Memory encoding and retrieval: Ethanol modulation of theta reset

描述(申请人提供)：酒精损害认知过程，导致新记忆的初始编码。注意范围的缩小和酒精产生的工作记忆的减慢导致了编码新情节记忆细节的能力减弱。在哺乳动物大脑中记录的被称为theta节奏的5-92赫兹电生理振荡一直被证明协调记忆限制的刺激信息流进入海马体。我们观察到，在记忆编码期间，海马theta节律与内嗅皮层同步，在记忆提取期间与前额叶皮质同步。Theta节律与刺激编码和提取同步，通过重置其振荡活动的阶段，将节律锁定在刺激开始时。我们之前已经报道了急性酒精暴露后theta节律的一些可预测的剂量依赖变化。节奏不仅减慢，而且减少了theta重置。在记忆、编码和提取刺激信息方面，酒精的这些神经生理效应还没有被研究过。目前的提案概述了三个实验，旨在调查以下假设：低至中等剂量的酒精(0.25-1.0g/kg)会损害新记忆的编码，但不会损害对已建立记忆的提取，而乙醇通过扰乱负责这些功能的关键结构之间的theta同步来实现这一点。在第一个实验中，使用空间工作记忆的一种传统测量方法--延迟位置不匹配任务来评估乙醇对刺激编码和提取相关的theta同步化的影响。在第二个实验中，操作任务被用来确定评估乙醇对记忆编码、巩固和提取的影响的最佳参数，这些参数将在第三个实验中用于确定theta重置在这些记忆过程中的作用。这些研究的结果将为人们对中等剂量酒精影响记忆功能提供重要的神经解剖学、神经生理学和行为学方面的新见解。 公共卫生相关性：在这项研究中，我们正在研究急性酒精暴露对记忆编码和提取的神经机制的影响。先前的发现表明，酒精对记忆编码的影响比记忆提取的影响更大。我们提出的初步证据表明，大脑中一种名为theta的有节奏的神经活动在不同的大脑区域之间同步，这取决于动物是在编码还是检索信息的过程中。根据这一建议，我们将在动物模型中检查低到中等剂量的乙醇对这些记忆编码和提取的神经机制的影响，以确定它们是否可以解释已在人类中观察到的已知行为差异，以期更好地了解容易受到乙醇损伤的大脑结构和过程。

DESCRIPTION (provided by applicant): Alcohol impairs the cognitive processes that lead to the initial encoding of new memories. The narrowing of the scope of attention and the slowing of working memory produced by alcohol bring about a diminished capacity to encode the details of new episodic memories. The 5-92 Hz electrophysiological oscillation recorded in the mammalian brain called the theta rhythm has consistently been shown to coordinate the flow of memory-bound stimulus information into the hippocampus. We have observed that the hippocampal theta rhythm synchronizes with the entorhinal cortex during memory encoding and with the prefrontal cortex during memory retrieval. The theta rhythm synchronizes with stimulus encoding and retrieval by resetting the phase of its oscillatory activity, locking the rhythm to the onset of stimulus. We have reported previously some predictable dose-dependent changes in the theta rhythm following acute exposure to alcohol. The rhythm not only slows down but diminishes theta reset. These neurophysiological effects of alcohol have not been studied with respect to memory encoding and retrieval of stimulus information. The current proposal outlines three experiments that are designed to investigate the hypotheses that low to moderate doses of alcohol (0.25 - 1.0 g/kg) impair encoding of new memories but do not impair retrieval of established memories, and that ethanol does this by disrupting the synchronization of theta between critical structures responsible for these functions. In the first experiment, a traditional measure of spatial working memory, the delayed nonmatch to position task, is used to assess the effects of ethanol on theta synchronization relative to stimulus encoding and retrieval. In the second experiment, an operant task is used to determine the optimal parameters in which to assess the effects of ethanol on memory encoding, consolidation and retrieval, and these parameters will be used in the third experiment to determine the role of theta resetting on these memory processes. The results from these studies will provide important new neuroanatomical, neurophysiological and behavioral insights into memory functions known to be affected by moderate doses of alcohol. PUBLIC HEALTH RELEVANCE: In this study we are examining the effects of acute ethanol exposure on the neural mechanisms of memory encoding and retrieval. Previous findings have shown that ethanol affects encoding of memory to a greater extent than retrieval of memory. We present preliminary evidence that a type of rhythmic neural activity in the brain called theta activity is synchronized between different brain regions depending on whether an animal is in the process of encoding or retrieving information. With this proposal, we will examine the effects of ethanol at low to moderate doses on these neural mechanisms of memory encoding and retrieval in an animal model to ascertain whether they can account for the known behavioral differences that have been observed in humans with an eye toward better understanding the brain structures and processes that are vulnerable to impairment by ethanol.