Imagine reaching for a glass of water. The sequence of actions 'reach, grip, return, tip, and sip' is automatic, but without a cerebellum, such precise actions are impossible. Kinetic tremors, where the limb oscillates around a target, result from cerebellar damage and resemble the behavior of poorly tuned feedback error-driven control systems like a bad thermostat, where sensory readings are too slow to inform the brain that the hand is at its target, resulting in the limb repeatedly over- and under-shooting its target. This deficit suggests that the cerebellum normally computes a predictive signal that bypasses slow feedback to guide movement. Here the neural pathways used to produce anticipatory motor control are tested using novel technological applications to manipulate cerebellar output neurons during reaching movements. The experiments proposed will test this hypothesis using a novel closed-loop reach paradigm using mice as a mammalian model combined with neural recordings. The outcomes will clarify the enigmatic role of the cerebellum in online movement correction. The context of these motor control studies will be taught to veterans groups with an interest in movement assistive technologies.
Imagine reaching for a glass of water. The sequence of actions 'reach, grip, return, tip, and sip' is automatic, but without a cerebellum, such precise actions are impossible. Kinetic tremors, where the limb oscillates around a target, result from cerebellar damage and resemble the behavior of feedback error-driven control systems, where slow sensory feedback results in the limb repeatedly over- and under-shooting its target. This deficit suggests that the cerebellum normally computes a 'forward model', i.e. a prediction of body kinematics, bypassing slow sensory feedback to guide movement. Physiological measurements support this model, where Purkinje neuron activity correlates perfectly with movement kinematics, yet the utility of this encoding is obscure at the level of the cerebellar nuclei, which form the sole output of the cerebellum. This proposal advances the hypothesis that the forward kinematic model of Purkinje neurons is refined in the cerebellar nuclei via convergence with a previously unrecognized corollary discharge afferent that exclusively targets the nuclei. The experiments proposed will test this hypothesis using a novel closed-loop reach paradigm in mice with awake-behaving neural recordings and neuronal branch-specific optogenetic manipulations. The outcomes will clarify the enigmatic role of the cerebellum in online movement correction and advance high-speed machine vision-based closed-loop behavioral paradigms. The context of these motor control studies will be taught to veterans groups with an interest in movement assistive technologies.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
