Effects of Ethanol on Hippocampal Activity during Learning

描述(申请人提供)：在将工作记忆编码成长期记忆的过程中，海马体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，海马体受损会产生学习缺陷，类似于学习障碍、年龄相关性记忆力丧失、阿尔茨海默病、酒精相关健忘症和其他健忘症。尽管被广泛研究，但神经编码的机制仍然是个谜。事实证明，研究单个神经元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，很难将特定于学习的活动分开。因此，一个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，我们有兴趣了解乙醇是如何通过扰乱海马体内的神经活动而导致学习障碍的。利用动物模型，本项目的目标是：1)表征受试者在非空间操作性学习过程中做出反应时的神经活动；2)通过检测信息传输率和神经元活动的相移来研究与学习相关的神经活动；3)调查酒精给药产生的影响。操作学习程序允许将与任务相关的神经活动和非特定行为影响与学习区分开来，因为受试者在相同的测试环境中学习新任务和执行先前学习的任务。为了进一步研究学习的过程，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传递的信息量比在先前学习的任务中观察到的要高，当受试者接触乙醇时，两个任务中的信息率都会下降。此外，我们还将描述海马theta节律周期内神经单位活动时相的变化。我们假设，当受试者在操作过程中学习反应时，theta节律中的相移发生在较早的时间，当受试者暴露在乙醇中时，相移被打乱。总而言之，这些目标将为海马体在学习中的作用以及乙醇对学习的影响提供新的见解。更好的理解也将有助于阐明导致学习缺陷的机制，并将有助于开发旨在减轻器质性或药物诱导的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.