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Calcium Imaging of Cortical and Hippocampal Neurons During Learning and Decision Making

Abstract

Studies of the neural basis of memory and decision making have utilized rats as a model organism for decades. Place cells in the hippocampus were first described fifty years ago, and our understanding of the cellular mechanisms of episodic memory and spatial navigation have been primarily based on the rat as a model organism. Modern calcium imaging techniques now allow researchers to monitor hundreds of cells simultaneously, and this has been a boon to brain research. However, until my first publication, calcium imaging in the freely behaving rat had not been demonstrated, and emerging research using calcium imaging in the mouse hippocampus conflicted with decades of rat literature. An intellectual gap was widening, and it was unclear whether differing results stemmed from differences in species or methodology. Therefore, we sought to apply calcium imaging to the rat to demonstrate its feasibility and utility. The research presented in this dissertation is a demonstration of both my efforts developing rat calcium imaging within the Miniscope open-science project, as well as applying these methods to specific hypotheses. Chapter 2 details our most recent experiment, studying the effect of aversive learning on hippocampal place cells and the role of cholinergic signaling. Chapter 3 summarizes collaborative work on the technical development and imaging capabilities of the Large Field of View miniature microscope utilized in the previous chapter. Chapter 4 presents my first co-authored publication where we demonstrated the first usage of single photon calcium imaging in the freely behaving rat, studying how cortical neurons reflect choice utility during effortful decision making.

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