Lobule VII Research Articles

Cerebellovestibular projection from the posterior lobe cortex in the rabbit: an experimental study with the retrograde HRP method. I. Topographical relationships.

The sources of corticovestibular projections from the cerebellar posterior lobe vermis and hemisphere in the rabbit were investigated by the retrograde horseradish peroxidase (HRP) tracing method. Following iontophoretic injections into various subdivisions of the vestibular nuclear complex (VNC), labelled Purkinje neurones were identified ipsilaterally in all vermal lobules (VI through IX) and some regions of the hemisphere. The results indicate that projection is profuse and directed to all four nuclei of VNC. The labelling suggests some topographical relationships between lobules and especially sublobules of the posterior lobe and individual nuclei of VNC. The major projection originates from lobules VI and IX. A moderate projection derives from lobule VIII whereas that from lobule VII is small. Projections from the hemisphere arise mainly from crus I and crus II of the ansiform lobule. Those from the copula pyramidis, lobule HV and the ventral paraflocculus are sparse. In the present study a topographical relationships were more precisely established than before because the technique revealed VNC afferents from individual sublobules of the cerebellar posterior lobe cortex.

Transcranial magnetic stimulation over the posterior cerebellum during visually guided saccades in man.

Recent intensive neurophysiological experiments in the monkey have demonstrated the function of the cerebellum in the control of saccadic eye movements. Microstimulation studies on monkeys have determined that the cerebellar cortex, which is specifically involved in the control of saccades, is located in vermal lobules VIc and VII. The Purkinje-cell axons arising from this vermal area terminate almost exclusively in an ellipsoidal region which protrudes dorsocaudally from the fastigial nucleus. Saccade-related cells in the fastigial nucleus are located exclusively in the ellipsoidal region. Microstimulation of the vermis modulated the activity of saccade-related cells in the fastigial nucleus, and then produced dysmetric saccades. In this study, we investigated effects of cerebellar stimulation on saccade metrics in man using a transcranial magnetic stimulation (TMS) device. Focal TMS was applied over the posterior cerebellum at an area approximately 7 mm lateral and caudal to the inion during horizontal visually guided saccades in six normal subjects. The TMS device was triggered after the onset of saccades with a latency of 0, 20, 40 or 60 ms. We investigated the effect of TMS on the amplitude and velocity of saccadic eye movements. For visually guided saccades directed contralateral to the stimulation side, TMS of the posterior cerebellum with the latency of 0 ms produced hypometric saccades followed by corrective saccades. Transcranial magnetic stimulation with latencies of 20, 40 and 60 ms had no effect on saccade metrics. On the other hand, for ipsilateral saccades, TMS with latencies of 0, 20 and 40 ms produced hypermetric saccades followed by postsaccadic drift.(ABSTRACT TRUNCATED AT 250 WORDS)

Purkinje cell complex spike activity during voluntary motor learning: relationship to kinematics

1. We examined the relationship of cerebellar Purkinje cell discharge to the scaling of kinematics during a voluntary motor learning paradigm. The study focused on whether the occurrence of complex spike (CS) discharge was associated with kinematic changes. Two primates (Macaca mulatta) were trained to move a cursor using a two-joint manipulandum over a horizontal video screen from a start target to one of four target boxes. The relationship between the cursor and the hand (gain) was changed, requiring scaling of movement distance to complete the task. As previously described, when the novel gain was presented over 100-200 movement trials the animals adapted their movements by using a strategy of scaling the amplitude and velocity of the first phase of the movement while keeping time to peak velocity constant. 2. The paradigm consisted of four different phases. A control phase at a gain of 1.0 was initially performed. The learning phase over the next 180-210 movements used one of four gains (0.6, 0.75, 1.5, or 2.0). Last, a testing phase involved 80% of 100 trials at the learned gain and 20% of the trials at the control gain of 1.0. The distance control phase consisted of using a gain of 1.0 but having the animal move to targets placed at the distance and direction the hand moved in the adapted state. 3. Simple spikes (SSs) and CSs of 141 Purkinje cells recorded primarily in the intermediate and lateral regions of zones V and VI in three cerebellar hemispheres from the two primates were recorded during the distance control, control, learning, and testing phases. Some cells were recorded in lobule VII and Crus I. CS activity increased during the learning phase, as documented previously. The increase in CS discharge occurred before or during the first 200-300 ms of the movement. This is the same time period in which the kinematic changes necessary for adaptation to the novel gain occur. Of 141 Purkinje cells recorded during the learning paradigm, 104 (74%) demonstrated significant increases in CS firing rate during the learning-testing phase. Of these 104 cells, 82 had statistically significant SS modulation. 4. Movement trials with CSs were separated from the trials without CSs. Aligning the kinematic and spike train data on movement onset, the average velocity profiles were subtracted from each other and a strict statistical criterion applied to test for the significance of any differences. Movement trials randomly sorted into two groups served as a control.(ABSTRACT TRUNCATED AT 400 WORDS)

The pontocerebellar projection: longitudinal zonal distribution of fibers from discrete regions of the pontine nuclei to vermal and parafloccular cortices in the rat

A longitudinal parasagittal organization (alternating labeled and unlabeled stripes) of mossy fiber terminals in the paraflocculus and in the vermal lobule VII of the cerebellum was found after small injections (less than 50 nl) of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into discrete regions of the basilar pontine nuclei (BPN) of rats. Up to three stripes were found within the paraflocculus of both sides, following injections (of about 500 μm in diameter) in either the medial or lateral region of the caudal half of the BPN. Up to five stripes were found in the vermal lobule VII after similar size injections into the rostro-ventral region of the BPN. These results emphasize the possibility that the parasagittal zonal arrangement could be a common pattern of organization shared by climbing and mossy fiber afferents.

Enlargement of olivo-cerebellar microzones in the agranular cerebellum of adult rats

Previous work on normal adult rat showed that the vibrissae project, through the climbing fiber (CF) system, onto the Purkinje cells (PCs) of the contralateral cerebellar hemivermis of lobule VII. The highly elaborated CF projections from a given row of vibrissae delimit a narrow parasagittal zone which can be regarded as a functional olivo-cerebellar microzone. Interestingly, the adult one-to-one relationship between PCs and CFs is preceded by a transient phase during which each PC receives synaptic inputs from several CF collaterals which will be eliminated but one, when granule cells begin to establish synapses on PCs. Therefore, the question arose as to whether this synaptic elimination process could participate in the refinement of the topographical organization of CF projections and could contribute to the formation of such precise peripheral maps onto the cerebellum. In the present study, the topographical map of the CF-mediated projections of mystacial vibrissae onto the vermal PCs of lobule VII was determined in adult rats whose cerebellar PCs remain polyinnervated by olivary CFs due to degranulation by postnatal X-irradiation. Using intracellular recordings, we examined the responsiveness of PCs in lobule VII during mechanical stimulation of the 3rd row of contralateral vibrissae, and positioned cells responding to the stimulation on an averaged planar map of lobule VII. Comparison of the results to those obtained in our previous work on normal rats showed that the activated cells were more numerous and more diffusely distributed. PCs exhibiting the best characteristics of response were distributed evenly from the midline to 700 μm lateral in the contralateral hemivermis and not gathered in a parasagittal microzone centered on the plane 200 μm as in normal rats. These results strongly suggest that synaptic elimination in the olivo-cerebellar system participates in the segregation of CF-mediated inputs into functional microzones on the cerebellar cortex.

Abnormality of cerebellar vermian lobules VI and VII in patients with infantile autism: identification of hypoplastic and hyperplastic subgroups with MR imaging.

Infantile autism is a neurobehavioral disorder that is widely believed to have etiologically distinct subtypes, including subtypes with a genetic basis, but no neuroanatomic evidence firmly supports this belief. To date, only one type of cerebellar abnormality has been identified in patients with autism: hypoplasia of the vermis and hemispheres. By using a large sample of autistic patients and healthy volunteers along with precise MR imaging and quantitative procedures, we sought to replicate previous reports of cerebellar vermian hypoplasia in autism and to identify additional subtypes of cerebellar abnormality. Using MR technology, we imaged and measured posterior and anterior vermian regions in 50 autistic patients (2-40 years old) and 53 healthy control subjects (3-37 years old). The autistic patients had social, language, cognitive, behavioral, and medical history characteristics that were typical of the general autistic population. By using precise procedures for positioning and aligning MR slices, we obtained comparable MR images within and across subject groups. Statistical analyses showed two subgroups of autistic patients, one (86% of the patients) with findings consistent with vermian hypoplasia and another (12% of the patients) with evidence of vermian hyperplasia. The hypoplasia subgroup included 43 patients whose mean midsagittal area for vermian lobules VI and VII was 237 +/- 38 mm2, and the hyperplasia subgroup included six patients whose mean area was 377 +/- 12 mm2. Thus, the area of lobules VI and VII in the hypoplasia subgroup was 16% smaller than the mean area in the control subjects (282 +/- 42 mm2) (p < .0001), whereas that in the hyperplasia subgroup was 34% larger (p < .0001). Analyses showed that these two subtypes of vermian abnormalities were present across all ages of autistic patients studied. Two different subtypes of autistic patients can be identified on the basis of the presence of vermian hypoplasia or hyperplasia as seen on MR images. Possible origins for vermian hypoplasia include environmental trauma and genetic factors.

Topographic organization of rat locus coeruleus and dorsal raphe nuclei: distribution of cells projecting to visual system structures.

Previous reports from this laboratory and elsewhere have provided evidence that the locus coeruleus (LC) and dorsal raphe (DR) nuclei are topographically organized with respect to their efferent targets. Whereas most of these previous studies have focused on relationships between these monoamine-containing brainstem nuclei and cerebral cortex, basal ganglia, and limbic structures, they have not systematically examined the distribution of LC and DR cells that project to multiple structures with common sensory or motor functions. The goal of the present study was to characterize and compare the distributions of LC and DR cells which project to different visual areas of the rat central nervous system. Long-Evans hooded rats received unilateral pressure injections of the retrograde tracer wheat germ agglutinin-horseradish peroxidase in either the dorsal lateral geniculate, ventral lateral geniculate, or lateral posterior nucleus of thalamus; superior colliculus, cortical area 17, cortical area 18a/b; cerebellar vermis (lobules VI and VII); or paraflocculus. Transverse sections through the midbrain and pons were examined by light microscopy after performing routine tetramethyl benzidine histochemical procedures. For all cases studied, retrogradely labeled cells were observed throughout the rostrocaudal extent of the LC and DR; however, labeling patterns which were distinctive for different injection sites were noted in each of these brainstem nuclei. The major conclusion drawn from this work is that subsets of LC and DR cells which project to different target structures within the rat visual system are found in overlapping but not necessarily coextensive zones within these nuclei. These studies provide further evidence of a rough topographic ordering within both the LC and DR nuclei, as well as support a new hypothesis that the outputs from each of these nuclei are organized with respect to the sensory related functions of their efferent targets.

Climbing fiber representation of the renal afferent nerve in the vermal cortex of the cat cerebellum

In order to understand how the cerebellum may participate in various autonomic functions, it is necessary to first determine the occurrence and distribution of the various visceral inputs in the cerebellar cortex and their relation to other cerebellar afferents. This study examines the organization of climbing fiber responses (complex spikes) of Purkinje cells elicited by electrical stimulation of the renal afferent nerve and their relationship to climbing fiber responses representing the body surface. Visceral and somatic afferent responses were mapped in the lateral vermal cortex of lobules V to VII in chloralose-anesthetized cats. Extracellular single-unit recordings were made from 628 Purkinje cells, of which 14% had climbing fiber responses induced by renal afferent nerve stimulation. Except for one Purkinje cell, the renal climbing fiber input converged with somatic induced climbing fiber input. Tactile stimulation also elicited 54% of cells, which were unresponsive to the renal afferent nerve stimulation. The occurrence and distribution of the climbing fiber responses elicited by renal afferent nerve stimulation varied between lobules V, VI, and VII for the proportion of responsive units, the onset latencies, and topological organization. More renal responsive units were encountered in lobules V (18%) and VII (17%) than in lobule VI (6%), the average latency of renal climbing fiber responses was significantly longer in lobule VII than in lobules V and VI, and the latencies were also different among various parasagittal planes in lobules V and VII. The proportional representation of various body areas for cells with renal and somatic convergent input was different than for cells with only somatic representation. Proportionally, the forelimb had the greatest representation in lobule V, split receptive fields were frequently represented in lobule VI, and the face was well represented in lobule VII. The results of this study, in conjunction with studies showing climbing fiber representation of the vagal and splanchnic nerves, further substantiate role of the cerebellum in autonomic functions.

Role of the dorsolateral pontine nucleus in two components of optokinetic nystagmus (OKN).

The anatomical features of the dorsolateral pontine nucleus (DLPN) implicate a role of the nucleus in the generation of smooth-pursuit eye movements. The DLPN receives convergent inputs from a variety of parieto-occipital cortical visual areas and projects its fibers to the flocculus and vermal lobules VI and VII. In addition to cortical afferent fibers, the DLPN receives descending fibers from the nucleus of the optic tract which is indicated as the first subcortical optokinetic nystagmus (OKN) relay. DLPN units respond not only to a discrete visual spot but also to large-field OKN stimuli. On the basis of the above anatomical and physiological features, OKN was investigated in 2 alert monkeys whose DLPN was physiologically identified and into which reversible lidocaine was injected. The present findings showed that a rapid rise in OKN velocity was reduced in both monkeys, whose lesions included the uppermost rostral part of the nucleus in the one monkey and the entire nucleus in the other, whereas optokinetic after-nystagmus velocity was affected only in the latter. Taken together with physiological data, the DLPN possibly shares the domain of low selectivity speed selection in OKN and does not play a main role in the generation of OKN.

Burst discharges of mossy fibers in the oculomotor vermis of macaque monkeys during saccadic eye movements

Mossy fiber activity was recorded from the oculomotor vermis (lobules VIc and VII) during visually guided saccades. Saccade-related activities of 99 mossy fiber units were observed in two alert macaque monkeys. Ninety-six units were characterized by high-frequency bursts of firing in response to visually guided saccades (burst unit). These units were silent during all periods of fixation in any gaze position. Three units showed eye position-related tonic discharges with saccadic bursts. The lead time of saccadic bursts ranged from 2.6 to 80.5 ms (mean 27.9 ms, SD 16.6 ms). About 75% of the burst units exhibited a long lead burst characterized by a slow buildup, while the remaining units showed short lead bursts with a sharp onset. About 80% of the units showed burst in association with contralaterally directed saccades. The remaining units exhibited bursts in association with ipsilateral saccades. Preferred directions in this population covered the entire field including the vertical and the oblique. About 68% of long lead burst units exhibited the movement field which consists of a whole sector of the entire oculomotor range (directional type). About 32% of long lead burst units showed the movement field which is a closed area within the oculomotor range (vectorial type). On the other hand, peak frequency of short lead burst units increased in proportion to saccade amplitude. The end of the burst in all units always preceded the completion of saccade. The end of burst was time-locked to the completion of saccade, so that the lead time from the end of burst to the end of saccade was consistent among these units and, was constant regardless of saccadic amplitude. The duration between the peak and the offset of burst was correlated with the amplitude of saccade (0.63 ≦ r ≦ 0.83). Long lead burst of mossy fibers was almost comparable to burst activity in the nucleus reticularis tegmenti pontis (NRTP), while short lead burst of mossy fibers closely resembles activity of excitatory burst neurons in the paramedian pontine reticular formation (PPRF). These findings suggest that the cerebellum receives command signal from the superior colliculus via the NRTP and feedback signal from the PPRF.

Differential modulation of Purkinje cell activity by enkephalin and corticotropin releasing factor

Several peptides have been localized within afferents to the opossum's cerebellum, including cholecystokinin (15), enkephalin (16, 17) and corticotropin releasing factor (7, 9). Each of these peptides has a heterogeneous laminar and lobular distribution. Two peptides, enkephalin (ENK) and corticotropin releasing factor (CRF) are present in specific populations of climbing fibers and mossy fibers, which have an overlapping distribution in several areas of the cerebellum, in particular the lateral aspect of vermal lobules VII and VIII. Within this location ENK and CRF are co-localized in individual climbing fibers and mossy fibers (7). In the present study, the physiological effects of these peptides on Purkinje cell activity were analyzed. The data indicate that ENK and CRF have opposite effects on Purkinje cell activity. ENK suppresses spontaneous activity as well as that induced by application of glutamate and aspartate, as described previously (5). In contrast, CRF enhances both spontaneous and amino acid-induced unit activity. Further, when applied simultaneously, CRF blocks the suppressive effect induced by ENK. Previous studies have shown that climbing fibers, as well as the mossy fiber-parallel fiber pathway, are excitatory to Purkinje cells (11). However, immunohistochemical data have shown that these afferents are heterogeneous with respect to their chemical content (7–9, 15–17, 25). As found in the current and previous studies (3, 5) peptides in climbing and mossy fibers modulate the responsiveness of Purkinje cells to primary excitatory neurotransmitters in selected areas of the cerebellar cortex. However, the firing rate of individual Purkinje cells is differentially altered depending on which neurochemical messenger(s) are released. Thus, within circumscribed lobules of the cerebellum, activation of a climbing fiber or the mossy fiberparallel fiber pathway may not always result in a stereotypical excitation of their target neurons. The release of neuromodulators with the primary neurotransmitter may lead to a modification of the response. Thus, a wide range of responses following activation of a single afferent fiber is possible leading to synaptic plasticity in cerebellar circuitry.

The tectorecipient zone in the inferior olivary nucleus in the rat.

Tecto-olivary and olivocerebellar projections in the rat were investigated in order to identify the tectorecipient zone in the inferior olivary nucleus and to determine whether inferior olivary neurons projecting to the cerebellar tecto-olivo-recipient zones (lobule VII, crus II, lobulus simplex, and paramedian lobule) originate in the different regions within the tectorecipient zone. An electrophysiological method and an axonal transport technique of wheat-germ agglutinin-conjugated horseradish peroxidase were used. The tectorecipient zone was identified in the caudomedial region of the medial accessory olive. Neurons projecting to lobule VII originated in the caudomedial region of the tectorecipient zone, but those to crus II, lobulus simplex, and paramedian lobule originated in its rostrolateral region. These observations suggest that there are two independent tecto-olivo-cerebellar systems: 1) superior colliculus--the medial region of the tectorecipient zone--lobule VII--the caudomedial region of the fastigial nucleus; and 2) superior colliculus--the rostralateral region of the tectorecipient region--crus II, lobulus simplex, and paramedian lobule--the dorsolateral protuberance of the fastigial nucleus.

Magnetic resonance imaging in autism: measurement of the cerebellum, pons, and fourth ventricle

Magnetic resonance imaging (MRI) research has suggested that autistic individuals have hypoplasia of cerebellar lobules VI and VII, the pons, and enlargement of the fourth ventricle. Using MRI we measured the mid-sagittal area of these structures in 15 high-functioning autistic males; 15 age- and IQ-comparable male volunteers (control group I); and 15 male volunteers comparable to cases on age and parental socioeconomic status (SES) (control group II). Using ratio measures, cerebellar lobules VI-VII were found to be smaller in autistic subjects than controls in group II but not those in group I. No differences were found after multivariate analysis adjusting for mid-sagittal brain area (MSBA), age, and IQ. The size of the pons and fourth ventricle did not differ between cases and controls, although autistic subjects were noted to have a significantly larger MSBA than subjects in either control group.

Posterior vermal Purkinje cells in macaques responding during saccades, smooth pursuit, chair rotation and/or optokinetic stimulation

Anatomical locations of the Purkinje cells (P cells), showing modulations in activity during either saccadic or smooth-pursuit eye movements, during primate chair rotation, or in response to optokinetic stimulation, were studied in the posterior vermes of monkeys trained to move their eyes with a visual target. The majority (68.3%) of the responsive P cells were saccade-related units. They were located exclusively in vermal lobules VIc and VII: the oculomotor vermis. Most P cells sensitive to chair rotation were located in vermal lobules VIa,b and VIII (91.2%), designated as the paraoculomotor vermis. The P cells which modulated activity during smooth-pursuit eye movements, associated with eye position, or during optokinetic stimulation were found in both the oculomotor and paraoculomotor vermis. There were 25 P cells which modulated their activity during smooth pursuit in the oculomotor vermis. Among them, only three responded also to optokinetic stimulation but none was sensitive to chair-rotation stimulation. These findings suggest that the control of saccadic eye movements is the primary function of the oculomotor vermis.

Olivocerebellar projection to the cardiovascular zone of rabbit cerebellum

Climbing fiber responses were evoked in the medial vermal cortex of lobule VIIa by stimulation of the contralateral medial accessory olive (MAO) in anesthetized, paralyzed rabbits. Effective stimulating sites were localized in a small medial part of the caudal MAO, at 0.4–1.6 mm rostral from the caudal pole of the MAO (total length of the MAO, 4.2 mm). Stimulation of this MAO area induced depression in renal sympathetic nerve activity and this depressant response disappeared after ablation of lobule VIIa. Following injections of horseradish peroxidase into the small areas of lobule VIb, VIc, VIIa or VIIb, retrogradely labeled cells were found in corresponding small particular regions of the MAO: lobule VIb to the most caudal part, lobule VIc to the next caudal, lobule VIIa to the most rostral within the caudal MAO, and lobule VIIb further rostrally to the intermediate MAO. There was a clear disparity between the medial halves of lobules VI and VII projected from the medial MAO and the lateral halves from the lateral MAO. These results show that climbing fiber projections to lobules VI and VII are topographically organized, and that the medial region of lobule VIIa, related to cardiovascular function, receives climbing fibers from a localized small medial region of the caudal MAO.

Brainstem mossy fiber projections to lobules VIa, VIb,c, VII and VIII of the cerebellar vermis in the rat

The brainstem mossy-fiber projections to lobules VIa, VIb,c, VII and VIII of the cerebellar vermis were studied by retrograde transport of horseradish peroxidase in the rat. The distribution of labeled cells indicated that these lobules received major projections from topographically different locations of the basilar pontine nuclei and the nucleus reticularis tegmenti pontis. Lobules VIa and VIII received an additional strong projection from the lateral reticular nucleus. Moderate projections were found to reach lobule VIa from the raphe pontis and external cuneate nucleus; lobules VIb,c from the raphe pontis, lateral reticular nucleus, and a group of cells in the lateral tegmentum; lobule VII from the spinal vestibular nucleus and a lateral tegmental cell group; and lobule VIII from the medial and spinal vestibular nuclei, nucleus intercalatus and Roller of the perihypoglossal nuclei, and the main cuneate nucleus. The quantitative and topographical differences in the origin of mossy fibers suggest that these lobules may subserve slightly different functions.

Climbing fiber responses evoked in lobule VII of the posterior cerebellum from a vagal nerve in rabbits

The vagal afferent projection to the cerebellar posterior lobe was examined in decerebrate rabbits with electrophysiological techniques. Electrical stimulation of a vagal nerve at the cervical region evoked field potential responses on both sides of the posterior vermal cortex from lobule VI to VIII. The most prominent potentials appeared in the ipsilateral medial vermis of lobule VIIa. These potentials had a latency of 15.6 ms, and were negative in the molecular layer and positive in the granular layer. At a stimulation rate of 20 Hz, their amplitude was reduced by 70% of the control value at 1 Hz. Superimposed on these field potentials, unitary complex spikes were recorded at the depths of Purkinje cell layers. These results indicate that the medial vermal cortex of lobule VII receives vagal afferent signals via climbing fibers, which presumably convey cardiovascular information.

Saccadic burst neurons in the oculomotor region of the fastigial nucleus of macaque monkeys

1. The discharge of 255 neurons in the fastigial nuclei of three trained macaque monkeys was investigated during visually guided saccades. Responses of these neurons were examined also during horizontal head rotation and during microstimulation of the oculomotor vermis (lobules VIc and VII). 2. One hundred and two units were characterized by bursts of firing in response to visually guided saccades. Ninety-eight of these (96.1%) were located within the anatomic confines of the fastigial oculomotor region (FOR), on the basis of reconstruction of recording sites. During contralateral saccades, these neurons showed bursts that preceded the onset of saccades (presaccadic burst), whereas, during ipsilateral saccades, they showed bursts associated with the end of saccades (late saccadic burst). They were hence named saccadic burst neurons. Sixty-one saccadic burst neurons (62.2%) were inhibited during microstimulation of the oculomotor vermis with currents less than 10 microA. 3. All saccadic burst neurons were spontaneously active, and the resting firing rate varied considerably among units, ranging from 10 to 50 imp/s. The tonic levels of activity did not correlate significantly with eye position. 4. The presaccadic burst started 18.5 +/- 4.7 (SD) ms (n = 45) before the onset of saccades in the optimal direction (the direction associated with the maximum values of burst lead time, number of spikes per burst, and burst duration). Optimal directions covered the entire contralateral hemifield, although there was a slightly higher incidence in both horizontal and upper-oblique directions in the present sample. The duration of the presaccadic burst was highly correlated with the duration of saccade (0.85 less than or equal to r less than or equal to 0.97). 5. The late saccadic burst was most robust in the direction opposite to the optimal in each unit (the nonoptimal direction). Its onset preceded the completion of ipsilateral saccade by 30.4 +/- 5.9 ms. The lead time to the end of saccade was consistent among different units and was constant also for saccades of various sizes. Thus the late saccadic burst started even before the saccade onset when the saccade duration was less than 30 ms. Unlike the presaccadic burst, its duration was not related to the duration of saccade. 6. Discharge rates of saccadic burst neurons were correlated neither to eye positions during fixation nor to the initial eye positions before saccades. 7. Eye-position units and horizontal head-velocity units were located rostral to the FOR.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiographic characterization of [ 3H] l-glutamate binding sites in developing mouse cerebellar cortex

Postnatal changes of [ 3H] l-glutamate binding sites in mouse cerebellum were studied by in vitro autoradiography. These sites were already present at birth, their density globally increased until postnatal day 25, and at all ages it was higher when Cl − and Ca 2+ were present in the incubation buffer. At birth, these binding sites were diffused through the whole cerebellar mass, but became distinctly concentrated in the molecular and the internal granular layers by postnatal day 10. From this age on, binding site sensitivity to ions and glutamate analogues takes a different course in each layer. The external granular layer and the white matter never displayed significant amounts of binding. In the molecular layer the Cl −/Ca 2+ effect increased during ontogeny until, in adults, the ion-dependent binding was threefold higher than the ion-independent binding. Quisqualate-sensitive sites accounted for 80% of the total binding sites already at postnatal day 15, while displacement by α-amino-3-hydroxy-methyl-4-isoxazolepropionic and ibotenic acids attained the maximum (68%) at postnatal day 60.N-Methyl- d-aspartate displaced glutamate binding (50%) only in the presence of Cl − and Ca 2+. Starting from postnatal day 15, binding site density in the molecular layer of lobules VIb and VII of the vermis was lower than in other lobules. In the internal granular layer, the Cl −/Ca 2+ effect observed in young animals decreased during development. These transient binding sites were sensitive to quisqualic and ibotenic acid. In adults, the majority of glutamate binding sites were ion-independent and mainly sensitive to d,l-amino-5-phosphovaleric acid andN-methyl- d-aspartate. Throughout development and in both layers, sites displaced by kainate were present at low density and sites displaced by d,l-2-amino-4-phosphonobutyric acid were not detected. The localized postnatal changes of the [ 3H] l-glutamate binding sites were correlated with the events occurring during growth and maturation of cerebellar structures. The increase of the Cl −/Ca 2+-dependent binding in the molecular layer is simultaneous with the growth of Purkinje cell dendrites and of parallel fibres and with the formation of the synapses between them. This suggests that these binding sites are localized in these synapses. The changing pattern of sensitivity to different agonists during development might correspond to the maturation of these synapses. The low density of [ 3H] l-glutamate binding in the molecular layer of lobules VIb and VII probably indicates the presence of specific nerve projections to these areas. The decrease of ion-dependent and quisqualate-sensitive binding sites in the internal granular layer is concurrent with developmental modifications of the mossy fibre synapses with granule cell dendrites in the glomeruli. This is another example of developmentally regulated transient binding sites of this type, similar to those described in the globus pallidus and in the deep cerebellar nuclei. Despite the temporal correlation between neuronal maturation and the [ 3H] l-glutamate binding site accumulation in the developing cerebellum, it cannot be excluded that binding sites in glial cells also contributed to the described developmental patterns.

Cerebellar Control of Saccadic Eye Movements: Its Neural Mechanisms and Pathways.

Microstimulation studies on monkeys have shown that the cerebellar cortex which is related to saccadic function is located in lobules VIc and VII of the vermis. This vermal area is designated as the oculomotor vermis and characterized by low thresholds (less than 10 microA) and by saccade-related neuronal activity. The saccade evoked by the vermal stimulation has been shown to be the result of activation of Purkinje-cell axons. On the other hand, an anterograde WGA-HRP transport study has indicated that the Purkinje-cell axons of the oculomotor vermis terminate almost exclusively in a fatigial region which is designated as the fastigial oculomotor region (FOR). Microstimulation of the oculomotor vermis and the ventromedial aspect of the FOR results in saccades which differ in their horizontal directions, with vermal stimulation resulting in ipsilateral and fastigial stimulation resulting in contralateral saccades. Since the ipsilateral saccades evoked from the caudal part of the FN were suppressed by bicuculline, they were the results of stimulation of the Purkinje axons. It has been also shown that stimulation of the oculomotor vermis causes inhibition of FOR neurons. Furthermore, fastigial neurons bursting with saccades can be recorded only within the anatomical confines of the FOR. These data are consistent with the concept that signals from the vermis are transmitted to the saccadic nuclei of the brainstem via the FOR. Neurons in the FOR have been shown to project to various saccade-related nuclei, including the riMLF and PPRF. Some neurons in the FOR have divergent axon collaterals which terminate in both the vertical and horizontal preoculomotor nuclei. When the initial eye position is changed by stimulating the FN prior to visually-guided saccades, monkeys cannot compensate for the stimulation-induced movement. When the stimulation is delived 75-130 ms after the target presentation, saccades are triggered prematurely. The visuomotor processing for saccades seems to be completed during this period, which is approximately half the latency of normal saccades. When saccades were triggered prematurely at an early stage of information processing, the eyes moved first in the direction of evoked saccade and then changed the direction toward the location of the target without any intervening period. The retinal error information sampled before the stimulation was not disturbed by the cerebellar stimulation. These observations suggest that cerebellar output impulses are projected downstream to saccade-programming circuits where visual information has already been converted into motor-command signals. The cerebellum is a domain for parallel processing of visuomotor information.