The Functional Organization of Excitatory Synaptic Input to Place Cells in the HippocampusPublic
The hippocampus has been identified as a critical structure for supporting spatial memory processes in both humans and animals alike. Many of these processes such as the ability to self-localize in a given environment as well as engage in goal-directed navigation are thought to depend on the location-specific firing of CA1 hippocampal pyramidal neurons called place cells. The position of an environment at which the firing rate of a place cell increases is called its place field and the formation of this field is thought to depend on the integration of spatial inputs from upstream brain regions. While experimental work in vitro has shown that CA1 hippocampal pyramidal neurons are capable of both passive and active forms of synaptic integration, surprisingly little is known about how these inputs are integrated to generate a place cell’s spatially precise activity patterns in vivo. This is largely due the inherent difficulty of obtaining electrical recordings from pyramidal neuron dendrites in awake, behaving animals, a prerequisite for identifying place cells in rodents. Currently, in vivo imaging exists as one of the few techniques available to probe subcellular activity in the behaving animal. Thus, the aim of my dissertation work was to determine the functional and anatomical organization of synaptic input to hippocampal place cells during active navigation behavior using in vivo two-photon imaging of glutamate activity. By investigating the patterns of synaptic activity which underlie place cell firing, it is possible to gain a greater understanding of the how individual neurons process behaviorally-relevant information in the intact brain. Additionally, determining the rules by which dendrites process input under normal conditions will help address how abnormalities in input integration can result in neuropathological disease.
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