Motor dynamics encoding in cat cerebellar flocculus middle zone during optokinetic eye movements

We investigated the relationship between eye movement and simple-spike (SS) frequency of Purkinje cells in the cerebellar flocculus middle zone during the optokinetic response (OKR) in alert cats. The OKR was elicited by a sequence of a constant-speed visual pattern movement in one direction for 1 s and then in the opposite direction for 1 s. Quick-phase-free trials were selected. Sixty-six cells had direction-selective complex spike (CS) activity that was modulated during horizontal (preferring contraversive) but not vertical stimuli. The SS activity was modulated during horizontal OKR, preferring ipsiversive stimuli. Forty-one cells had well-modulated activity and were suitable for the regression model. In these cells, an inverse dynamics approach was applied, and the time course of the SS rate was reconstructed, with mean coefficient of determination 0.76, by a linear weighted superposition of the eye acceleration (mean coefficient, 0.056 spikes/s per deg/s(2)), velocity (5.10 spikes/s per deg/s), position (-2.40 spikes/s per deg), and constant (mean 34.3 spikes/s) terms, using a time delay (mean 11 ms) from the unit response to the eye response. The velocity and acceleration terms contributed to the increase in the reconstructed SS rates during ipsilateral movements, whereas the position term contributed during contralateral movements. The standard regression coefficient analyses revealed that the contribution of the velocity term (mean coefficient 0.81) was predominant over the acceleration (0.03) and position (-0.17) terms. Forward selection analysis revealed three cell types: Velocity-Position-Acceleration type (n = 27): velocity, position, and acceleration terms are significant (P < 0.05); Velocity-Position type (n = 12): velocity and position terms are significant; and Velocity-Acceleration type (n = 2): velocity and acceleration terms are significant. Using the set of coefficients obtained by regression of the response to a 5 deg/s stimulus velocity, the SS rates during higher (10, 20, and 40 deg/s) stimulus velocities were successfully reconstructed, suggesting generality of the model. The eye-position information encoded in the SS firing during the OKR was relative but not absolute in the sense that the magnitude of the position shift from the initial eye position (0 deg/s velocity) contributed to firing rate changes, but the initial eye position did not. It is concluded that 1) the SS firing frequency in the cat middle zone encodes the velocity and acceleration information for counteracting the viscosity and inertia forces respectively, during short-duration horizontal OKR and 2) the apparent position information encoded in the SS firing is not appropriate for counteracting the elastic force during the OKR.     

Motor dynamics encoding in the rostral zone of the cat cerebellar flocculus during vertical optokinetic eye movements

The complex spike (CS) and simple spike (SS) activities of Purkinje cells in the rostral zone of the cerebellar flocculus were recorded in alert cats during optokinetic responses (OKR) elicited by a stimulus sequence consisting of a constant-speed visual pattern movement in one direction for 1 s and then in the opposite direction for 1 s. The quick-phase-free trials were selected. Ninety-eight cells were identified as rostral zone cells by the direction-selective CS activity that was modulated during vertical but not horizontal stimuli. In most of the majority population (88 cells), with an increasing CS firing rate during upward OKR and an increasing SS rate during downward OKR, the inverse dynamics approach was successful and the time course of the SS rate was reconstructed (mean coefficient of determination, 0.70 and 0.72 during upward and downward stimuli, respectively) by a linear weighted superposition of the eye acceleration, velocity, position, and constant terms, at a given time delay (mean 10 ms) from the unit response to the eye-movement response. Standard regression coefficient (SRC) analysis revealed that the contribution of the velocity term (mean SRC 0.98 for upward and 0.80 for downward) to regression was dominant over acceleration (mean SRC 0.018 and 0.058) and position (-0.14 and -0.12) terms. The velocity coefficient during upward stimuli (6.6 spikes/s per degree/s) was significantly (P<0.01) larger than that during downward stimuli (4.9 spikes/s per degree/s). In most of the minority population (10 cells), with both CS and SS firing rates increasing during upward OKR, the inverse dynamics approach was not successful. It is concluded that 1) in the cat rostral zone Purkinje cells, in which the preferred direction is upward for CS and downward for SS, eye velocity and acceleration information is encoded in SS firing to counteract the viscosity and inertia forces, respectively, on the eye during vertical OKR; 2) the eye position information encoded in SS firing is inappropriate for counteracting the elastic force; 3) encoding of eye velocity information during upward OKR is quantitatively different from that during downward OKR: SS firing modulation is larger for upward than for downward OKR of the same amplitude; and 4) encoding of motor dynamics is obscure in cells in which the preferred direction is upward for both CS and SS.     

Role of cerebellar flocculus in adaptive interaction between optokinetic eye movement response and vestibulo-ocular reflex in pigmented rabbits

Summary Sustained sinusoidal oscillation of a striped cylindrical screen around a stationary, alert pigmented rabbit with certain parameters (for 4h, 5°, 7.5°, or 10° peak-to-peak, 0.1 or 0.2 Hz) adaptively modified not only the horizontal optokinetic response (HOKR) but also the horizontal vestibulo-ocular reflex (HVOR). The major effects thus obtained during 4 h were an increase in the HOKR gain by 0.23, and that of the HVOR gain by 0.18. Bilateral destruction of floccular Purkinje cells with microinjection of kainic acid abolished these effects on both HOKR and HVOR. Single unit activities of floccular Purkinje cells were recorded from the floccular areas related to horizontal eye movements (H-zone) with local stimulus effects. Most H-zone Purkinje cells normally exhibited modulation of simple spike discharge in phase with screen velocity and out of phase with turntable velocity. Sustained screen oscillation (7.5°, 0.1 Hz) for 1 h increased the simple spike responses not only to screen but also to turntable oscillation. No such changes were observed in other floccular areas. These observations suggest that sustained optokinetic stimulations induce adaptation of HVOR through an interaction of retinal slip and head velocity signals within the flocculus or its related neuronal tissues.     

Purkinje cell activity in the middle zone of the cerebellar flocculus during optokinetic and vestibular eye movement in cats

Based on the inverse dynamics theory, a previous paper reconstructed simple-spike (SS) firing rates of Purkinje cells in the cat's flocculus middle-zone by a linear-weighted summation of eye acceleration, velocity, and position during optokinetic response (OKR). The present study investigated the SS rates during combined optokinetic and vestibular stimuli of the cells recorded in the previous paper. During the sinusoidal vestibuloocular reflex (VOR) in the light (VORL) and in the dark (VORD) the firing modulation was small. During VOR suppression (VORS) by head and visual-pattern rotation in the same direction, the modulation was deep, with the peak coinciding roughly with peak ipsiversive head velocity. During VOR enhancement (VORE), the modulation was deep, with the peak coinciding roughly with peak contraversive head velocity. If we interpret these data in relation to eye and head movements, the cells in the cat were comparable to the horizontal-gaze-velocity Purkinje cells in the monkey that encode a linear summation of eye and head velocity signals. Alternatively, if we interpret the data on the basis of the inverse dynamics theory, the SS rates during VORL, VORS, and VORE were well-fitted by the OKR components of the movements (subtraction of VORD from VORL, VORS, and VORE eye movements, respectively), but not by the whole movements, using the coefficients calculated during OKR. It is concluded that the data are interpretable by both theories when the VOR gain (eye movement/head movement) is close to 1 and the firing is dominated by eye velocity information.     

Rehearsal by eye movement improves visuomotor performance in cerebellar patients

In order to assess the effect of rehearsal by eye movement alone on visuomotor performance, the eye movements and visually guided stepping of two cerebellar patients were monitored before and after a first and second batch of eye-movement rehearsals, in which patients made saccadic eye movements to the first 6 footfall targets (in a sequence of 18) whilst standing stationary at the start of the walkway. There was a marked improvement in oculomotor and locomotor performance following the second batch of eye-movement rehearsal. Both patients showed reduced occurrence of saccadic dysmetria, evident as a significant increase in the proportion of single to multi-saccadic eye movements (from 46 to 77% for DB and from 75 to 94% for TP). This was accompanied by increased regularity and accuracy of stepping in both patients, and decreased stance and double support phase durations (one patient only). Separate testing confirmed that these improvements in eye movements and stepping did not result from simple repetition of the task. This is the first demonstration of a technique--rehearsal by eye movement--that improves the visuomotor performance of cerebellar patients. It is compelling evidence for our proposal that during visually guided stepping the locomotor control system is dependent on assistance from the oculomotor control system.     

Contribution of eye muscle proprioception to velocity-response characteristics of eye movements: involvement of the cerebellar flocculus.

The vestibulo-ocular reflex (VOR) and optokinetic nystagmus (OKN) were examined in alert pigmented rabbits following interruption of proprioceptive afferents from the extraocular muscles in one eye by surgical section of the ophthalmic branch of the trigeminal nerve (V1 nerve). Deficits were mainly produced in movement dynamics of the ipsilateral eye including reduction of (1) the VOR gain at a high frequency of head rotation, (2) the OKN gain and (3) the velocity of quick eye movements in the OKN. In some of the rabbits examined, the cerebellar flocculus was lesioned by local injection of kainic acid before severance of the V1 nerve. No significant additional reductions of VOR or OKN gains were produced by V1 nerve section in the flocculus-lesioned rabbits. These results suggest that proprioceptive signals from eye muscles act to improve VOR and OKN dynamics through the neuronal mechanisms involving the cerebellar flocculus.     

Role of primate cerebellar lobulus petrosus of paraflocculus in smooth pursuit eye movement control revealed by chemical lesion

The primate lobulus petrosus (LP) of the cerebellar paraflocculus receives inputs from visual system-related pontine nuclei, and projects to eye movement-related cerebellar nuclei. To reveal a potential involvement of LP in oculomotor control, we lesioned LP unilaterally by local injections of ibotenic acid in three Macaca fuscata. We examined the effects of lesion on eye movements evoked by step (3 degrees )-ramp (5-15 degrees/s) moving target. To step-ramp moving target, the monkeys showed an initial slow eye movement and later a small catch-up saccade, which was followed by the post-saccadic pursuit nearly matching to the velocity of the ramp target motion. After LP lesioning, the velocity of post-saccadic pursuits in the ipsiversive and down-ward directions decreased by 20-40% in all three monkeys. These deficits lasted for at least 1 month, and some recovery was observed. In the amplitudes of catch-up saccades, no consistent changes were seen among the three monkeys after LP lesioning. These results suggest an involvement of LP in the primate smooth pursuit eye movement control.     

Non-motoneurons in the facial and motor trigeminal nuclei projecting to the cerebellar flocculus in the cat

Summary The cerebellar projection from the facial and motor trigeminal nuclei was studied in the cat by means of retrograde axonal transport of wheat germ agglutinin-horseradish peroxidase and fluorescent tracers. The feline facial nucleus was cytoarchitectonically subdivided into ventromedial, ventrolateral, lateral, dorsal, intermediate and medial divisions (see Papez 1927), and the motor trigeminal nucleus into medial, ventral, intermediate, lateral and dorsal divisions. The neurons in the facial and motor trigeminal nuclei were classified as small (ovoid to round cells with a maximum diameter of the cell body of about 20 m) or large (polygonal to round cells with maximum diameter of about 40 m). After floccular injections of the wheat germ agglutininhorseradish peroxidase complex, retrogradely labelled cells were found throughout the facial nucleus, but especially in its medial and dorsal divisions. In the motor trigeminal nucleus, labelled neurons were found only in the ventral, intermediate and lateral divisions. Cases with tracer deposition (implants or injections) in other parts of the cerebellar cortex or nuclei were all negative. All facial and motor trigeminal neurons labelled after floccular injections were smaller than the neurons labelled after injections in the facial mimic and masticatory muscles, and only single-labelled neurons were found following floccular injections of Fluoro-Gold and muscular injections of rhodamine-B-isothiocyanate in the same animals. These observations strongly suggest that the neurons in the facial and motor trigeminal nuclei which project to flocculus are of the non-motoneuron type.     

Functional localization in the rabbit's cerebellar flocculus determined in relationship with eye movements

In alert albino rabbits, the cerebellar flocculus was mapped for the effect of its local stimulation upon eye movements. Stimulation through a glass pipette electrode placed in a relatively rostral area induced abduction of the ipsilateral eye. That in a relatively caudal area resulted in a downward movement of the ipsilateral eye, accompanied by an upward movement of the contralateral eye. Intorsion of the contralateral eye was also evoked from a relatively dorsal area. These results indicate that Purkinje cells connected with different components of the vestibulo-ocular reflex arc have a differential localization within the flocculus.     

Role of the cerebellar flocculus region in the coordination of eye and head movements during gaze pursuit

The contribution of the flocculus region of the cerebellum to horizontal gaze pursuit was studied in squirrel monkeys. When the head was free to move, the monkeys pursued targets with a combination of smooth eye and head movements; with the majority of the gaze velocity produced by smooth tracking head movements. In the accompanying study we reported that the flocculus region was necessary for cancellation of the vestibuloocular reflex (VOR) evoked by passive whole body rotation. The question addressed in this study was whether the flocculus region of the cerebellum also plays a role in canceling the VOR produced by active head movements during gaze pursuit. The firing behavior of 121 Purkinje (Pk) cells that were sensitive to horizontal smooth pursuit eye movements was studied. The sample included 66 eye velocity Pk cells and 55 gaze velocity Pk cells. All of the cells remained sensitive to smooth pursuit eye movements during combined eye and head tracking. Eye velocity Pk cells were insensitive to smooth pursuit head movements. Gaze velocity Pk cells were nearly as sensitive to active smooth pursuit head movements as they were passive whole body rotation; but they were less than half as sensitive ( approximately 43%) to smooth pursuit head movements as they were to smooth pursuit eye movements. Considered as a whole, the Pk cells in the flocculus region of the cerebellar cortex were <20% as sensitive to smooth pursuit head movements as they were to smooth pursuit eye movements, which suggests that this region does not produce signals sufficient to cancel the VOR during smooth head tracking. The comparative effect of injections of muscimol into the flocculus region on smooth pursuit eye and head movements was studied in two monkeys. Muscimol inactivation of the flocculus region profoundly affected smooth pursuit eye movements but had little effect on smooth pursuit head movements or on smooth tracking of visual targets when the head was free to move. We conclude that the signals produced by flocculus region Pk cells are neither necessary nor sufficient to cancel the VOR during gaze pursuit.     

Contribution of the cerebellar flocculus to gaze control during active head movements.

The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye-head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body.     

Monocular eye movement in the cat: its corticotectal pathway

The corticotectal pathway from the fundus of the cat's coronal sulcus (CORo) from which monocular movements of contralateral eye were evoked was studied using electrophysiological and anatomical techniques. Neurons in the CORo were activated antidromically by electrical stimulation of the deep layer of the superior colliculus (SC). Labeled cells were found in the CORo following horseradish peroxidase injection in the SC.     

Specific patterns of neuronal connexions involved in the control of the rabbit's vestibulo-ocular reflexes by the cerebellar flocculus.

1. In anaesthetized albino rabbits, the occurrence of Purkinje cell inhibition on canal-ocular reflexes was surveyed with a reflex testing method. 2. Test reflexes were elicited by electrical stimulation of the semicircular canals. The results were appaised by recording potentials and tension from extraocular muscles. Twelve reflexes were defined in terms of the receptor canal and the effector muscle. 3. Conditioning electrical stimuli were applied to the flocculus, the inferior olive, and optic pathways at the retinae, optic chiasm, pretectal area and upper medulla. 4. The conditioning stimulation at the ipsilateral flocculus induced depression in six of the twelve canal-ocular reflexes; four of the six arose from the anterior canal and the remaining two from the horizontal canal. 5. The effect of stimulation of the contralateral inferior olive was similar to that of the ipsilateral flocculus, though less clear in two of the four reflexes from the anterior canal because of a contaminating effect. 6. The two reflexes from the horizontal canal were depressed by stimulation of the ipsilateral optic pathway which reached the ipsilateral flocculus via the contralateral pretectal area and inferior olive. 7. The four reflexes from the anterior canal were affected by stimulation of optic pathways in a different manner from each other. One was depressed from the contralateral retina via the ipsilateral pretectal area, while another was depressed from the ipsilateral retina via the contralateral pretectal area, though only occasionally. The third reflex was depressed from the ipsilateral pretectal area but not from the retina. The fourth was affected from neither the retina nor the pretectal area. 8. On the basis of latency measurements, it was concluded that the depression of canal-ocular reflexes was due to inhibition of relay neurones of the testing reflexes by flocculus Purkinje cells which were activated either directly, or indirectly through olivocerebellar climbing fibre afferents. 9. The above conclusion was supported by the observation that the depression induced by stimulation of the inferior olive and optic pathways was abolished by acute destruction of the ipsilateral flocculus. 10. The possible functional significance of the specific patterns of connexions from flocculus Purkinje cells to canal-ocular reflex pathways is discussed, and specialization among flocculus Purkinje cells in relationship with vestibulo-ocular reflexes is postulated.     

Responses of cerebellar units to a passive movement in the decerebrate cat

Summary The responses of mossy fibers (MF), granular cells (GrC) and Purkinje cells (PC) were recorded in the cerebellum of the decerebrate cat during a passive movement about the forepaw wrist joint. Three main discharge patterns containing information about all the static and dynamic parameters of the movement were found. Simultaneous recording of complex spikes (CS) and simple spikes (SS) showed that the activity of PC can be modulated through either MF or CF input channels alone or both together. In the latter case SS and CS discharge most commonly showed an opposite behavior, in which the increase of the frequency of one type of spike was accompanied by a decrease of the frequency of the other type. Both inputs displayed tonic and phasic characteristics and all the qualitative discharge patterns observed. Therefore it was concluded that aside from differences in the discharge frequency, both inputs are able to directly signal peripheral events.     

Topographical representation of vestibulo-ocular reflexes in rabbit cerebellar flocculus

In anaesthetized albino rabbits, the cerebellar flocculus was systematically mapped with a glass microelectrode to identify the location of Purkinje cells that inhibit specific vestibulo-ocular reflex pathways. The effects of microstimulation of the flocculus Purkinje cell layer on vestibular nerve-evoked reflexes to ipsilateral medial rectus, ipsilateral superior rectus and contralateral inferior oblique muscles were explored by recording electromyographically. Visual climbing fibre inputs to the flocculus were also studied by mapping field potentials evoked from both retinae.The results suggest that there are microzones in the flocculus that are related specifically to these three vestibulo-ocular reflex pathways and to different visual climbing fibre pathways.     

Effect of passive eye movement on retinogeniculate transmission in the cat

1. The nature and time window of interaction between passive phasic eye movement signals and visual stimuli were studied for dorsal lateral geniculate nucleus (LGNd) neurons in the cat. Extracellular recordings were made from single neurons in layer A of the left LGNd of anesthetized paralyzed cats in response to a normalized visual stimulus presented to the right eye at each of several times of movement of the left eye. The left eye was moved passively at a fixed amplitude and velocity while varying the movement onset time with respect to the visual stimulus onset in a randomized and interleaved fashion. Visual stimuli consisted of square-wave modulated circular spots of appropriate contrast, sign, and size to elicit an optimal excitatory response when placed in the neurons' receptive-field (RF) center. 2. Interactions were analyzed for 78 neurons (33 X-neurons, 43 Y-neurons, and 2 physiologically unclassified neurons) on 25-65 trials of identical visual stimuli for each of eight times of eye movement. 3. Sixty percent (47/78) of the neurons tested had a significant eye movement effect (ANOVA, P less than 0.05) on some aspect of their visual response. Of these 47 neurons, 42 (89%) had a significant (P less than 0.05) effect of an appropriately timed eye movement on the number of action potentials, 36 (77%) had a significant effect on the mean peak firing rate, and 31 (66%) were significantly affected as evaluated by both criteria. 4. The eye movement effect on the neurons' visual responses was primarily facilitatory. Facilitation was observed for 37 (79%) of the affected neurons. For 25 of these 37 neurons (68%), the facilitation was significant (P less than 0.05) as evaluated by both criteria (number of action potentials and mean peak firing rate). Ten (21%) of the affected neurons had their visual response significantly inhibited (P less than 0.05). 5. Sixty percent (46/78) of the neurons were tested for the effect of eye movement on both visually elicited activity (visual stimulus contrast = 2 times threshold) and spontaneous activity (contrast = 0). Eye movement significantly affected the visual response of 23 (50%) of these neurons. However, spontaneous activity was significantly affected for only nine (20%) of these neurons. The interaction of the eye movement and visual signals was nonlinear. 6. Nine of 12 neurons (75%) tested had a directionally selective effect of eye movement on the visual response, with most (8/9) preferring the temporal ward direction.(ABSTRACT TRUNCATED AT 400 WORDS)