Effects of Ethanol on Hippocampal Activity during Learning

点击翻译按钮获取中文摘要

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. PUBLIC HEALTH RELEVANCE: The ability to learn is a vital mental process, and the hippocampus is known to play an essential role in the encoding of experience. Research has demonstrated that damage to the hippocampus produces learning and memory deficits similar to those seen in learning disabilities, age-related memory loss, Alzheimer's disease, alcohol-related amnesic syndromes, and other amnesic syndromes. A better understanding of the mechanisms occurring within the hippocampus that comprise learning would be a fundamental advancement in scientific knowledge and aid in the development of novel therapeutic approaches for the treatment of these conditions.