Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Neurosciences

Language

English (en)

Date of Award

January 2010

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Pablo Blazquez

Abstract

The cerebellar cortex is usually offered up as the prime example of a well-worked out circuit; indeed, its basic neuronal composition and organization has been known for over one hundred years. Yet mysteries still abound about the computations that are performed within its layers, and how these computations contribute to sensation and behavior. This project was an effort to look inside the cerebellar cortical circuit during behavior to see if I could shed some light on the computations being performed. The dissertation is divided into three main sections. In the first, I present the results of preliminary work performed by myself and my colleagues to advance the aims of the project. This included writing software to train squirrel monkeys and control a variety of vestibulo-oculomotor tasks, characterizing the oculomotor behavioral repertoire of the squirrel monkey in comparison to that of the rhesus macaque, and developing two techniques for examining the roles of interneurons in cerebellar processing. In the second, I present the results of a study of one such interneuron, the Golgi cell, which is the main type of inhibitory interneuron that regulates information flow at the input stage of the cerebellar cortex. I recorded Golgi cells in the ventral paraflocculus: VPFL), a region of the cerebellum known to be involved in oculomotor behavior, while squirrel monkeys performed visual, vestibular, and eye movement tasks, and found that the VPFL Golgi cells only carry information from the eye movement pathways. Further, I found that this eye movement information is highly specific, with individual Golgi cells having relatively narrow directional tuning during saccades and pursuit, and only responding within a range of eye positions. This suggests that Golgi cells, through their powerful inhibition of the main path from the input stage to subsequent levels of processing, may serve as spatio-temporal filters of the information arriving at the cerebellar cortex. I delve deeper into this problem in the third section of the dissertation, where I present results from my recordings of mossy fibers and Purkinje cells, the main input and sole output elements, respectively, of the cerebellar cortex. I recorded these elements while the monkeys performed the same tasks as with the Golgi cells, sometimes while simultaneously recording Golgi cells, and examined how their responses compared with the responses of Golgi cells. I found that mossy fibers as a population are more narrowly tuned than Golgi cells, though many individual Golgi cells share a similar tuning width as the mossy fibers, and have different temporal response properties. When individual mossy fibers were recorded near, or simultaneously with, a Golgi cell, the mossy fiber and Golgi cell responses were usually antiphasic. This suggests that the net effect of mossy fiber activity on Golgi cells is inhibitory. When I examined Purkinje cell responses with respect to mossy fibers and Golgi cells, I found that the Purkinje cells generally had broader tuning and more complex, multimodal responses than Golgi cells, consistent with a greater convergence of inputs to Purkinje cells. Finally, when I examined the potential role of Purkinje cell inhibitory inputs coming from molecular layer interneurons by blocking GABA-A receptors while recording Purkinje cells, I found that this inhibition may serve to suppress bursts that are present in the eye movement-related mossy fibers that provide a dominant input to the VPFL. At the end of that chapter I attempt to synthesize these results with the results on the Golgi cells, and in the concluding chapter I suggest additional experiments to further explore the roles of cerebellar cortical interneurons in sensorimotor processing.

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Permanent URL: http://dx.doi.org/10.7936/K7XG9P6T

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