Brainstem Circuits Triggering Saccades and Fixation.

Omnipause neurons (OPNs) in the nucleus raphe interpositus have tonic activity while the eyes are stationary ("fixation") but stop firing immediately before and during saccades. To locate the source of suppression, we analyzed synaptic inputs from the rostral and caudal superior colliculi (SCs) to OPNs by using intracellular recording and staining, and investigated pathways transmitting the inputs in anesthetized cats of both sexes. Electrophysiologically or morphologically identified OPNs received monosynaptic excitation from the rostral SCs with contralateral dominance, and received disynaptic inhibition from the caudal SCs with ipsilateral dominance. Cutting the tectoreticular tract transversely between the contralateral OPN and inhibitory burst neuron (IBN) regions eliminated inhibition from the caudal SCs, but not excitation from the rostral SCs in OPNs. In contrast, a midline section between IBN regions eliminated disynaptic inhibition in OPNs from the caudal SCs but did not affect the monosynaptic excitation from the rostral SCs. Stimulation of the contralateral IBN region evoked monosynaptic inhibition in OPNs, which was facilitated by preconditioning SC stimulation. Three-dimensional reconstruction of HRP-stained cells revealed that individual OPNs have axons that terminate in the opposite IBN area, while individual IBNs have axon collaterals to the opposite OPN area. These results show that there are differences in the neural circuit from the rostral and caudal SCs to the brainstem premotor circuitry and that IBNs suppress OPNs immediately before and during saccades. Thus, the IBNs, which are activated by caudal SC saccade neurons, shut down OPN firing and help to trigger saccades and suppress ("latch") OPN activity during saccades.SIGNIFICANCE STATEMENT Saccades are the fastest eye movements to redirect gaze to an object of interest and bring its image on the fovea for fixation. Burst neurons (BNs) and omnipause neurons (OPNs) which behave reciprocally in the brainstem, are important for saccade generation and fixation. This study investigated unsolved important questions about where these neurons receive command signals and how they interact for initiating saccades from visual fixation. The results show that the rostral superior colliculi (SCs) excite OPNs monosynaptically for fixation, whereas the caudal SCs monosynaptically excite inhibitory BNs, which then directly inhibit OPNs for the initiation of saccades. This inhibition from the caudal SCs may account for the omnipause behavior of OPNs for initiation and maintenance of saccades in all directions.

Neural Circuits of Inputs and Outputs of the Cerebellar Cortex and Nuclei.

This article is dedicated to the memory of Masao Ito. Masao Ito made numerous important contributions revealing the function of the cerebellum in motor control. His pioneering contributions to cerebellar physiology began with his discovery of inhibition and disinhibition of target neurons by cerebellar Purkinje cells, and his discovery of the presence of long-term depression in parallel fiber-Purkinje cell synapses. Purkinje cells formed the nodal point of Masao Ito's landmark model of motor control by the cerebellum. These discoveries became the basis for his ideas regarding the flocculus hypothesis, the adaptive motor control system, and motor learning by the cerebellum, inspiring many new experiments to test his hypotheses. This article will trace the achievements of Ito and colleagues in analyzing the neural circuits of the input-output organization of the cerebellar cortex and nuclei, particularly with respect to motor control. The article will discuss some of the important issues that have been solved and also those that remain to be solved for our understanding of motor control by the cerebellum.

Brainstem neural circuits for fixation and generation of saccadic eye movements.

We review neural connections of the superior colliculus (SC) and brainstem saccade-related neurons in relation to saccade generation mechanism. The caudal and rostral SC play a role in saccade generation and visual fixation, respectively. This functional differentiation suggests that different connections should exist between these two SC areas and their brainstem target neurons. We examined synaptic potentials evoked by stimulation of the rostral and caudal SC in inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in anesthetized cats. The caudal and rostral SC produced monosynaptic excitation and disynaptic inhibition in IBNs, respectively. Intracellular HRP staining showed that single IBNs sent their axons to abducens motoneurons, IBNs and OPNs on the opposite side. OPNs received monosynaptic excitation from the rostral SC, and disynaptic inhibition from the caudal SC via opposite IBNs. These neural connections are discussed in relation to the saccade triggering system and the model proposed by Miura and Optican.

The entire trajectories of single pontocerebellar axons and their lobular and longitudinal terminal distribution patterns in multiple aldolase C-positive compartments of the rat cerebellar cortex.

The mammalian cerebellar cortex is compartmentalized, both anatomically and histochemically, into multiple parasagittal bands. To characterize the multiple zonal patterns of pontocerebellar mossy fiber projection, single neurons in the basilar pontine nucleus (BPN) were labeled by injecting biotinylated dextran amine into the BPN, and the entire axonal trajectory of single labeled neurons (n = 25) was reconstructed in relation to aldolase C compartments of Purkinje cells in rats. Single pontocerebellar axons, after passing through the contralateral middle cerebellar peduncle, ran transversely in the deep cerebellar white matter toward and often across the midline, and on their ways, gave rise to 2-10 primary collaterals at almost right angles in specific lobules only contralaterally or bilaterally with contralateral predominance. Each primary collateral further branched in a parasagittal plane to form a strip-shaped longitudinal termination zone with rosette-type swellings clustered in aldolase C-positive compartments in a single or multiple lobules, mainly in compartment 4+//5+, 5+//6+, and 6+//7+. Axons arising from the central, rostral, and lateral part of the BPN projected with multiple branches, mainly to simple lobule, crus II and paramedian lobule, to crus I and dorsal paraflocculus, and to ventral paraflocculus and lobule IXc, respectively. The results showed the pontocerebellar projection is closely related to lobular and compartmental organization of the cerebellum. A comparison of single axon morphologies of different mossy fiber systems indicates that the projection pattern of single pontocerebellar neurons with multiple collaterals innervating different longitudinal compartments arranged in a mediolateral direction represents a general feature of mossy fiber projection.

Brain Stem Neural Circuits of Horizontal and Vertical Saccade Systems and their Frame of Reference.

Sensory signals for eye movements (visual and vestibular) are initially coded in different frames of reference but finally translated into common coordinates, and share the same final common pathway, namely the same population of extraocular motoneurons. From clinical studies in humans and lesion studies in animals, it is generally accepted that voluntary saccadic eye movements are organized in horizontal and vertical Cartesian coordinates. However, this issue is not settled yet, because neural circuits for vertical saccades remain unidentified. We recently determined brainstem neural circuits from the superior colliculus to ocular motoneurons for horizontal and vertical saccades with combined electrophysiological and neuroanatomical techniques. Comparing well-known vestibuloocular pathways with our findings of commissural excitation and inhibition between both superior colliculi, we proposed that the saccade system uses the same frame of reference as the vestibuloocular system, common semicircular canal coordinate. This proposal is mainly based on marked similarities (1) between output neural circuitry from one superior colliculus to extraocular motoneurons and that from a respective canal to its innervating extraocular motoneurons, (2) of patterns of commissural reciprocal inhibitions between upward saccade system on one side and downward system on the other, and between anterior canal system on one side and posterior canal system on the other, and (3) between the neural circuits of saccade and quick phase of vestibular nystagmus sharing brainstem burst neurons. In support of the proposal, commissural excitation of the superior colliculi may help to maintain Listing's law in saccades in spite of using semicircular canal coordinate.

Convergent synaptic inputs from the caudal fastigial nucleus and the superior colliculus onto pontine and pontomedullary reticulospinal neurons.

The caudal fastigial nucleus (FN) is known to be related to the control of eye movements and projects mainly to the contralateral reticular nuclei where excitatory and inhibitory burst neurons for saccades exist [the caudal portion of the nucleus reticularis pontis caudalis (NRPc), and the rostral portion of the nucleus reticularis gigantocellularis (NRG) respectively]. However, the exact reticular neurons targeted by caudal fastigioreticular cells remain unknown. We tried to determine the target reticular neurons of the caudal FN and superior colliculus (SC) by recording intracellular potentials from neurons in the NRPc and NRG of anesthetized cats. Neurons in the rostral NRG received bilateral, monosynaptic excitation from the caudal FNs, with contralateral predominance. They also received strong monosynaptic excitation from the rostral and caudal contralateral SC, and disynaptic excitation from the rostral ipsilateral SC. These reticular neurons with caudal fastigial monosynaptic excitation were not activated antidromically from the contralateral abducens nucleus, but most of them were reticulospinal neurons (RSNs) that were activated antidromically from the cervical cord. RSNs in the caudal NRPc received very weak monosynaptic excitation from only the contralateral caudal FN, and received either monosynaptic excitation only from the contralateral caudal SC, or monosynaptic and disynaptic excitation from the contralateral caudal and ipsilateral rostral SC, respectively. These results suggest that the caudal FN helps to control also head movements via RSNs targeted by the SC, and these RSNs with SC topographic input play different functional roles in head movements.

Digital morphometry of rat cerebellar climbing fibers reveals distinct branch and bouton types.

Cerebellar climbing fibers (CFs) provide powerful excitatory input to Purkinje cells (PCs), which represent the sole output of the cerebellar cortex. Recent discoveries suggest that CFs have information-rich signaling properties important for cerebellar function, beyond eliciting the well known all-or-none PC complex spike. CF morphology has not been quantitatively analyzed at the same level of detail as its biophysical properties. Because morphology can greatly influence function, including the capacity for information processing, it is important to understand CF branching structure in detail, as well as its variability across and within arbors. We have digitally reconstructed 68 rat CFs labeled using biotinylated dextran amine injected into the inferior olive and comprehensively quantified their morphology. CF structure was considerably diverse even within the same anatomical regions. Distinctly identifiable primary, tendril, and distal branches could be operationally differentiated by the relative size of the subtrees at their initial bifurcations. Additionally, primary branches were more directed toward the cortical surface and had fewer and less pronounced synaptic boutons, suggesting they prioritize efficient and reliable signal propagation. Tendril and distal branches were spatially segregated and bouton dense, indicating specialization in signal transmission. Furthermore, CFs systematically targeted molecular layer interneuron cell bodies, especially at terminal boutons, potentially instantiating feedforward inhibition on PCs. This study offers the most detailed and comprehensive characterization of CF morphology to date. The reconstruction files and metadata are publicly distributed at NeuroMorpho.org.

Neural substrate for suppression of omnipause neurons at the onset of saccades.

The saccade trigger signal was proposed by D.A. Robinson, but neural substrates for triggering saccades by inhibiting omnipause neuron (OPN) activity still remain controversial. We investigated tectal inputs to OPNs by recording intracellular potentials from OPNs and inhibitory burst neurons (IBNs) and searched for interneurons to inhibit OPNs in the brainstem of anesthetized cats. IBNs received monosynaptic excitation from the contralateral caudal superior colliculus (SC) and disynaptic inhibition via contralateral IBNs from the ipsilateral caudal SC, whereas IBNs received disynaptic inhibition from the rostral SC. The latter disynaptic inhibition was mediated by OPNs, since OPNs received monosynaptic excitation from the rostral SC and projected to IBNs. In contrast, OPNs received disynaptic inhibition from the caudal SC. This disynaptic inhibition from the caudal SC was mediated to OPNs by IBNs. These findings suggested possible roles of IBNs for triggering and maintaining saccades by actively inhibiting the tonic activity of OPNs.

Suppression of smooth pursuit eye movements induced by electrical stimulation of the monkey frontal eye field.

This study was performed to characterize the properties of the suppression of smooth pursuit eye movement induced by electrical stimulation of the frontal eye field (FEF) in trained monkeys. At the stimulation sites tested, we first determined the threshold for generating electrically evoked saccades (Esacs). We then examined the suppressive effects of stimulation on smooth pursuit at intensities that were below the threshold for eliciting Esacs. We observed that FEF stimulation induced a clear deceleration of pursuit at pursuit initiation and also during the maintenance of pursuit at subthreshold intensities. The suppression of pursuit occurred even in the absence of catch-up saccades during pursuit, indicating that suppression influenced pursuit per se. We mapped the FEF area that was associated with the suppressive effect of stimulation on pursuit. In a wide area in the FEF, suppressive effects were observed for ipsiversive, but not contraversive, pursuit. In contrast, we observed the bilateral suppression of both ipsiversive and contraversive pursuit in a localized area in the FEF. This area coincided with the area in which we have previously shown that stimulation suppressed the generation of saccades in bilateral directions and also where fixation neurons that discharged during fixation were concentrated. On the basis of these results, we compared the FEF suppression of pursuit with that of saccades with regard to several physiological properties and then discussed the role of the FEF in the suppression of both pursuit and saccades, and particularly in the maintenance of visual fixation.

Response properties of fixation neurons and their location in the frontal eye field in the monkey.

Electrical stimulation of the frontal eye field (FEF) has recently been reported to suppress the generation of saccades, which supports the idea that the FEF plays a role in maintaining attentive fixation. This study analyzed the activity of fixation neurons that discharged during fixation in the FEF in relation to visual fixation and saccades in trained monkeys. The neural activity of fixation neurons increased at the start of fixation and was maintained during fixation. When a fixation spot of light disappeared during steady fixation, different fixation neurons exhibited different categories of response, ranging from a decrease in activity to an increase in activity, indicating that there is a continuum of fixation neurons, from neurons with foveal visual-related activity to neurons with activity that is related to the motor act of fixating. Fixation neurons usually showed a decrease in their firing rate before the onset of visually guided saccades (Vsacs) and memory-guided saccades in any direction. The reduction in activity of fixation neurons nearly coincided with, or occurred slightly before, the increase in the activity of saccade-related movement neurons in the FEF in the same monkey. Although fixation neurons were scattered in the FEF, about two thirds of fixation neurons were concentrated in a localized area in the FEF at which electrical stimulation induced strong suppression of the initiation of Vsacs bilaterally. These results suggest that fixation neurons in the FEF are part of a suppression mechanism that could control the maintenance of fixation and the initiation of saccades.

Neural circuits for triggering saccades in the brainstem.

Here we review the functional anatomy of brainstem circuits important for triggering saccades. Whereas the rostral part of the superior colliculus (SC) is considered to be involved in visual fixation, the caudal part of the SC plays an important role in generation of saccades. We determined the neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and omnipause neurons (OPNs) in the nucleus raphe interpositus. To reveal the neural mechanisms of triggering saccadic eye movements, we analysed the effects of stimulation of the SC on intracellular potentials recorded from IBNs and OPNs in anaesthetized cats. Our studies show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC, via contralateral IBNs. Further, IBNs receive disynaptic inhibition from the rostral part of the SC, on either side, via OPNs. Intracellular recording revealed that OPNs receive excitation from the rostral parts of the bilateral SCs, and disynaptic inhibition from the caudal SC mainly via IBNs. The neural connections determined in this study are consistent with the notion that the "fixation zone" is localized in the rostral SC, and suggest that IBNs, which receive monosynaptic excitation from the caudal "saccade zone," may inhibit tonic activity of OPNs and thereby trigger saccades.

Molecular, topographic, and functional organization of the cerebellar nuclei: analysis by three-dimensional mapping of the olivonuclear projection and aldolase C labeling.

The olivocerebellar climbing fiber projection pattern is closely correlated with the pattern of aldolase C expression in cerebellar Purkinje cells. Based on this expression pattern, the olivocerebellar projection can be classified into five "groups" of functional compartments. Each group originates from a subarea within the inferior olive that projects to multiple cortical stripes of Purkinje cells, all of which are either aldolase C positive or aldolase C negative. However, no equivalent compartmental organization has been demonstrated in the cerebellar nuclei (CN). Thus, in the CN of the rat, we systematically mapped the location of olivonuclear projections belonging to the five groups and determined their relationship to the expression of aldolase C in Purkinje cell axonal terminals. The CN were divided into caudoventral aldolase C-positive and rostrodorsal aldolase C-negative parts. The olivonuclear terminations from the five groups projected topographically to five separate compartments within the CN that partly crossed the traditional boundaries that define the fastigial, interposed, and dentate nuclei. Each compartment had mostly uniform cytoarchitecture and the same aldolase C expression (either positive or negative) that was found in the corresponding olivocortical projection. These results suggest a new view of the organization of the CN whereby the pattern of olivonuclear terminations links portions of different CN together. We propose that each compartment in the CN, along with its corresponding olivary subarea and cortical stripes, may be related to a different aspect of motor control.

Neural organization of the pathways from the superior colliculus to trochlear motoneurons.

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1-2.3 and 1.1-3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

Long descending motor tract axons and their control of neck and axial muscles.

It has been tacitly assumed that a long descending motor tract axon consists of a private line connecting the cell of origin to a single muscle, as a motoneuron innervates a single muscle. However, this notion of a long descending motor tract referred to as a private line is no longer tenable, since recent studies have showed that axons of all major long descending motor tracts send their axon collaterals to multiple spinal segments, suggesting that they may exert simultaneous influences on different groups of spinal interneurons and motoneurons of multiple muscles. The long descending motor systems are divided into two groups, the medial and the lateral systems including interneurons and motoneurons. In this chapter, we focus mainly on the medial system (vestibulospinal, reticulospinal and tectospinal systems) in relation to movement control of the neck, describe the intraspinal morphologies of single long descending motor tract axons that are stained with intracellular injection of horseradish peroxidase, and provide evidence that single long motor-tract neurons are implicated in the neural implementation of functional synergies for head movements.

Synaptic inputs and their pathways from fixation and saccade zones of the superior colliculus to inhibitory burst neurons and pause neurons.

The caudal part of the superior colliculus (SC) plays an important role in the generation of saccades, whereas the rostral part of the SC is considered to be involved in visual fixation. The present study was performed to determine neural connections from the rostral and caudal parts of the SC to inhibitory burst neurons (IBNs) and pause neurons (PNs) in the nucleus raphe interpositus in the anesthetized cat, and to reveal the functional role of the rostral SC on eye movements. The intracellular potentials from IBNs and PNs were recorded, and the effects of stimulation of the SC on these neurons were analyzed. The results show that IBNs receive monosynaptic excitation from the contralateral caudal SC, and disynaptic inhibition from the ipsilateral caudal SC via contralateral IBNs. In addition, IBNs receive disynaptic inhibition from the rostral part of the SC on either side via inhibitory interneurons other than IBNs. Intracellular recording from PNs revealed that they receive convergent excitation from the rostral parts of the bilateral superior colliculi and that the rostral SC inhibits IBNs on both sides via PNs. The neural connections determined in this study support the functional independence of the rostral SC and are consistent with the notion that the "fixation zone" is localized in the rostral SC. These results show that the fixation zone in the rostral SC may suppress the initiation of bilateral saccades via pause neurons.

Initiation and suppression of saccades by the frontal eye field in the monkey.

After a saccadic eye movement occurs to an interesting object appearing in the visual field, visual fixation holds its image on the fovea and suppresses saccades to other objects appearing in the visual field. To understand the neural mechanism of visual fixation, the effects of electrical stimulation of the frontal eye field (FEF) on the generation of electrically evoked saccades (Esacs) and the suppression of saccades in trained monkeys were investigated. When the properties of the electrically evoked suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) were examined, two types of suppression were found. Stimulation of a wide area of the FEF suppressed only ipsiversive Vsacs and Msacs at stimulus intensities lower than those for eliciting Esacs, whereas stimulation of a localized area of the FEF suppressed the initiation of both Vsacs and Msacs in any direction during and approximately 50 ms after stimulation. However, neither stimulation affected the vector of these saccades. The thresholds for suppression were usually less than 50 microA. The most effective stimulation timing for the suppression of ipsiversive and contraversive Vsacs was approximately 40 to 50 ms before saccade onset. Therefore, suppression occurred in the efferent pathway for Vsacs at the premotor rather than the motoneuronal level, most likely in the superior colliculus and/or the paramedian pontine reticular formation. The results suggest that the suppression in the FEF may play a role in maintaining visual fixation by suppressing the generation of saccades.

Molecular, topographic, and functional organization of the cerebellar cortex: a study with combined aldolase C and olivocerebellar labeling.

Aldolase C (zebrin) expression in Purkinje cells reveals stripe-shaped compartments in the cerebellar cortex. However, it is not clear how these compartments are related to cerebellar functional localization. Therefore, we identified olivocerebellar projections to aldolase C compartments by labeling climbing fibers with biotinylated dextran injected into various small areas within the inferior olive in rats. Specific rostral and caudal aldolase C compartments were linked in an orderly manner by common olivocerebellar projection across the rostrocaudal boundary on lobule VIc-crus Ib. Based on the localization of the olivary origins of projection to similar compartments, the compartments and olivocerebellar projections could be sorted into five groups: group I, positive compartments extending from the posterior lobe to the anterior lobe innervated by the principal olive and some neighboring areas; group II, positive compartments localized within the posterior lobe innervated by several medial subnuclei; group III, vermal and central negative compartments innervated by the centrocaudal medial accessory olive; group IV, negative and lightly positive compartments in the hemisphere and the rostral and caudal pars intermedia innervated by the dorsal accessory olive and some neighboring areas; group V, the flocculus and nodulus. The olivocerebellar topography within each group was simple and suggests an "orientation axis" within the concerned parts of the inferior olive. Furthermore, parts of the inferior olive in each group receive specific afferent inputs, indicating a close relationship between aldolase C compartments and functional localization. Thus, the five-group scheme we propose here may integrate the molecular, topographic, and functional organization of the cerebellum.

Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. I. Suppression of ipsilateral saccades.

When a saccade occurs to an interesting object, visual fixation holds its image on the fovea and suppresses saccades to other objects. Electrical stimulation of the frontal eye field (FEF) has been reported to elicit saccades, and recently also to suppress saccades. This study was performed to characterize properties of the suppression of visually guided (Vsacs) and memory-guided saccades (Msacs) induced by electrical stimulation of the FEF in trained monkeys. For any given stimulation site, we determined the threshold for electrically evoked saccades (Esacs) at < or =50 microA and then examined suppressive effects of stimulation at the same site on Vsacs and Msacs. FEF stimulation suppressed the initiation of both Vsacs and Msacs during and about 50 ms after stimulation at stimulus intensities lower than those for eliciting Esacs, but did not affect the vector of these saccades. Suppression occurred for ipsiversive but not contraversive saccades, and more strongly for saccades with larger amplitudes and those with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for suppression was about 50 ms before saccade onset, which suggests that suppression occurred in the efferent pathway for generating Vsacs at the premotor rather than the motoneuronal level, most probably in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of ipsilateral saccades were distributed over the classical FEF where saccade-related movement neurons were observed. The results suggest that the FEF may play roles in not only generating contraversive saccades but also maintaining visual fixation by suppressing ipsiversive saccades.

Suppression of visually and memory-guided saccades induced by electrical stimulation of the monkey frontal eye field. II. Suppression of bilateral saccades.

To understand the neural mechanism of fixation, we investigated effects of electrical stimulation of the frontal eye field (FEF) and its vicinity on visually guided (Vsacs) and memory-guided saccades (Msacs) in trained monkeys and found that there were two types of suppression induced by the electrical stimulation: suppression of ipsilateral saccades and suppression of bilateral saccades. In this report, we characterized the properties of the suppression of bilateral Vsacs and Msacs. Stimulation of the bilateral suppression sites suppressed the initiation of both Vsacs and Msacs in all directions during and approximately 50 ms after stimulation but did not affect the vector of these saccades. The suppression was stronger for ipsiversive larger saccades and contraversive smaller saccades, and saccades with initial eye positions shifted more in the saccadic direction. The most effective stimulation timing for the suppression of ipsilateral and contralateral Vsacs was approximately 40-50 ms before saccade onset, indicating that the suppression occurred most likely in the superior colliculus and/or the paramedian pontine reticular formation. Suppression sites of bilateral saccades were located in the prearcuate gyrus facing the inferior arcuate sulcus where stimulation induced suppression at < or =40 microA but usually did not evoke any saccades at 80 microA and were different from those of ipsilateral saccades where stimulation evoked saccades at < or =50 microA. The bilateral suppression sites contained fixation neurons. The results suggest that fixation neurons in the bilateral suppression area of the FEF may play roles in maintaining fixation by suppressing saccades in all directions.

Functional compartmentalization in the flocculus and the ventral dentate and dorsal group y nuclei: an analysis of single olivocerebellar axonal morphology.

The cerebellar cortex consists of multiple longitudinal bands defined by their olivocerebellar projection. Single olivocerebellar axons project to a narrow longitudinal band in the cerebellar cortex and to the cerebellar nucleus with their axon collaterals. This olivocortical and olivonuclear organization is related to the functional compartmentalization of the cerebellar system. To reveal the detailed morphologic organization in the flocculus and the cerebellar and vestibular nuclei, we examined olivocerebellar projection by reconstructing the entire trajectories of 19 single olivofloccular axons and by anterograde mapping with biotinylated dextran in the rat. The flocculus was composed of 12 longitudinal band-shaped compartments that subdivided 5 previously described zones. These longitudinal bands were innervated differentially by the caudal and rostral portions of the dorsal cap (DC) and the ventrolateral outgrowth (VLO) and the rostral pole of the medial accessory olive. Single olivofloccular axons with an average of 5.1 climbing fibers usually projected to a single longitudinal band in the flocculus and to the ventral dentate or dorsal group y nucleus with their collaterals. DC neurons projected moderately to the rostrolateral portion of the ventral dentate nucleus, whereas VLO neurons projected densely to the medial portion of the ventral dentate nucleus and the dorsal group y nucleus with rostrocaudal topography. DC and VLO neurons did not project to the vestibular nuclei, although floccular Purkinje cells projected to the vestibular, ventral dentate, and dorsal group y nuclei. The fine morphologically identified longitudinal bands and topographic olivonuclear projections were correlated with previous electrophysiologically defined functional zones in the flocculus and inferior olive.