Cerebellar Role in Predictive Control of Eye Velocity Initiation and Termination

Predictive motor control is essential to achieve rapid and precise motor action in all vertebrates. Visuomotor transformations have been a popular model system to study the underlying neural mechanisms, in particular, the role of the cerebellum in both predictive and gain adaptations. In all species, large-field visual motion produces an involuntary conjugate ocular movement facilitating gaze stabilization called the optokinetic response. Gain adaptation can be induced by prolonged optokinetic visual stimulation; and if the visual stimulation is temporally periodic, predictive behavior emerges. Two predictive timing components were identifiable in this behavior. The first was prediction of stimulus initiation (when to move) and the other was stimulus termination (when to stop). We designed visual training that allowed us to evaluate initiation and termination independently that included the recording of cerebellar activity followed by acute and chronic cerebellar removal in goldfish of both sexes. We found that initiation and termination predictions were present in the cerebellum and more robust than conflicting visual sensory signals. Each prediction could be acquired independently, and both the acquisition and maintenance of each component were cerebellar-dependent. Subsequent analysis of the neuronal connectivity strongly supports the hypothesis that the acquired eye velocity behaviors were dependent on feedforward velocity buildup signals from the brainstem, but the adaptive timing mechanism itself originates within the circuitry of the cerebellum.SIGNIFICANCE STATEMENT Predictive and rapid motor control is essential in our daily life, such as in the playing of musical instruments or sports. The current work evaluates timing of a visuomotor behavior shown to be similar in humans as well as goldfish. Given the latter species' known brainstem cerebellar neuronal connectivity and experimental advantage, it was possible to demonstrate the cerebellum to be necessary for acquisition and maintenance of both the initiation and termination components of when to move and to stop. All evidence in this study points to the adaptive predictive control site to lie within the cerebellar circuitry.