Robert A. Jensen - US grants

It is generally accepted that some memories, such as those associated with important events, are retained better than others. One factor that appears to be important in the modulation of memory storage processes is the degree of arousal associated with the experience. Memories of events that are associated with moderate degrees of behavioral arousal tend to be retained better than memories associated with either very low or very high levels of arousal. Research over the past two decades has demonstrated that memory modulation is mediated by the presence of hormones from the pituitary and the adrenals that are associated with arousal. For example, injection of epinephrine, norepinephrine, ACTH, vasopressin, enkephalins, or the endorphins all modulate retention performance. However, none of these substances freely crosses the blood brain barrier to influence activity in the brain that mediates memory storage. In an attempt to resolve this apparent problem, recent research suggests that the vagus nerve may be a pathway by which peripheral arousal enhances memory. These studies demonstrated in laboratory rats that subdiaphragmic vagotomy attenuates the memory modulatory effects of some of these agents and that electrical stimulation of the vagus nerve, at a moderate intensity, can enhance memory of an avoidance task. Further, low-, but not high-intensity vagus nerve stimulation can enhance verbal learning in human subjects. Therefore, it appears that arousal results in the release of adrenal and pituitary hormones that activate peripheral receptors. These receptors then initiate neural messages, which travel to the brain via the vagus to modulate mnemonic processes. The goal of the current research project is to gain a better understanding of the neural events produced by activity in the vagus nerve that alters the strength of memory storage. A series of pharmacological, electrophysiological, and behavioral studies will be conducted. The behavioral studies are linked to electrophysiological studies that focus on characterizing changes in hippocampal responses produced by vagus nerve stimulation and a search for their underlying causes. The goal of the first set of studies is to characterize changes in electrical activity in the hippocampus, a brain structure known to be importantly involved in memory, produced by vagus nerve stimulation. Other studies will determine whether pharmacological agents that enhance memory produce effects similar to those seen following vagus nerve stimulation and whether blockade of vagus nerve activity alters these responses. The results obtained from these studies should yield a better understanding of the brain mechanisms that underlie the modulation of memory storage processes.