Memory encoding and retrieval: Ethanol modulation of theta reset

描述（由申请人提供）：酒精会损害导致新记忆初始编码的认知过程。酒精引起的注意力范围的缩小和工作记忆的减慢导致对新情景记忆细节进行编码的能力减弱。在哺乳动物大脑中记录的5-92赫兹的电生理振荡被称为θ节律，一直被证明可以协调记忆刺激信息流入海马体。我们观察到海马的θ节律在记忆编码时与内嗅皮层同步，在记忆提取时与前额叶皮层同步。θ节奏通过重新设置其振荡活动的阶段与刺激编码和检索同步，将节奏锁定在刺激的开始。我们以前曾报道过急性酒精暴露后theta节律的一些可预测的剂量依赖性变化。节奏不仅减慢，而且减少了θ复位。酒精对刺激信息的记忆编码和提取的这些神经生理作用尚未被研究。目前的提案概述了三个实验，旨在研究低至中等剂量的酒精（0.25 - 1.0 g/kg）会损害新记忆的编码，但不会损害已建立记忆的检索，并且乙醇通过破坏负责这些功能的关键结构之间的θ波同步来实现这一假设。在第一个实验中，我们采用传统的空间工作记忆测量方法——延迟位置不匹配任务，来评估乙醇对刺激编码和检索的θ同步的影响。在第二个实验中，我们使用一个可操作任务来确定评估乙醇对记忆编码、巩固和检索影响的最佳参数，而这些参数将在第三个实验中被用来确定theta重置在这些记忆过程中的作用。这些研究的结果将为中等剂量酒精对记忆功能的影响提供重要的神经解剖学、神经生理学和行为学上的新见解。

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.