The overall goal of the proposed research is to understand how the theta rhythm contributes to memory formation. The theta rhythm is an EEG signal recorded from a brain structure at the medial edge of the cortex called the hippocampus, and it reflects rhythmic neuronal activity that appears to be necessary for normal hippocampal function. An abnormally functioning or severely damaged hippocampus leads to deficits in spatial information processing in animals and the loss of the ability to form new memories in humans. The theta rhythm results from synchronized rhythmic inputs to the hippocampus, and knowledge of how these inputs influence hippocampal cellular activity is fundamental to understanding how the hippocampus participates in the formation of new memories. To study the mechanisms of theta rhythm generation, we have developed a new and powerful method of combining microdialysis and electrophysiology in a single experiment in the waking animal. With this technique, it is possible to deliver drugs locally through a microdialysis probe, so that the drug diffuses into a small area of the brain. The addition of electrodes capable of measuring the current source density (CD) within the diffusion area allow us to measure the changes induced by drug application in currents that influence the activity of the population of cells. It is the goal of these experiments to understand the contributions of the neurotransmitters glutamate and GABA to the generation of the theta rhythm.
