SummaryExecution of accurate eye movements depends critically on the cerebellum1,2,3, suggesting that Purkinje cells (P-cells) may predict motion of the eye. Yet, this encoding has remained a long-standing puzzle: P-cells show little consistent modulation with respect to saccade amplitude4,5 or direction4, and critically, their discharge lasts longer than duration of a saccade6,7. Here, we analyzed P-cell discharge in the oculomotor vermis of behaving monkeys8,9 and found neurons that increased or decreased their activity during saccades. We estimated the combined effect of these two populations via their projections on the caudal fastigial nucleus (cFN) and uncovered a simple-spike population response that precisely predicted the real-time motion of the eye. When we organized the P-cells according to each cell's complex-spike directional tuning, the simple-spike population response predicted both the real-time speed and direction of saccade multiplicatively via a gain-field. This suggests that the cerebellum predicts the real-time motion of the eye during saccades via the combined inputs of P-cells onto individual nucleus neurons. A gain-field encoding of simple spikes emerges if the P-cells that project onto a nucleus neuron are not selected at random, but share a common complex-spike property.

Summary The primary output cells of the cerebellar cortex, Purkinje cells (P-cells), make kinematic predictions about ongoing movements via high-frequency simple spikes (SS), but receive sensory error information about that movement via low-frequency complex spikes (CS). How is the vector space of sensory errors encoded by this low-frequency signal? Here, we measured P-cell activity in the oculomotor vermis during saccades, then followed the chain of events from experience of visual error, generation of CS, modulation of SS, and ultimately change in motor-output. We found that while error direction affected probability of CS, error magnitude altered its temporal distribution. Production of CS changed the SS on the next trial, but regardless of the actual visual error, this change biased the movement only along a vector that was parallel to the P-cell’s preferred error. From these results, we inferred the anatomy of a sensory-to-motor adaptive controller that transformed visual error vectors into motor-corrections.

Soetedjo R, Kojima Y, Fuchs AF. Complex spike activity in the oculomotor vermis of the cerebellum: a vectorial error signal for saccade motor learning ? J Neurophysiol 100: 1949-1966, 2008. First published July 23, 2008 doi:10.1152/jn.90526.2008. Brain stem signals that generate saccadic eye movements originate in the superior colliculus. They reach the pontine burst generator for horizontal saccades via short-latency pathways and a longer pathway through the oculomotor vermis (OMV) of the cerebellum. Lesion studies implicate the OMV in the adaptation of saccade amplitude that occurs when saccades become inaccurate because of extraocular muscle weakness or behavioral manipulations. We studied the nature of the possible error signal that might drive adaptation by examining the complex spike (CS) activity of vermis Purkinje (P-) cells in monkeys. We produced a saccade error by displacing the target as a saccade was made toward it; a corrective saccade ϳ200 ms later eliminated the resulting error. In most P-cells, the probability of CS firing changed, but only in the error interval between the primary and corrective saccade. For most P-cells, CSs occurred in a tight cluster ϳ100 ms after error onset. The probability of CS occurrence depended on both error direction and size. Across our sample, all error directions were represented; most had a horizontal component. In more than one half of our P-cells, the probability of CS occurrence was greatest for error sizes Ͻ5°a nd less for larger errors. In the remaining cells, there was a uniform increased probability of CS occurrence for all errors Յ7-9°. CS responses disappeared when the target was extinguished during a saccade. We discuss the properties of this putative CS error signal in the context of the characteristics of saccade adaptation produced by the target displacement paradigm.

Throughout life, the oculomotor system can correct itself when saccadic eye movements become inaccurate. This adaptation mechanism can be engaged in the laboratory by displacing the target when the saccade toward it is in flight. Forward and backward target displacements cause gradual increases and decreases in saccade amplitude, respectively. Equipped with this paradigm, we asked whether Purkinje cells (P-cells) in the vermis of the oculomotor cerebellum, lobules VIc and VII, changed their complex spike (CS) discharge during the behavioral adaptation of horizontal saccades. We tested the hypothesis that CS activity would change only when a targeting saccade caused an error in eye position relative to the target, i.e., during the error interval between the primary and corrective saccades. We examined only those P-cells whose simple spike activity exhibited either a burst or pause with saccades in several directions. Approximately 80% of such P-cells exhibited an increase in CS activity during the error interval when the adaptation paradigm imposed horizontal eye-position errors in one direction and a decrease in activity for errors in the other. As adaptation progressed and errors were reduced, there was no consistent change in the CS activity. These data suggest that the CS activity of P-cells in the oculomotor vermis signals the direction but not the magnitude of eye-position error during saccade adaptation. Our results are consistent with cerebellar learning models that have been proposed to explain adaptation of the vestibulo-ocular reflex so similar mechanisms may also underlie plasticity of this precision voluntary oculomotor behavior.

There is general agreement that saccades are guided to their targets by means of a motor error signal, which is produced by a local feedback circuit that calculates the difference between desired saccadic amplitude and an internal copy of actual saccadic amplitude. Although the superior colliculus (SC) is thought to provide the desired saccadic amplitude signal, it is unclear whether the SC resides in the feedback loop. To test this possibility, we injected muscimol into the brain stem region containing omnipause neurons (OPNs) to slow saccades and then determined whether the firing of neurons at different sites in the SC was altered. In 14 experiments, we produced saccadic slowing while simultaneously recording the activity of a single SC neuron. Eleven of the 14 neurons were saccade-related burst neurons (SRBNs), which discharged their most vigorous burst for saccades with an optimal amplitude and direction (optimal vector). The optimal directions for the 11 SRBNs ranged from nearly horizontal to nearly vertical, with optimal amplitudes between 4 and 17°. Although muscimol injections into the OPN region produced little change in the optimal vector, they did increase mean saccade duration by 25 to 192.8% and decrease mean saccade peak velocity by 20.5 to 69.8%. For optimal vector saccades, both the acceleration and deceleration phases increased in duration. However, during 10 of 14 experiments, the duration of deceleration increased as fast as or faster than that of acceleration as saccade duration increased, indicating that most of the increase in duration occurred during the deceleration phase. SRBNs in the SC changed their burst duration and firing rate concomitantly with changes in saccadic duration and velocity, respectively. All SRBNs showed a robust increase in burst duration as saccadic duration increased. Five of 11 SRBNs also exhibited a decrease in burst peak firing rate as saccadic velocity decreased. On average across the neurons, the number of spikes in the burst was constant. There was no consistent change in the discharge of the three SC neurons that did not exhibit bursts with saccades. Our data show that the SC receives feedback from downstream saccade-related neurons about the ongoing saccades. However, the changes in SC firing produced in our study do not suggest that the feedback is involved with producing motor error. Instead, the feedback seems to be involved with regulating the duration of the discharge of SRBNs so that the desired saccadic amplitude signal remains present throughout the saccade.