Effects of Ethanol on Hippocampal Activity during Learning

描述（由申请人提供）：海马在将工作记忆编码为长期记忆的过程中起着至关重要的作用，这是学习的一个重要方面。多项研究表明，海马体损伤产生的学习缺陷类似于学习障碍、与年龄相关的记忆丧失、阿尔茨海默病、酒精相关的遗忘综合征和其他遗忘综合征。尽管被广泛研究，神经编码的机制仍然是神秘的。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离开来。因此，一个区分与学习相关的神经活动的模型对于提高我们对海马体的理解是必要的。此外，我们还想知道乙醇是如何通过破坏海马体内的神经活动而产生学习障碍的。利用动物模型，本项目的目的是：1)表征受试者在非空间操作性学习过程中的神经活动；2)通过检查神经单元活动的信息通信速率和相移来研究与学习相关的神经活动；3)研究乙醇对学习的影响。操作性学习过程允许将与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环境中学习新任务并执行先前学习过的任务。为了进一步研究学习过程，信息论将被应用于估计神经元传递的信息量。我们假设，在学习任务中海马中记录的神经元传达的信息量比在先前学习任务中观察到的要高，并且当受试者暴露于乙醇中时，这两个任务中的信息速率都降低了。此外，我们将描述海马θ节律周期内神经单元活动阶段的变化。我们假设，当受试者在操作过程中学习反应时，theta节律的相移会发生在更早的时间，而当受试者暴露于乙醇中时，相移会被打乱。总之，这些目标将为海马体在学习过程中的作用和乙醇对学习的影响提供新的见解。更好的理解也将阐明产生学习缺陷的机制，并将有助于开发旨在减轻器质性或药物性学习缺陷的治疗方法。

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.