Effects of Ethanol on Hippocampal Activity during Learning

描述（由申请人提供）：海马体在将工作记忆编码为长期记忆的过程中起着重要作用，这是学习的一个重要方面。多项研究表明，海马体的损伤会产生类似于学习障碍、年龄相关性记忆丧失、阿尔茨海默病、酒精相关性遗忘综合征和其他遗忘综合征中所见的学习缺陷。虽然被广泛研究，神经编码的机制仍然是个谜。研究单个神经元已被证明有助于更好地理解这一过程。然而，许多研究混淆了学习和行为问题，使得很难将特定于学习的活动分开。出于这个原因，区分与学习相关的神经活动的模型对于促进我们对海马体的理解是必要的。此外，我们有兴趣知道乙醇如何通过扰乱海马体内的神经活动来产生学习缺陷。使用动物模型，本项目的目的是：1）表征神经活动，而受试者响应在一个非空间操作性学习过程中，2）调查与学习相关的神经活动，通过检查的信息通信速率和神经单元活动的相移，和3）调查乙醇管理产生的影响。操作性学习过程允许任务相关的神经活动和非特异性行为效应与学习区分开来，因为受试者在相同的测试设置中学习新任务并执行先前学习的任务。为了进一步研究学习过程，我们将应用信息论来估计神经元传递的信息量。我们假设，在学习任务期间记录在海马体中的神经元所传达的信息量高于在先前学习的任务期间观察到的信息量，并且当受试者暴露于乙醇时，这两个任务期间的信息率降低。此外，我们将表征海马theta节律周期内神经单元活动阶段的变化。我们假设，在θ节律发生相移到较早的时间，因为受试者学会在操作过程中作出反应，并且当受试者暴露于乙醇时，相移被破坏。总之，这些目标将提供新的洞察海马在学习过程中的作用和乙醇对学习的影响。更好的理解也将有助于阐明导致学习缺陷的机制，并有助于开发旨在减轻器质性或药物诱导的学习缺陷的疗法。

DESCRIPTION (provided by applicant): The hippocampus plays an essential role in the process of encoding working memory into long-term memory, an important aspect of learning. Multiple studies demonstrate that damage to the hippocampus produces learning deficits similar to those seen in learning disabilities, age-related memory loss, Alzheimer's disease, alcohol-related amnesic syndromes, and other amnesic syndromes. Although extensively studied, the mechanisms of neural encoding remain mysterious. Examining individual neurons has proven useful in better understanding this process. However, many studies confound learning and behavioral issues, making it hard to dissociate activity specific for learning. For this reason, a model that differentiates neural activity associated with learning is necessary for advancing our understanding of the hippocampus. In addition, we are interested in knowing how ethanol produces learning deficits by disrupting neural activity within the hippocampus. Using an animal model, the objective of this project is to: 1) characterize neural activity while subjects respond n a non-spatial operant learning procedure, 2) investigate the neural activity associated with learning by examining the information communication rate and phase shifts in neural unit activity, and 3) investigate the effects produced by ethanol administration. The operant learning procedure allows for both task-related neural activity and nonspecific behavioral effects to be differentiated from learning, as subject learn a new task and perform a previously learned task within the same test setting. To further examine the process of learning, information theory will be applied to estimate the amount of information being communicated by neurons. We hypothesize that the amount of information communicated by neurons recorded in the hippocampus during a learning task is higher than observed during a previously learned task and that the information rate during both tasks decreases when subjects are exposed to ethanol. Additionally, we will characterize shifts in the phase of neural unit activity within the hippocampal theta rhythm cycle. We hypothesize that a phase shift to an earlier time in the theta rhythm occurs as subjects learn to responds during the operant procedure and that phase shifts are disrupted when subjects are exposed to ethanol. Together, these aims will provide novel insight into the role of the hippocampus during learning and the effects of ethanol on learning. A better understanding will also shed light on the mechanisms responsible for producing deficits in learning, and will aide in the development of therapies aimed at attenuating organic or drug-induced learning deficits.