This grant proposal tests the global hypothesis that the cerebellum is the site of both forward and inverse internal models of the arm. Internal models provide for representations of the input-output properties of the motor apparatus or their inverses. A forward model predicts the state of system, either the motor variables or the sensory output, as a consequence of the current state of the arm and the motor commands. An inverse dynamics model transforms the desired trajectory into the torques and forces needed to control the arm. The results of numerous psychophysical studies support the hypothesis that the central nervous system utilizes internal models to control movements. Although widely hypothesized that the cerebellum acquires and stores internal models of the arm, there are few explicit tests of this hypothesis based on single cell recordings. Our recent findings demonstrate that Purkinje cells in the intermediate and lateral zones of the anterior lobe do not signal movement dynamics or muscle activity and therefore, cannot provide the neural substrate for an inverse dynamics model of the arm. Instead, the simple spike discharge of these Purkinje cells encodes arm kinematics, potentially consistent with the output of a forward model that predicts the state of the arm. The first two Specific Aims expand our testing of the hypothesis that the cerebellum is the site of an inverse dynamics model of the arm.
Specific Aim 1 examines whether the discharge of cerebellar nuclear neurons is consistent with the output of an inverse dynamics model of the arm, recording nuclear neurons while imposing viscous and elastic force fields.
Specific Aim 2 addresses whether Purkinje cell discharge is consistent with the output of an inverse dynamics model, if force control or force feedback is critical to task performance. Using kinematic, isometric and haptic tracking, these experiments will test whether the movement parameters signaled by Purkinje cell simple spike discharge is conditional based on the type of control strategy or feedback used to perform the task.
Specific Aims 3 -5 test the hypothesis that Purkinje cells are the output of a forward internal model of the arm.
Specific Aim 3 tests whether Purkinje cell simple spike discharge encodes arm kinematics as opposed to target/cursor motion.
Specific Aim 4 uses a random tracking task to examine whether the discharge of Purkinje cells predicts the upcoming state of the limb and whether the prediction generalizes to reaching movements.
In Specific Aim 5 both random and cued perturbations are used to manipulate both the state of the arm and the motor command to further test the forward internal model hypothesis.
The cerebellum is essential for the production of smooth, coordinated movements. The results from these studies may lead to a better understanding of both normal function and the abnormal processing that occurs in cerebellar disease.
|Lang, Eric J; Apps, Richard; Bengtsson, Fredrik et al. (2017) The Roles of the Olivocerebellar Pathway in Motor Learning and Motor Control. A Consensus Paper. Cerebellum 16:230-252|
|Popa, Laurentiu S; Streng, Martha L; Ebner, Timothy J (2017) Long-Term Predictive and Feedback Encoding of Motor Signals in the Simple Spike Discharge of Purkinje Cells. eNeuro 4:|
|Streng, Martha L; Popa, Laurentiu S; Ebner, Timothy J (2017) Climbing Fibers Control Purkinje Cell Representations of Behavior. J Neurosci 37:1997-2009|
|Popa, Laurentiu S; Streng, Martha L; Hewitt, Angela L et al. (2016) The Errors of Our Ways: Understanding Error Representations in Cerebellar-Dependent Motor Learning. Cerebellum 15:93-103|
|Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J (2015) Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation. J Neurosci 35:1106-24|
|Cramer, Samuel W; Popa, Laurentiu S; Carter, Russell E et al. (2015) Abnormal excitability and episodic low-frequency oscillations in the cerebral cortex of the tottering mouse. J Neurosci 35:5664-79|
|Prosise, Jodi F; Hendrix, Claudia M; Ebner, Timothy J (2015) Joint angles and angular velocities and relevance of eigenvectors during prehension in the monkey. Exp Brain Res 233:339-50|
|Cramer, Samuel W; Gao, Wangcai; Chen, Gang et al. (2013) Reevaluation of the beam and radial hypotheses of parallel fiber action in the cerebellar cortex. J Neurosci 33:11412-24|
|Popa, Laurentiu S; Hewitt, Angela L; Ebner, Timothy J (2013) Purkinje cell simple spike discharge encodes error signals consistent with a forward internal model. Cerebellum 12:331-3|
|Ebner, Timothy J; Wang, Xinming; Gao, Wangcai et al. (2012) Parasagittal zones in the cerebellar cortex differ in excitability, information processing, and synaptic plasticity. Cerebellum 11:418-9|
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