Neural instructive signals in the cerebellum [electronic resource]

An understanding of the neural patterns available to guide plasticity in vivo is needed to bridge our knowledge of synaptic plasticity to its function in learning. I investigated the patterns of neural activity that trigger plasticity in vivo in a simple cerebellum-dependent motor learning task, adaptation of the vestibulo-ocular reflex (VOR), with the specific goal of determining which neurons carry the instructive signals that trigger plasticity in the circuit for the VOR. The VOR stabilizes images on the retina during head turns by using vestibular signals to generate compensatory smooth eye movements in the opposite direction of head motion. Motor learning maintains the accuracy of the VOR by modifying the gain and timing of the reflex whenever retinal image motion is persistently associated with head movements. In the laboratory, motor learning in the VOR can be acutely induced by pairing head movements with motion of a visual stimulus. Two specific hypotheses have been proposed regarding the neural signals that guide motor learning in the VOR. One suggests that learning is guided by the activity of Purkinje cells, the output neurons of the cerebellum[1]. The other hypothesis suggests that learning is guided by climbing fiber input to the Purkinje cells[2-4]. Previous experiments addressing which neurons carry instructive signals have typically used a single training condition for increasing VOR gain and a single training condition for decreasing VOR gain[5, 6]. These two training conditions each elicited Purkinje cell and climbing fiber signals that carried information about the required direction of learning, and since the patterns of neural activity were consistent with both hypotheses, data are needed to provide constraints that could discriminate between the hypotheses. The goal of my research is to provide such constraints by recording the patterns of neural activity present in Purkinje cells and climbing fibers during a broader range of visual-vestibular stimuli that induce motor learning in the VOR. I induced motor learning in the VOR by pairing head movements with complex visual stimuli. These novel behavioral manipulations elicited many different combinations of Purkinje cell and climbing fiber signals, allowing us to evaluate how each of these neural signals contributes to learning. My data demonstrated that neither instructive signals in the climbing fibers nor Purkinje cells are necessary for learning, although either signals appear to be sufficient to support learning. Additionally, the largest changes in VOR gain occurred when both signals were present, suggesting that the changes mediated by Purkinje cell-triggered mechanisms and climbing-fiber triggered mechanisms are additive in their effects at the behavioral level. These findings are evidence that motor learning in the VOR is accomplished by parallel and independent operation of climbing fiber-triggered and Purkinje cell-triggered plasticity mechanisms. If cerebellum dependent motor learning is supported by the parallel and independent operation of plasticity mechanisms, similar motor learning need not be accomplished in a stereotyped fashion, but rather similar motor learning can be achieved by engaging distinct subsets of plasticity mechanisms each under the control of a unique instructive signal.

Advisor: Raymond Jennifer L. primary advisor. Thesis advisor
Huguenard John advisor. Thesis advisor
Knudsen Eric I. advisor. Thesis advisor
Newsome William T. advisor. Thesis advisor