Title

Function of Long-Term Depression in Purkinje Cells to Regulate Excitability to a New Equilibrium

Date of Award

2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Huo Lu, PhD

Second Advisor

Richard E White, PhD

Third Advisor

Abigail Hielscher, PhD

Fourth Advisor

Brian Matayoshi, PhD

Abstract

Traditionally, the function of the cerebellum has been thought to be associated with motor control or motor learning. Early studies have shown that cerebellar plasticity plays an important role in cerebellar motor learning. However, a recent study using mutant mice lacking parallel fiber-Purkinje cell long-term depression (LTD) suggested that this specific LTD is not fundamental for motor learning. Therefore, cerebellar plasticity including LTD may have other functions in the cerebellum. We hypothesize that cerebellar plasticity modifies the excitability of Purkinje cells to maintain homeostasis. To test the hypothesis, whole-cell patch clamp recordings were performed on Purkinje cells using neonatal rat cerebellar slices. Tetanus stimulation (1 Hz of train stimulation: 50 Hz, 20 ms interstimulus interval) was delivered to the parallel fibers in the molecular layer. From all the Purkinje cells that were recorded, 4 cells displayed LTD, 7 demonstrated long-term potentiation (LTP), and 9 cells showed no plastic changes. The excitability of the Purkinje cells was measured by number of action potentials generated using positive current injections (0.1, 0.3 and 0.5 nA, 500 ms). In general, the results demonstrated that the excitability decreased after the tetanic stimulation (p = 0.021) for all types of synaptic plasticity. A further study with an improved method of testing the cell excitability is needed.

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