Rhythms of Hippocampal Function and Memory Deficits After Moderate Prenatal Alcohol Exposure

产前适度饮酒后海马功能节律和记忆缺陷

• 批准号: 10721882
• 负责人: Lilliana May Sanchez
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2025-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10721882
• 关键词: Animal Model; Animals; Behavior; Behavioral; Biological Markers; Blood alcohol level measurement; Cells; Characteristics; Child; Cognitive; Cognitive deficits; Coupling; Development; Doctor of Philosophy; Electrophysiology (science); Environment; Face; Fellowship; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Frequencies; Future; Hippocampus; Human; Immobilization; Impaired cognition; Impairment; Individual; Intervention; Laboratories; Learning; Life; Location; Memory; Memory impairment; Modeling; Morphology; Neurobehavioral Manifestations; Neurobiology; Neurons; Paired-Associate Learning; Performance; Periodicity; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Rattus; Research Personnel; Role; School-Age Population; System; Task Performances; Testing; Thinking; Work; alcohol consumption during pregnancy; alcohol exposure; alcohol research; base; density; experience; neural; neurobiological mechanism; offspring; pre-doctoral; reading comprehension; recruit

PROJECT SUMMARY/ABSTRACT Fetal Alcohol Spectrum Disorders involve morphologic and neurobiological abnormalities in offspring subjected to prenatal alcohol exposure. Although not as well studied as high exposure, moderate prenatal alcohol exposure represents the most common and undetected form in humans. While learning and memory deficits have been well characterized at the behavioral level in humans with Fetal Alcohol Spectrum Disorders and in animal models of moderate prenatal alcohol exposure, few studies have determined the circuit or systems level mechanisms. A complete understanding of the neural bases of memory deficits after moderate prenatal alcohol exposure is needed to ultimately identify treatments that may mitigate impacts later in life. In our previous work, we determined that rats with moderate prenatal alcohol exposure are significantly impaired in learning a task that requires the acquisition of an association between an object and its spatial location, called the object-place paired-associate task. Previous studies have demonstrated that disruption to the hippocampus impairs object-place associations. The hippocampal involvement in object-place learning and memory is critically dependent on synchronized rhythmic activity of hippocampal cell populations occurring at slow and fast frequencies. During active behavior, hippocampal cell activity can be organized by coupling between a slow rhythm called theta and a fast rhythm called gamma. During immobility, hippocampal neural activity is organized within a fast rhythm called a sharp wave-ripple. Theta-gamma coupling, and the expression of sharp wave-ripples, are thought to have a critical role in the encoding and consolidation of hippocampal dependent memories, respectively. Whether moderate prenatal alcohol exposure disrupts hippocampal theta-gamma coupling or characteristics of hippocampal sharp wave-ripples during performance of a learning and memory task has not been experimentally investigated. In two specific aims, we will test the hypotheses that impaired learning and memory after moderate prenatal alcohol exposure is associated with uncoupling of hippocampal theta-gamma rhythms and a disruption in the sharp wave-ripples characteristics and that these alterations to hippocampal rhythmic activity are associated with impairments in object-place learning and memory. The aims of this proposal will significantly advance our understanding of the neurobiological mechanisms of learning and memory deficits after moderate prenatal alcohol exposure.

项目概要/摘要 胎儿酒精谱系障碍涉及后代的形态学和神经生物学异常 遭受产前酒精暴露。尽管没有像高暴露、中等产前暴露那样进行充分研究 酒精暴露是人类最常见且未被发现的形式。在学习和记忆的同时 胎儿酒精谱系障碍患者的行为水平缺陷已得到很好的表征 在产前中度酒精暴露的动物模型中，很少有研究确定了这一回路或 系统级机制。全面了解中度记忆缺陷后的神经基础 需要产前接触酒精才能最终确定可以减轻以后生活影响的治疗方法。在 我们之前的工作中，我们确定产前中度酒精暴露的老鼠会受到显着损害 在学习需要获取物体与其空间位置之间的关联的任务时， 称为对象-地点配对关联任务。先前的研究表明，对 海马体会损害物体与地点的关联。海马参与客体场所学习和 记忆严重依赖于发生在海马细胞群的同步节律活动 慢频率和快频率。在主动行为期间，海马细胞活动可以通过耦合来组织 介于称为 θ 的慢节奏和称为 伽玛的快节奏之间。不动时，海马神经 活动以一种称为尖锐波涟漪的快节奏组织起来。 Theta-gamma 耦合，以及 尖锐的波涟漪的表达，被认为在编码和巩固中具有关键作用 分别是海马依赖性记忆。适度的产前酒精暴露是否会造成干扰 海马 theta-gamma 耦合或表演过程中海马尖锐波波纹的特征 学习和记忆任务的影响尚未经过实验研究。我们将在两个具体目标中测试 假设产前适度饮酒后学习和记忆受损与 海马 theta-gamma 节律的解耦和尖锐波波纹特征的破坏 海马节律活动的这些改变与物体位置的损伤有关 学习和记忆。该提案的目的将极大地增进我们对 产前适度饮酒后学习和记忆缺陷的神经生物学机制。