Search

Purkinje cell (PC) discharge, the only output of cerebellar cortex, involves 2 types of action potentials, high-frequency simple spikes (SSs) and low-frequency complex spikes (CSs). While there is consensus that SSs convey information needed to optimize movement kinematics, the function of CSs, determined by the PC's climbing fiber input, remains controversial. While initially thought to be specialized in reporting information on motor error for the subsequent amendment of behavior, CSs seem to contribute to other aspects of motor behavior as well. When faced with the bewildering diversity of findings and views unraveled by highly specific tasks, one may wonder if there is just one true function with all the other attributions wrong? Or is the diversity of findings a reflection of distinct pools of PCs, each processing specific streams of information conveyed by climbing fibers? With these questions in mind, we recorded CSs from the monkey oculomotor vermis deploying a repetitive saccade task that entailed sizable motor errors as well as small amplitude saccades, correcting them. We demonstrate that, in addition to carrying error-related information, CSs carry information on the metrics of both primary and small corrective saccades in a time-specific manner, with changes in CS firing probability coupled with changes in CS duration. Furthermore, we also found CS activity that seemed to predict the upcoming events. Hence PCs receive a multiplexed climbing fiber input that merges complementary streams of information on the behavior, separable by the recipient PC because they are staggered in time., Competing Interests: The authors have declared that no competing interests exist.

The cerebellum allows us to rapidly adjust motor behavior to the needs of the situation. It is commonly assumed that cerebellum-based motor learning is guided by the difference between the desired and the actual behavior, i.e., by error information. Not only immediate but also future behavior will benefit from an error because it induces lasting changes of parallel fiber synapses on Purkinje cells (PCs), whose output mediates the behavioral adjustments. Olivary climbing fibers, likewise connecting with PCs, are thought to transport information on instant errors needed for the synaptic modification yet not to contribute to error memory. Here, we report work on monkeys tested in a saccadic learning paradigm that challenges this concept. We demonstrate not only a clear complex spikes (CS) signature of the error at the time of its occurrence but also a reverberation of this signature much later, before a new manifestation of the behavior, suitable to improve it., Competing Interests: The authors have declared that no competing interests exist.

Saccades and smooth pursuit eye movements (SPEM) are two types of goal-directed eye movements whose kinematics differ profoundly, a fact that may have contributed to the notion that the underlying cerebellar substrates are separated. However, it is suggested that some Purkinje cells (PCs) in the oculomotor vermis (OMV) of monkey cerebellum may be involved in both saccades and SPEM, a puzzling finding in view of the different kinematic demands of the two types of eye movements. Such 'dual' OMV PCs might be oddities with little if any functional relevance. On the other hand, they might be representatives of a generic mechanism serving as common ground for saccades and SPEM. In our present study, we found that both saccade- and SPEM-related responses of individual PCs could be predicted well by linear combinations of eye acceleration, velocity and position. The relative weights of the contributions that these three kinematic parameters made depended on the type of eye movement. Whereas in the case of saccades eye position was the most important independent variable, it was velocity in the case of SPEM. This dissociation is in accordance with standard models of saccades and SPEM control which emphasize eye position and velocity respectively as the relevant controlled state variables.

Recent studies have suggested that microsaccades, the small amplitude saccades made during fixation, are precisely controlled. Two lines of evidence suggest that the cerebellum plays a key role not only in improving the accuracy of macrosaccades but also of microsaccades. First, lesions of the fastigial oculomotor regions (FOR) cause horizontal dysmetria of both micro- and macrosaccades. Secondly, our previous work on Purkinje cell simple spikes in the oculomotor vermis (OV) has established qualitatively similar response preferences for these two groups of saccades. In this work, we investigated the control signals for micro- and macrosaccades in the FOR, the target of OV Purkinje cell axons. We found that the same FOR neurons discharged for micro- and macrosaccades. For both groups of saccades, FOR neurons exhibited very similar dependencies of their discharge strength on direction and amplitude and very similar burst onset time differences for ipsi- and contraversive saccades and, in both, response duration reflected saccade duration, at least at the population level. An intriguing characteristic of microsaccade-related responses is that immediate pre-saccadic firing rates decreased with distance to the target center, a pattern that strikingly parallels the eye position dependency of both microsaccade metrics and frequency, which may suggest a potential neural mechanism underlying the role of FOR in fixation. Irrespective of this specific consideration, our study supports the view that microsaccades and macrosaccades share the same cerebellar circuitry and, in general, further strengthens the notion of a microsaccade-macrosaccade continuum., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Microsaccades, the small saccades made when we try to keep the eyes still, were once believed to be inconsequential for vision, but recent studies suggest that they can precisely relocate gaze to tiny visual targets. Because the cerebellum is necessary for motor precision, we investigated whether microsaccades may exploit this neural machinery in monkeys. Almost all vermal Purkinje cells, which provide the eye-related output of the cerebellar cortex, were found to increase or decrease their simple spike firing rate during microsaccades. At both the single-cell and population level, microsaccade-related activity was highly similar to macrosaccade-related activity and we observed a continuous representation of saccade amplitude that spanned both the macrosaccade and microsaccade domains. Our results suggest that the cerebellum's role in fine-tuning eye movements extends even to the oculomotor system's smallest saccades and add to a growing list of observations that call into question the classical categorical distinction between microsaccades and macrosaccades., (Copyright © 2015 the authors 0270-6474/15/353403-09$15.00/0.)

Lesion studies suggest that the oculomotor vermis (OMV) is critical for the initiation of smooth-pursuit eye movements (SPEMs); yet, its specific role has remained elusive. In this study, we tested the hypothesis that vermal Purkinje cells (PCs) may be needed to fine-tune the kinematic description of SPEM initiation. Recording from identified PCs from the monkey OMV, we observed that SPEM-related PCs were characterized by a formidable diversity of response profiles with typically only modest reflection of eye movement kinematics. In contrast, the PC population discharge could be perfectly predicted based on a linear combination of eye acceleration, velocity, and position. This finding is in full accord with a role of the OMV in shaping eye movement kinematics. It, moreover, supports the notion that this shaping action is based on a population code, whose anatomic basis is the convergence of PCs on target neurons in the cerebellar nuclei.

Contemporary theories of the cerebellum hold that the complex spike (CS) fired by cerebellar Purkinje cells (PCs) reports the error signal essential for motor adaptation, i.e., the CS serves as a teacher reducing the performance error. This hypothesis suggests a monotonic relationship between CS modulation and performance error: the modulation of CS responses should be maximal at adaptation onset and turn back to its pre-adaptation state when the error is nulled. An alternative viewpoint based on studies of saccades suggests that the modulation of the CS discharge builds up as performance error decreases, and maximum and stable CS modulation is found after adaptation has been completed (Catz et al. 2005). We wanted to know whether this pattern can be generalized to other forms of motor adaptation. We resorted to smooth-pursuit adaptation (SPA) as an example of cerebellar-dependent adaptation. SPA is induced by increasing or decreasing target velocity during pursuit initiation that leads to a gradual increase or decrease in eye velocity. We trained 2 rhesus monkeys and recorded CS from PC in vermal lobuli VI and VII during SPA. We find that SPA is accompanied by a pattern of CS firing, which at the onset of adaptation, i.e., when the error is large, is not modulated significantly. On the other hand, when initial eye velocity is stably increased or decreased by adaptation, the probability of CS occurrence during pursuit initiation decreases or increases, respectively. Overall, our results deviate from the predictions made by the classical error-coding concept.

The improvement of motor behavior, based on experience, is a form of learning that is critically dependent on the cerebellum. A well studied example of cerebellar motor learning is short-term saccadic adaptation (STSA). In STSA, information on saccadic errors is used to improve future saccades. The information optimizing saccade metrics is conveyed by Purkinje cells simple spikes (PC-SS) because they are the critical input to the premotor circuits for saccades. We recorded PC-SS of monkeys undergoing STSA to reveal the code used for improving behavior. We found that the discharge of individual PC-SS was unable to account for the behavioral changes. The PC-SS population burst (PB), however, exhibited changes that closely paralleled the qualitatively different changes of saccade kinematics associated with gain-increase and gain-decrease STSA, respectively. Gain-increase STSA, characterized by an increase in saccade duration, replicates the relationship between saccade duration and the end of the PB valid for unadapted saccades. In contrast, gain-decrease STSA, which sports normal saccade duration but reduced saccadic velocity, is characterized by a PB that ends well before the adapted saccade. This suggests that the duration of normal as well as gain-increased saccades is determined by appropriately setting the end of PB end. However, the duration of gain-decreased saccades is apparently not modified by the cerebellum because the PB signals ends too early to determine saccade end. In summary, STSA, and most probably cerebellar-dependent learning in general, is based on optimizing the shape of a PC-SS population response.

Background: Cerebellar Purkinje cells (PC) generate two responses: the simple spike (SS), with high firing rates (>100 Hz), and the complex spike (CS), characterized by conspicuously low discharge rates (1-2 Hz). Contemporary theories of cerebellar learning suggest that the CS discharge pattern encodes an error signal that drives changes in SS activity, ultimately related to motor behavior. This then predicts that CS will discharge in relation to the error and at random once the error has been nulled by the new behavior., Results: We tested this hypothesis with saccadic adaptation in macaque monkeys as a model of cerebellar-dependent motor learning. During saccadic adaptation, error information unconsciously changes the endpoint of a saccade prompted by a visual target that shifts its final position during the saccade. We recorded CS from PC of the posterior vermis before, during, and after saccadic adaptation. In clear contradiction to the "error signal" concept, we found that CS occurred at random before adaptation onset, i.e., when the error was maximal, and built up to a specific saccade-related discharge profile during the course of adaptation. This profile became most pronounced at the end of adaptation, i.e., when the error had been nulled., Conclusions: We suggest that CS firing may underlie the stabilization of a learned motor behavior, rather than serving as an electrophysiological correlate of an error.

One of the earliest computational principles attributed to the cerebellum was the measurement of time. This idea was originally suggested on anatomical grounds, and was taken up again to explain some of the deficits in cerebellar patients. The contribution of the cerebellum to eye movements, in contrast, has traditionally been discussed in the context of motor learning. This view has received support from the loss of saccade adaptation, one of the key examples of motor learning, following lesions of the posterior cerebellar vermis. However, the relationship between the properties of saccade-related vermal Purkinje cells and the behavioural deficits that follow lesions is unclear. Here we report results from single-unit recording experiments on monkeys that reconcile the seemingly unrelated concepts of timing and motor learning. We report that, unlike individual Purkinje cells, the population response of larger groups of Purkinje cells gives a precise temporal signature of saccade onset and offset. Thus a vermal population response may help to determine saccade duration. Modifying the time course of the population response by changing the weights of the contributing individual Purkinje cells, discharging at different times relative to the saccade, would directly translate into changes in saccade amplitude.