Memory encoding and retrieval: Ethanol modulation of theta reset

描述（由申请人提供）：酒精损害导致新记忆初始编码的认知过程。酒精导致的注意力范围的缩小和工作记忆的减缓，导致对新的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称为θ节律的5-92 Hz电生理振荡一直被证明可以协调记忆绑定的刺激信息流入海马体。我们已经观察到，海马θ节律在记忆编码过程中与内嗅皮层同步，在记忆提取过程中与前额叶皮层同步。Theta节律通过重置其振荡活动的相位，将节律锁定在刺激的开始，从而与刺激编码和提取同步。我们以前曾报道过一些可预测的剂量依赖性变化θ节律急性暴露于酒精。节奏不仅减慢，而且减少了θ重置。酒精对记忆编码和刺激信息提取的神经生理学影响尚未得到研究。目前的建议概述了三个实验，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同步来实现这一点。在第一个实验中，一个传统的空间工作记忆的措施，延迟nonmatch位置任务，被用来评估乙醇对θ同步相对于刺激编码和检索的影响。在第二个实验中，一个操作性任务被用来确定最佳参数，以评估乙醇对记忆编码，巩固和提取的影响，这些参数将被用于第三个实验，以确定theta重置对这些记忆过程的作用。这些研究的结果将提供重要的新的神经解剖学，神经生理学和行为学的见解记忆功能已知受到中等剂量的酒精。 公共卫生相关性：在这项研究中，我们正在研究急性乙醇暴露对记忆编码和提取的神经机制的影响。先前的研究结果表明，乙醇对记忆编码的影响比对记忆提取的影响更大。我们提出的初步证据表明，大脑中一种称为theta活动的有节奏的神经活动在不同的大脑区域之间是同步的，这取决于动物是在编码还是检索信息的过程中。有了这个建议，我们将在动物模型中研究低至中等剂量的乙醇对这些记忆编码和检索的神经机制的影响，以确定它们是否可以解释在人类中观察到的已知行为差异，以便更好地了解易受乙醇损害的大脑结构和过程。

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.