Mechanisms of Memory Modulation by Vagus Nerve Stimulation and Arousal

人们普遍认为，有些记忆，如与重要事件有关的记忆，比其他记忆更好地保留。 在记忆储存过程的调节中，一个似乎很重要的因素是与体验相关的唤醒程度。 与中等程度的行为唤醒相关联的事件的记忆往往比与非常低或非常高的唤醒水平相关联的记忆更好地保留。 过去二十年的研究表明，记忆调节是由脑垂体和肾上腺中与唤醒有关的激素介导的。 例如，注射肾上腺素、去甲肾上腺素、促肾上腺皮质激素、加压素、脑啡肽或内啡肽都能调节保持能力。 然而，这些物质都不能自由地穿过血脑屏障来影响大脑中调节记忆储存的活动。 为了解决这个明显的问题，最近的研究表明迷走神经可能是外周唤醒增强记忆的途径。 这些研究表明，在实验室大鼠，subdermic迷走神经切断术减弱记忆的调节作用，这些代理商和迷走神经的电刺激，在中等强度，可以增强记忆的回避任务。 此外，低强度而非高强度的迷走神经刺激可以增强人类受试者的言语学习。 因此，似乎唤醒导致肾上腺和垂体激素的释放，激活外周受体。 然后这些受体启动神经信息，这些信息通过迷走神经到达大脑以调节记忆过程。 目前研究项目的目标是更好地了解迷走神经活动产生的神经事件，这些神经事件改变了记忆存储的强度。 将进行一系列药理学、电生理学和行为学研究。 行为学研究与电生理学研究有关，电生理学研究的重点是描述迷走神经刺激产生的海马反应的变化，并寻找其根本原因。 第一组研究的目标是描述海马体电活动的变化，海马体是一种已知与记忆有关的重要大脑结构，由迷走神经刺激产生。 其他研究将确定增强记忆的药物是否产生类似于迷走神经刺激后观察到的效果，以及迷走神经活动的阻断是否会改变这些反应。 从这些研究中获得的结果应该能更好地理解记忆存储过程调制的大脑机制。

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.