Stress effects on the balance between memory systems

描述(由申请人提供)： 这项研究考察了慢性压力对多个记忆系统之间平衡的影响。慢性压力会损害许多任务中的学习和记忆，尽管有一些报告表明，在慢性压力后没有影响或增强了学习。目前的发现表明，不同的记忆系统以一种包括竞争实例的方式相互作用，通常表现为一个系统的损伤或药物失活可以增强对通常与不同神经系统相关的任务的学习。通过使用体内微透析和灵敏的分析程序，可以检测在迷宫中训练大鼠的过程中乙酰胆碱的释放，样本收集的时间只与几次训练试验相匹配。这类研究的发现表明，几个神经系统中乙酰胆碱的释放是训练激活系统程度的一个有用的标志。例如，当大鼠在T型迷宫上训练时，这种迷宫可以通过位置(海马体依赖)或反应(纹状体依赖)溶液学习，训练前和训练期间乙酰胆碱的释放预测了哪只大鼠使用了每种溶液。 这项建议将使用这样的程序来确定慢性应激是否会导致神经系统在学习过程中优先激活的转变，从而损害某些任务的学习，并增强其他任务的学习。此外，这项建议将同时检测在基线和训练反应下，海马体和纹状体中乙酰胆碱的释放，以确定慢性应激是否导致与认知处理变化相关的不同乙酰胆碱释放谱。因此，这些实验的发现可能会为慢性应激后明显不同的行为发现提供基础。更广泛地说，这些发现解决了一个关键问题，即慢性应激是否会导致神经系统之间的平衡发生变化，从而改变面临新问题的大鼠选择的策略。

DESCRIPTION (provided by applicant): This proposal examines the effects of chronic stress on the balance between multiple memory systems. Chronic stress impairs learning and memory on many tasks, though there are some reports of no effect or enhanced learning after chronic stress. Current findings indicate that different memory systems interact in a manner that includes instances of competition, often demonstrated by showing that lesions or pharmacological inactivation of one system can enhance learning of a task typically associated with a different neural system. By using in vivo microdialysis coupled to sensitive assay procedures, it is possible to examine release of acetylcholine during the course of training rats in mazes, with sample collection timed to match only a few training trials. Findings from studies such as these have shown that release of acetylcholine in several neural systems is a useful marker of the extent to which a system is activated by training. For example, when rats are trained on a T-maze that can be learned using either place (hippocampus-dependent) or response (striatum-dependent) solutions, acetylcholine release before and during training predicts which rats use each solution. This proposal will use such procedures to determine whether chronic stress produces a shift in which neural system is preferentially activated during learning, thereby impairing learning of some tasks and enhancing learning of other tasks. In addition, this proposal will examine simultaneously acetylcholine release in the hippocampus and striatum, at baseline and in response to training, to determine whether chronic stress results in different profiles of acetylcholine release associated with changes in cognitive processing. Thus, the findings of these experiments may offer a basis for apparently discrepant behavioral findings after chronic stress. More generally, the findings address the key issue of whether chronic stress results in a change in the balance between neural systems, thereby altering the strategy selected by a rat faced with a new problem to solve.