-increasing and size-decreasing LTSA use distinct mechanisms with different performance characteristics.

Purkinje cell axon collaterals terminate on Cat-301+ neurons in Macaca monkey cerebellum.

The monoclonal antibody Cat-301 identifies perineuronal nets around specific neuronal types, including those in the cerebellum. This report finds in adult Macaca monkey that basket cells in the deep molecular layer; granule cell layer (GCL) interneurons including Lugaro cells; large neurons in the foliar white matter (WM); and deep cerebellar nuclei (DCN) neurons contain subsets of Cat-301 positive (+) cells. Most Cat-301+ GCL interneurons are glycine+ and all are densely innervated by a meshwork of calbindin+/glutamic acid decarboxylase+ Purkinje cell collaterals and their synapses. DCN and WM Cat-301+ neurons also receive a similar but less dense innervation. Due to the heavy labeling of adjacent Purkinje cell dendrites, the innervation of Cat-301+ basket cells was less certain. These findings suggest that several complex feedback circuits from Purkinje cell to cerebellar interneurons exist in primate cerebellum whose function needs to be investigated. Cat-301 labeling begins postnatally in WM and DCN, but remains sparse until at least 3 months of age. Because the appearance of perineuronal nets is associated with maturation of synaptic circuits, this suggests that the Purkinje cell feedback circuits develop for some time after birth.

Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density of 120 cells/linear mm. Their morphology indicates that they include Golgi and Lugaro cell types with the majority containing both glycine and GABA or glutamic acid decarboxylase. These data are consistent with the proposal that, as in the rat cerebellum, these granular cell layer interneurons corelease glycine and GABA in the primate cerebellum. The patterns of labeling for glycine and GABA within Golgi and Lugaro cells also indicate that there are biochemical sub-types which are morphologically similar. Further, we find that glycine, GABA and glutamic acid decarboxylase identified candelabrum cells adjacent to the Purkinje cells which is the first time that this interneuron has been reported in primate cerebellar cortex. We propose that candelabrum cells, like the majority of Golgi and Lugaro cells, release both glycine and GABA.

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.

Projection of the magnocellular red nucleus to the region of the accessory abducens nucleus in the rabbit.

The projection of the magnocellular red nucleus (RNm) to the region of the accessory abducens nucleus (AABD) was traced in rabbit using the bidirectional tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP). In one set of animals, recordings of antidromic responses from RNm neurons elicited by electrical stimulation of the rubrospinal tract were used to localize injections of WGA-HRP for orthograde labeling of RNm terminals. In a different set of animals, horseradish peroxidase was injected into the retractor bulbi muscle to retrogradely label motoneurons of the AABD. The positions of RNm fibers and terminals were examined and compared to the locations and distribution of AABD cell bodies and labeled dendrites. Analyses revealed that along the entire rostrocaudal extent of the AABD, RNm efferents terminate primarily lateral to, or in the lateral aspects of, labeled motoneurons. For the rostral AABD, RNm efferents terminate only lateral to the nucleus. Although the terminals are not positioned to contact cell bodies of the AABD, they could overlap with dendrites that extend in the lateral direction. RNm efferents terminate more extensively within the posterior AABD, overlapping within both dendritic and cell body regions of the nucleus. Even in this posterior region, however, RNm efferents were distributed primarily over the lateral half of the nucleus. These data show that RNm can monosynaptically influence the AABD, through primarily its lateral and posterior aspects. Our findings also show that a major target of RNm efferents is the reticular cell population located lateral to the AABD, suggesting that the RNm also may affect AABD motoneuronal output indirectly through its projection to reticular cells.

Visual error is the stimulus for saccade gain adaptation.

Saccade accuracy is fundamental to clear vision. The brain maintains saccade accuracy by altering commands for saccades that are consistently inaccurate. For example, saccades that consistently overshoot their targets gradually become smaller. The signal that drives the adaptation of saccade size is not well understood. Previous reports propose that corrective movements and visual errors, both generated after inaccurate saccades, could be responsible for a change in saccade size. Here we show that we can elicit normal reductions in saccade size while eliciting few or no correction saccades. These normal reductions in saccade size indicate that visual errors, not correction saccades, drive the adaptation of saccades.

The role of the cerebellum in voluntary eye movements.

In general the cerebellum is crucial for the control but not the initiation of movement. Voluntary eye movements are particularly useful for investigating the specific mechanisms underlying cerebellar control because they are precise and their brain-stem circuitry is already well understood. Here we describe single-unit and inactivation data showing that the posterior vermis and the caudal fastigial nucleus, to which it projects, provide a signal during horizontal saccades to make them fast, accurate, and consistent. The caudal fastigial nucleus also is necessary for the recovery of saccadic accuracy after actual or simulated neural or muscular damage causes horizontal saccades to be dysmetric. Saccade-related activity in the interpositus nucleus is related to vertical saccades. Both the caudal fastigial nucleus and the flocculus/paraflocculus are necessary for the normal smooth eye movements that pursue a small moving spot. By using eye movements, we have begun to uncover basic principles that give us insight into how the cerebellum may control movement in general.

Role of the cerebellar posterior interpositus nucleus in saccades I. Effect of temporary lesions.

The ventrolateral corner of the cerebellar posterior interpositus nucleus (VPIN) contains many neurons that respond during saccades. To characterize the VPIN contribution to saccades, I located this area in three monkeys with single-unit recording and injected the GABA(A) agonist muscimol among saccade-related neurons there to reduce or eliminate neural activity. I compared the size, direction, velocity, and duration of saccades recorded before and after a unilateral injection in all three monkeys. In two of three monkeys, I also examined saccades after bilateral injection. After unilateral VPIN inactivation, upward saccades were abnormally large (avg. across all 3 monkeys = 112% of normal) and downward saccades were abnormally small (avg. across all 3 monkeys = 94% of normal). In the two monkeys tested, bilateral inactivation increased these abnormalities. Upward saccades went from 111% of normal size in these two monkeys after unilateral inactivation to 120% after bilateral inactivation; downward saccades went from 97 to 86%. VPIN inactivation caused changes in saccade gain and did not add of a constant offset to saccades. (The 1 exception was upward saccades in 1 monkey in which both gain and offset changed.) Neither uni- nor bilateral VPIN inactivation consistently affected the size of horizontal saccades (uni- avg. = 101% normal; bi- avg. = 97% normal). In two of the three monkeys, saccades to horizontal targets angled significantly upward after VPIN inactivation (uni- avg. = 3.6 degrees above normal, bi- avg. = 10.3 degrees above normal). The velocities of horizontal saccades were not strongly affected, but downward saccades exhibited abnormally low peak velocities and long durations. Upward velocities were inconsistently changed. I interpret these results to mean that the activity of some VPIN neurons helps drive the eyes downward and the activity of others helps drive the eyes upward. The downward drive outweighs the upward drive. The net effect of VPIN inactivation is to deprive all saccades of a downward component and to slow downward saccades.

Comparison of hepatic lesions in veal calves with concentrations of copper, iron and zinc in liver and kidney.

Veal calf producers in Indiana have reported condemnation of carcasses due to icterus as well as condemnation of livers because of yellow discoloration, hepatomegaly and fibrosis. This study assessed the degree of hepatic injury in affected veal calves and correlated it with copper, iron and zinc concentrations in the liver and kidney. Tissues examined histopathologically were from slaughtered and necropsied veal calves. Hepatic lesions were divided into histopathologic categories of severity (minimal, moderate, marked or severe) based upon the degree of fibrosis, biliary epithelial hyperplasia, and inflammation. Hepatic copper levels decreased as the severity of lesions increased. The clinical observations and morphologic changes suggested initial hepatic damage before 9 w-of-age. The affected calves either died of acute copper toxicosis or survived to develop hepatomegaly, hepatic discoloration and/or fibrosis at the time of slaughter.

Distribution of effective synaptic currents in cat triceps surae motoneurons. VI. Contralateral pyramidal tract.

We measured the effective synaptic currents (IN) produced by stimulating the contralateral pyramidal tract (PT) in triceps surae motoneurons of the cat. This is an oligosynaptic pathway in the cat that generates both excitation and inhibition in hindlimb motoneurons. We also determined the effect of the PT synaptic input on the discharge rate of some of the motoneurons by inducing repetitive firing with long, injected current pulses during which the PT stimulation was repeated. At resting potential, all but one triceps motoneuron received a net depolarizing effective synaptic current from the PT stimulation. The effective synaptic currents (IN) were much larger in putative type F motoneurons than in putative type S motoneurons [+4.6 +/- 2.9 (SD) nA for type F vs. 0.9 +/- 2.4 nA for putative type S]. When the values of IN at the threshold for repetitive firing were estimated, the distribution was markedly altered. More than 60% of the putative type S motoneurons received a net hyperpolarizing effective synaptic current from the pyramidal tract stimulation as did 33% of the putative type F motoneurons. This distribution pattern is very similar to that observed previously for the effective synaptic currents produced by stimulating the contralateral red nucleus. As would be expected from the wide range of IN values at threshold (-4.8 to +8.7 nA), the PT stimulation produced dramatically different effects on the discharge of different triceps motoneurons. The discharge rates of those motoneurons that received depolarizing effective synaptic currents at threshold were accelerated by PT stimulation (+1 to +8 imp/s), whereas the discharge rates of cells that received hyperpolarizing currents were retarded by the PT input (-2 to -7 imp/s). The change in firing rates produced by the PT stimulation was generally approximated by the product of the effective synaptic currents and the slopes of the motoneurons' frequency-current relations. Our findings indicate that the contralateral pyramidal tract may provide a powerful source of synaptic drive to some high-threshold motoneurons while concurrently inhibiting low-threshold cells. Thus this input system, like that from the contralateral red nucleus, can potentially alter the gain of the input-output function of the motoneuron pool as well as disrupt the normal hierarchy of recruitment thresholds.

Participation of caudal fastigial nucleus in smooth pursuit eye movements. II. Effects of muscimol inactivation.

We studied the effect of temporarily inactivating the caudal fastigial nucleus (CFN) in three rhesus macaques trained to make smooth pursuit eye movements. We injected the gamma-aminobutyric acid A agonist muscimol into one or both CFNs where we had recorded pursuit-related neurons a few minutes earlier. Inactivating the CFN on one side impaired pursuit in one monkey so severely that it could not follow step-ramp targets moving at 20 degrees/s, the target velocity that we used to test the other two monkeys. We tested this monkey with targets moving at 10 degrees/s. In all three monkeys, unilateral CFN inactivation either increased the acceleration of ipsilateral step-ramp pursuit (in 2 monkeys, to 144 and 220% of normal) or decreased the acceleration of contralateral pursuit (in 1 monkey, to 71% of normal). Muscimol injected into both CFNs in two of the monkeys left both ipsilateral and contralateral acceleration nearly normal in both monkeys (101% of normal). Unilateral CFN inactivation also impaired the velocity of maintained pursuit as the monkeys tracked a target moving at a constant velocity or oscillating sinusoidally. Averaged across both types of movements in all three monkeys, gains for ipsilateral, contralateral, upward, and downward pursuit were 94, 67, 84, and 73% of normal, respectively. Unilateral CFN inactivation also impaired the monkeys' ability to suppress their vestibuloocular reflex (VOR). Averaged across the two monkeys VOR gain during suppression increased from 0.06 to 0.25 during yaw rotation and from 0.21 to 0.59 during pitch rotation. Bilateral CFN inactivation reduced pursuit gains in all directions more than unilateral injection did. In the two monkeys tested, ipsilateral, contralateral, upward, and downward gains went from 94, 86, 85, and 74% of normal, respectively, after we inactivated one CFN to 88, 73, 80, and 64% of normal after we also inactivated the second CFN. We can explain many, but not all, of the effects of CFN activation on smooth pursuit with the behavior of CFN neurons, and the assumption that the activity of each CFN neuron helps drive pursuit movements in the direction that best activates that neuron. We conclude that the CFN, like the flocculus-ventral paraflocculus, is a cerebellar region involved in control of smooth pursuit.

Characteristics of saccadic gain adaptation in rhesus macaques.

We adapted the saccadic gain (saccadic amplitude/target step amplitude) by requiring monkeys to track a small spot that stepped to one side by 5, 10, or 15 degrees and then, during the initial targeting saccade, jumped either forward or backward by a fixed percentage of the initial step. Saccadic gain increased or decreased, respectively, as a function of the number of adapting saccades made in that direction. The relation between gain and the number of adapting saccades was fit with an exponential function, yielding an asymptotic gain and a rate constant (the number of saccades to achieve 63% of the total change in gain). Backward intrasaccadic target jumps of 15, 30, and 50% of the initial target step reduced the asymptotic gain by an average of 12.2, 23.1, and 36.4%, respectively, with average rate constants of 163, 368, and 827 saccades, respectively. During 50% backward jumps, some saccades, especially those to larger target steps, became slower and lasted longer. Forward intrasaccadic jumps of 30% increased the asymptotic gain by 23.3% (average rate constant of 1,178 saccades). After we had caused adaptation, we induced recovery of gain toward normal by requiring the animal to track target steps without intrasaccadic jumps. Recovery following forward adaptation required about one third fewer saccades than the preceding gain increase. Recovery following backward adaptation required about the same average number of saccades as the preceding gain decrease. The first saccades of recovery were slightly less adapted than the last saccades of adaptation, suggesting that a small part of adaptation might have been strategic. After 50% backward jumps had reduced saccadic gain, the hypometric primary saccades during recovery were followed by hypometric corrective saccades, suggesting that they too had been adapted. When saccades of only one size underwent gain reduction, saccades to target steps of other amplitudes showed much less adaptation. Also, saccades in the direction opposite to that adapted were not adapted. Gain reductions endured if an adapted animal was placed in complete darkness for 20 h. These data indicate that saccadic gain adaptation is relatively specific to the adapted step and does not produce parametric changes of all saccades. Furthermore, adaptation is not a strategy, but involves enduring neuronal reorganization in the brain. We suggest that this paradigm engages mechanisms that determine saccadic gain in real life and therefore offers a reversible means to study their neuronal substrate.

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.

Role of the cerebellum in movement control and adaptation.

Three recent discoveries have substantially improved our knowledge of cerebellar function. First, the forelimb regions of the interpositus nuclei specialize in control of one particular limb movement, reach to grasp. Second, a new model indicates that vestibulo-ocular reflex adaptation requires neural changes in both the cerebellum and the brainstem. Finally, the caudal fastigial nucleus uses both short- and long-term influences to maintain saccade accuracy.

Effect of dietary retinyl palmitate on the promotion of altered hepatic foci by 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl in rats initiated with diethylnitrosamine.

The purpose of this study was to determine the effects of dietary vitamin A on the tumor promoting effect of 3,3',4,4'-TCB and 2,2',4,4',5,5'-HCB in a two-stage rat hepatocarcinogenesis model with diethylnitrosamine (DEN, 150 mg/kg) as the initiator. Two weeks after DEN injection rats were fed a purified diet containing either 2000 or 100,000 IU of vitamin A in the form of retinyl palmitate. Rats received four biweekly injections of 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB (300 mumol/kg), or both (150 mumol/kg each) in corn oil (10 ml/kg) for 8 weeks. Control animals received vehicle only. Six rats in each group that received no DEN treatment were used as additional control animals. Ten days after the last injection the rats were killed. In rats fed the low retinyl palmitate diet, treatment with 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB or both compounds lowered hepatic retinyl palmitate content. This effect was prevented by high dietary retinyl palmitate supplementation in rats treated with 2,2',4,4',5,5'-HCB, but not 3,3',4,4'-TCB or both compounds together. Histopathological examination of the liver showed that high dietary retinyl palmitate lessened the severity of hepatocellular necrosis and fatty changes induced by 3,3',4,4'-TCB alone or in combination with 2,2',4,4',5,5'-HCB. The latter did not cause significant pathological lesions to the liver. However, high dietary retinyl palmitate was not able to prevent thymic involution caused by 3,3',4,4'-TCB. The number and volume of altered hepatic foci were increased by 2,2',4,4',5,5'-HCB and particularly 3,3',4,4'-TCB; no synergistic effect was seen. Supplementation with high dietary retinyl palmitate diminished the number and volume of foci. These results show that supplementation with high dietary retinyl palmitate protects against hepatocellular necrosis, fatty changes, and preneoplastic changes induced by 3,3',4,4'-TCB as well as against preneoplastic changes induced by 2,2',4,4',5,5'-HCB. In addition, these two agents did not synergistically induce preneoplastic changes in DEN-induced rats.

Distribution of vestibulospinal synaptic input to cat triceps surae motoneurons.

We applied supramaximal, repetitive stimulation to the lateral vestibular nucleus (Deiters' nucleus, DN) at 200 Hz to evoke stead-state synaptic potentials in ipsilateral triceps surae motoneurons of the cat. The effective synaptic currents underlying these potentials were measured using a modified voltage-clamp technique. The steady-state effective synaptic currents evoked by activating DN were generally small and depolarizing (mean 2.5 +/- 2.6 nA). DN stimulation generated hyperpolarizing synaptic currents in 2 of the 34 triceps motoneurons studied. The effective synaptic currents from DN tended to be larger in putative type F motoneurons than in putative type S cells (type F mean 3.0 +/- 3.1 nA; type S mean 1.8 +/- 1.0 nA). There was a statistically significant difference between the inputs to putative type FF and putative type S motoneurons (mean difference 2.8 nA, t = 2.87, P < 0.01). The synaptic input from DN to medial gastrocnemius motoneurons had approximately the same amplitude as that from homonymous Ia afferent fibers. However, the distribution of DN input with respect to putative motor unit type was the opposite of that previously reported for Ia afferent input. Thus, the synaptic input from DN might act to compress the range of recruitment thresholds within the motoneuron pool and thereby increase the gain of its input-output function.

Participation of the caudal fastigial nucleus in smooth-pursuit eye movements. I. Neuronal activity.

1. We recorded single-unit activity from neurons of an output of the cerebellum, the fastigial nucleus, in two rhesus macaques while the monkeys tracked small moving targets with their eyes. Many neurons in the caudal part of the fastigial nucleus exhibited a modulation in their discharge rates when smooth-pursuit eye movements were elicited by either sinusoidal or step-ramp motions of a small target. 2. The pursuit direction that elicited the most vigorous modulation in unit firing to sinusoidal target motion could be horizontal, vertical, or oblique. Most often, the preferred direction was in the contralateral and/or downward direction (50 of 69 neurons) or in the ipsilateral and/or upward direction (13 of 69). 3. For units whose preferred smooth-pursuit directions were either contralateral/downward or ipsilateral/upward during sinusoidal pursuit, peak firing as measured by the phase shift of periodic modulation at 0.5-0.8 Hz occurred near the time of peak velocity. The discharge of 80% of the neurons with contralateral/downward preferred directions preceded eye velocity by an average of -27 degrees; thus these neurons discharged maximally during eye acceleration. In contrast, neurons with ipsilateral/upward preferred directions lagged peak velocity by an average of +10.5 degrees and therefore discharged during eye deceleration. 4. The average eye velocity sensitivity for sinusoidal pursuit between 0.5 and 0.8 Hz was 0.83 +/- 0.57 (SD) spikes/s per degrees/s. We also tested 36 units during pursuit at a variety of frequencies in their preferred directions and found that firing rates increased monotonically with peak eye velocity. However, the firing rate saturated at velocities ranging from 20 to 60 degrees/s for different units. 5. When a monkey tracked a step-ramp target motion, three discharge patterns emerged in the 27 units tested. Just over half of the units discharged a burst of spikes that preceded (average lead of 27.4 +/- 17 ms) and lasted throughout the initial third of the eye acceleration; the burst was followed by a subsequent steady firing that continued after the eye had accelerated to its steady velocity. Fewer neurons discharged a burst that began late in the acceleration and was followed by steady firing. Occasional neurons showed only a gradual increase in firing rate during acceleration followed by a steady discharge. 6. Thirty of the 31 fastigial smooth-pursuit units tested also were modulated during sinusoidal yaw and/or pitch oscillations while the animals fixated a spot that rotated with them.(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.