Department of Pharmacology and Physiology, University of Chicago, Chicago, Illinois 60637
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ABSTRACT |
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Belton, T. and R. A. McCrea. 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.
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INTRODUCTION |
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The cerebellar cortex is subdivided into many
parasagittal modules, each of which projects to separate regions of the
cerebellar or vestibular nuclei (Hess and Voogd 1986;
Sato and Kawasaki 1991
; Voogd et al.
1996
). Efferents from the parasagittal zones that span the
cerebellar flocculus and ventral paraflocculus project to brain stem
pathways that are involved in controlling the vestibulo-ocular reflex
(VOR) (Ito et al. 1977
; Lisberger et al.
1994a
; Zhang et al. 1995
), which produces
rotations of the eyes when the head moves so that gaze is stabilized in
space. It is well established that this region of the cerebellum is
essential for using visual feedback to change the gain of the VOR when
a change in gaze velocity is required to maintain image stability on
the retina (Ito 1972
; Lisberger et al.
1994b
; Miles et al. 1980
; Robinson
1976
). In primates the floccular region is essential for
producing smooth pursuit eye movements and for changing the gain of the
VOR when it fails to stabilize images on the retina during passive
whole body rotation (Takemori and Cohen 1974
; Zee
et al. 1981
). In head-restrained monkeys, many of the Purkinje
(Pk) cells in the flocculus and ventral paraflocculus code eye velocity
during smooth pursuit eye movements and head velocity during
suppression of the VOR (Lisberger and Fuchs 1978
;
Miles et al. 1980
). The latter observation suggests the
possibility that the floccular region helps to coordinate eye and head
movements during active gaze shifts by modifying the VOR.
We recorded the firing behavior of Pk cells in the floccular region of squirrel monkeys during active head movements produced during smooth pursuit tracking and saccadic gaze shifts. The effect of inactivating the flocculus and ventral paraflocculus by muscimol injection on smooth pursuit tracking was also studied. The results suggest that the signals produced by Pk cells in the floccular region are neither necessary nor sufficient for coordinating gaze when active head movements contribute to saccades or smooth tracking.
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METHODS |
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Squirrel monkeys were seated on a vestibular turntable. The head was attached to a rod that rotated within a ball bearing assembly that was fixed to the turntable. The apparatus allowed the monkey to generate angular head movements (±45°) in the plane of the horizontal semicircular canal. A clamp above the bearing assembly permitted quick transition from a head-fixed to a head-free state. Eye and head movements were measured with a magnetic search coil system (Neurodata). Animals were trained to fixate and pursue a visual target (<0.25° diam) projected onto the surrounding screen from the turntable with mirror galvanometers. Signals related to head, eye, turntable, and target position were sampled at 200-500 Hz and saved on a computer for off-line analysis.
Single-unit recordings from Pk cells in the flocculus and ventral paraflocculus were obtained with tungsten microelectrodes that were advanced into the floccular region with an hydraulic microdrive attached to the monkey's head. The responses of Pk cells were recorded during 0.5-Hz (40°/s peak velocity) sinusoidal smooth ocular pursuit in the head-fixed condition and during combined eye-head pursuit in the head-free condition. The monkeys were rewarded for accurately following the target with their eyes, regardless of the contribution of the head movement to pursuit. However, they typically followed the target primarily with head movements in the head-free condition. The contribution of head movements to gaze velocity during head-free pursuit varied from moment to moment, but on average 74% of gaze velocity was produced by smooth active head movements. Unit responses were also recorded during whole body rotation while the monkey fixated earth stationary targets and head stationary targets (VOR cancellation) and during spontaneous saccadic gaze shifts in the absence of a target. Unit responses to sinusoidal stimuli were quantified by fitting sinusoidal functions to averaged records of 20-80 cycles in which epochs related to saccades had been excluded. Unit sensitivity to passive head velocity was estimated in the VOR cancellation paradigm. The sensitivity of Pk cells to active head movements during combined eye-head pursuit was estimated by subtraction of a signal related to the eye velocity component of pursuit. Unit responses during saccades were assessed from averages of 12 gaze saccades whose direction and amplitude were similar.
The floccular region was unilaterally inactivated in two monkeys by
pressure injection of 1.2-1.3 µl of a 2% muscimol solution over a
10-min period (Partsalis et al. 1995; Thach et
al. 1992
). In each monkey the injection was centered in a
region that contained the highest concentration of Pk cells whose
firing behavior was related to horizontal smooth pursuit eye movements
and to head velocity during VOR cancellation. In one monkey the
location of the injection site was verified histologically. The gain of
the VOR was periodically checked after the injection to insure that vestibular neurons related to VOR pathways were not directly affected by the injection.
The variability in unit responses and eye movements cited in the text and illustrated in figures is expressed as SE.
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RESULTS |
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Single-unit recordings during smooth pursuit eye and head movements
A total of 187 floccular region Pk cells were studied in three
monkeys whose simple spike activity was related to horizontal smooth
pursuit eye movements or whole-body rotation when the visual target
moved with the head. The majority of these cells (128/187) were studied
during combined eye-head pursuit in the head-free condition. One-half
of the Pk cells encountered (89/179, 50%) were only sensitive to eye
velocity (Ev Pk cells) during pursuit and were not sensitive to head
velocity. The other one-half (90/179) were sensitive to head velocity
during cancellation of the VOR and to Ev during smooth pursuit. These
cells will be referred to as Gv Pk cells because of the qualitative
similarity of their responses during VOR cancellation to Gv Pk cells in
the floccular region of the macaque (Lisberger and Fuchs
1978). The firing rate of Gv Pk cells was modulated in phase
with gaze velocity in both the head-fixed and head-free conditions,
although their sensitivity to gaze velocity was usually reduced during
head free pursuit and VOR cancellation.
Figure 1 shows averaged responses of a typical Ev Pk cell and a Gv Pk cell during 36-65 cycles of 0.5 Hz sinusoidal ocular pursuit in the head-fixed condition (A1), combined eye and head pursuit in the head-free condition (A2), and during VOR cancellation in the head-fixed condition (A3). The top dashed traces in each column are the average velocity of the target (Tv in A1 and A2) or turntable (A3). The gaze velocity evoked in each paradigm was similar. In the head-fixed condition, the modulation in gaze velocity was produced by eye velocity during ocular pursuit. However, the modulation in gaze velocity was produced primarily by head velocity when active head movements were generated to pursue the target or when the when the head and target were passively rotated in tandem in the VOR cancellation paradigm. The histograms are the average responses of typical Ev (top row) and Gv (bottom row) Pk cells in each paradigm.
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The firing rate of Ev Pk cells was strongly modulated during smooth pursuit eye movements and was linearly related to eye velocity during eye-head pursuit and VOR cancellation. Although most of these cells were not sensitive to eye position during steady fixation, their responses significantly lagged eye velocity (mean phase lag during ocular pursuit = 52°±3.8°). In a few cells (21%), the lag was attributable to an eye position signal, but most Ev Pk cells were not sensitive to eye position during steady fixation.
Gv Pk cells tended to fire in phase with gaze velocity during ocular pursuit, head-free pursuit, and VOR cancellation. They were less sensitive to head velocity (mean gain = 0.59 ± 0.05 sp/s/°/s; n = 73) than to eye velocity (mean gain = 1.23 ± 0.08 sp/s/°/s), although their head velocity sensitivity during VOR cancellation and head-free pursuit was similar (dark striped bars in Fig. 1B). The relatively low sensitivity to head velocity made Gv Pk cells less sensitive to head-free pursuit than ocular pursuit. Because Ev Pk cells were not sensitive to head velocity, the average modulation of the entire population of Pk cells was reduced by more than one-half during combined eye-head pursuit compared with ocular pursuit (shaded bars in Fig. 1B).
Flocculus and ventral paraflocculus Pk cells were not sensitive to gaze
or head velocity during gaze saccades. Figure 1C shows the
averaged response of a Gv Pk cell during 12 ipsilateral (on-direction) and twelve contralateral combined eye-head saccades that were spontaneously generated in the absence of a visual target. The eye
velocity sensitivity of this Gv Pk cell during ocular pursuit was 2.16 spikes/s °1 s
1. Its sensitivity to head
velocity during VOR cancellation was 0.80 sp/s °
1
s
1. If the unit had been similarly sensitive to eye and
head velocity during gaze saccades its peak firing rate would have been
>600 sp/s (dotted trace superimposed on firing rate histograms in Fig. 1C). This Gv Pk cell's sensitivity to head velocity alone
would have produced a change in firing rate exceeding 100 sp/s (shaded dashed trace in Fig. 1, C1 and
C2). However, this unit, like every other Pk
cell encountered in the floccular region, was sensitive neither to Gv
nor to Hv during gaze saccades.
In sum, the firing rate of Pk cells in the floccular region of the squirrel monkey was strongly related to smooth pursuit eye movements. These cells were not sensitive to gaze velocity during saccades, and as a population they were only 54% as sensitive to gaze velocity during combined eye-head pursuit as during ocular pursuit.
Effects of inactivating the floccular region on eye and head pursuit
The effects of a unilateral injection of 1.2 µl of 2% muscimol into the floccular region on ocular pursuit, head-free pursuit, and VOR cancellation in one squirrel monkey are shown in Fig. 2. Similar results were observed in a second animal. The injection produced a weak (2-6°/s) spontaneous nystagmus in the dark (not shown) but had no effect on the gain of the VOR, which suggests that the muscimol did not directly affect processing in brain stem VOR pathways. Sample behavioral responses evoked immediately before the injection are shown in Fig. 2, A1-A3. Sample responses evoked after muscimol injection are shown in Fig. 2, B1-B3. Averaged desaccaded records of Gv evoked during pursuit and VOR cancellation are shown in Fig. 2, C1-C3. The effect of muscimol on the eye velocity evoked during ocular pursuit is shown in Fig. 2D1. The effect of the muscimol injection on the ability of the monkey to suppress its VOR during active head pursuit movements and passive whole body rotation is shown in Fig. 2, D2 and D3.
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Unilateral inactivation of the floccular region disrupted the monkey's
ability to generate ocular pursuit (Fig. 2, C1
and D1) but had little effect on its ability to
pursue targets in the head-free condition
(A2-C2). Peak gaze
velocity was reduced by ~50% during both ocular pursuit and VOR
cancellation. The effect on ocular pursuit was bilateral, although
asymmetric (Fig. 2D1), as has been previously
observed (Waespe et al. 1983).
Because the VOR is a reflex that functions to stabilize gaze in space, it must be canceled during head free pursuit. The effect of muscimol injection on the monkey's ability to cancel its VOR during passive whole body rotation and during combined eye-head pursuit is shown in Fig. 2, D2 and D3. After muscimol injection the monkey was able to suppress eye movements during combined eye-head pursuit (Fig. 2D2) but not during passive whole-body rotation in the head-fixed condition (Fig. 2D3). Thus the floccular region was apparently necessary for cancellation of the VOR evoked by passive whole-body rotation but not for canceling the VOR during head movements that were actively produced.
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DISCUSSION |
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To keep a moving visual image on the fovea, the eye must be moved at the speed of the image. In the absence of head or body movements this can be accomplished by generating smooth pursuit eye movements. However, the eye has a limited range of motion that can be quickly exceeded when target velocity is high or when the moving image is near the eyes. The ocular pursuit movement then has to be supplemented with active movements of the head and/or body. The floccular region of the cerebellar cortex is an important part of the neural substrate that is involved in producing smooth pursuit eye movements, but it appears to have little to do with producing active head movements or with coordinating eye and head movements during active gaze shifts. The Pk cells in that region are not sensitive to saccadic gaze shifts and are much less sensitive to active head movements during combined eye-head smooth tracking than to eye movements during ocular pursuit. Inactivation of the floccular region compromises ocular pursuit but has little effect on the ability of monkeys to pursue visual targets with smooth head movements. These observations imply that the floccular region is essential for generating smooth pursuit eye movements but not for controlling gaze.
We referred to Gv Pk cells as Gv Pk cells in this study only because
cells with similar characteristics in the macaque monkey have been
labeled this way. In those animals Gv Pk cells have nearly equal
sensitivity to eye velocity during smooth pursuit eye movements and to
head velocity during VOR cancellation (Lisberger and Fuchs
1978; Miles et al. 1980
). It seems more likely
that the similarity of responses during VOR cancellation and smooth pursuit reflect the propensity of rhesus monkeys to place a heavy reliance on circuitry related to visual feedback to cancel their VOR
than that the floccular region is related to controlling gaze per se.
Squirrel monkeys have a more limited oculomotor range and are
presumably less inclined to rely entirely on ocular pursuit to track
moving targets. In fact, these monkeys like most vertebrates prefer to
track moving targets with head movements when given the opportunity,
and it is likely that this strategy utilizes other mechanisms for
canceling the VOR.
When head or trunk movements contribute to gaze velocity, the VOR must
be cancelled to prevent counter-rotation of the eyes. The signal used
to cancel the VOR could be an internal estimate of head velocity
derived from visual and/or vestibular sensory reafferent signals or an
efference copy of active head movement commands (Robinson
1982). Our results suggest that the mechanisms for suppressing
the VOR during active and passive head movements are quite different
and that the flocculus and ventral paraflocculus are needed only when
the movement is not self-generated. The visual and vestibular estimates
of passive head movement available in the flocculus are apparently
necessary for canceling the reflexive eye movements produced by passive
perturbations of the head or body. However during active head movements
signals related to the active head movements themselves are available
to cancel signals in VOR pathways (McCrea et al. 1996
),
and there may be no need to use a central estimate of head velocity to
cancel the VOR.
In conclusion, the combination of visual, vestibular, and eye movement signals generated by cells in the floccular region of the cerebellum helps the VOR to produce smooth eye movements that prevent image slip on the retina. This smooth eye movement control is essential for preventing image slip caused by passive perturbations of the head in space, but it is neither necessary nor sufficient for coordinating eye and head movements when both motor systems are used to prevent image slip. The implication is that each functional module in the cerebellar cortex, like the horizontal eye movement zone of the flocculus, functions to improve the performance of individual movement programs, like the horizontal VOR, rather than coordinate the performance of several synergistic motor systems.
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ACKNOWLEDGMENTS |
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This work was supported by National Institute of Health Grants RO1-EY-08041 and P60-DC-02072.
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FOOTNOTES |
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Address for reprint requests: R. A. McCrea, Abbott 07, Dept. of Pharmacology and Physiology, 5830 S. Ellis Ave., Chicago, IL 60637.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 21 January 1999; accepted in final form 25 February 1999.
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REFERENCES |
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