Systems Mediating Glucocorticoid Influences on Memory Consolidation

这个项目旨在确定糖皮质激素是如何影响大脑调节持久记忆形成的机制的。糖皮质激素是一种在情绪唤醒时从肾上腺皮质释放的压力荷尔蒙。此前的证据表明，糖皮质激素外周给药或直接注射到某些大脑区域可以增强对抑制性回避训练的长期记忆，在这项任务中，大鼠从明亮的隔间走进笔直巷子里的黑暗隔间后，会受到一次足电击。然而，这样的实验并不能确定糖皮质激素的使用是否能增强人们对足部电击发生的地方或电击体验本身的记忆。这项研究计划将使用两阶段抑制性回避范式，在该范式中，大鼠在第一天暴露于抑制性回避装置(即上下文)中，第二天在该装置中给予单一的短暂电击。这一改进的范式使得研究糖皮质激素对记忆的调节影响与相同背景下短暂电击体验对记忆的调节影响不同。因此，这些研究的结果将提供对糖皮质激素调节体验的不同方面的洞察。此外，通过将糖皮质激素应用于不同的大脑区域，它将确定特定大脑区域在调节这些不同体验方面的记忆方面的贡献。由于足部电击体验比暴露在设备本身更能唤起情绪，因此，更多的实验将确定唤醒诱导的去甲肾上腺素能激活的差异是否可能是糖皮质激素对背景或休克记忆的不同影响的基础。这些实验的发现将提供对大脑机制的新理解，这些机制调节了为什么对情绪唤醒的经历的记忆比对情绪中性的经历的记忆更生动、持续时间更长。几名本科生(其中许多人代表少数民族)将积极参与进行实验。

This project is designed to determine how glucocorticoids, a class of stress hormones released from the adrenal cortex during emotional arousal, affect brain mechanisms regulating the formation of lasting memory. Previous evidence has indicated that glucocorticoids given peripherally or administered directly into certain brain regions enhance long-term memory of inhibitory avoidance training, a task in which rats receive a single footshock after stepping from a lighted compartment into a darkened compartment in a straight alley. However, such experiments could not determine whether the glucocorticoid administration enhances memory of the place where it received the footshock or of the shock experience itself. This research program will use a two-phase inhibitory avoidance paradigm in which rats will be exposed to the inhibitory avoidance apparatus (i.e., context) on one day and given a single brief shock in the apparatus on a second day. This modified paradigm makes it possible to investigate modulatory influences of glucocorticoids on memory for context separately from modulatory influences on memory for the brief shock experience in the same context. The findings of these studies will thus provide insight into the different aspects of experience modulated by glucocorticoids. Furthermore, by administering glucocorticoids into different brain regions, it will determine the contribution of specific brain regions in modulating memory for these different aspects of experience. As the footshock experience is much more emotionally arousing than exposure to the apparatus per se, additional experiments will determine whether differences in arousal-induced noradrenergic activation may underlie possible differential effects of glucocorticoid administration on memory for context or shock. The findings of these experiments will provide new understanding of the brain mechanisms that regulate why remembrance of emotionally arousing experiences is more vivid and persists longer than remembrance of emotionally neutral experiences. Several undergraduate students (many representing minority groups) will be actively involved in performing the experiments.