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.

项目摘要/摘要 胎儿酒精谱系涉及后代的形态和神经生物学异常 受到产前酒精的暴露。虽然研究不如高暴露，但中等产前 酒精暴露是人类中最常见和未发现的形式。在学习和记忆的同时 缺陷在患有胎儿酒精谱系障碍的人类的行为水平上的表征很好 在中度产前酒精暴露的动物模型中，很少有研究确定电路或 系统级机制。对中等后记忆缺陷的神经底座的完全理解 需要产前酒精暴露才能最终确定可能减轻以后生活影响的治疗方法。在 我们以前的工作，我们确定患有中等产前酒精暴露的大鼠会严重受损 在学习一项任务时，需要获得对象与其空间位置之间的关联 称为对象位置配对任务。先前的研究表明，对 海马会损害对象位置的关联。海马参与对象学习和 记忆严重取决于发生在 缓慢而快速的频率。在主动行为期间，可以通过耦合来组织海马细胞活性 在称为theta的慢节奏和称为伽马的快速节奏之间。在不动时，海马神经 活性是在称为尖锐波 - 纹状体的快速节奏中组织的。 theta-gamma耦合， 尖锐的波浪形表达被认为在编码和巩固中具有关键作用 海马依赖性记忆。中度产前酒精暴露是否会破坏 海马theta-gamma耦合或在性能过程中海马锋利波的特征 学习和记忆任务尚未经过实验研究。在两个具体目标中，我们将测试 中度产前酒精暴露后学习和记忆障碍的假设与 海马theta-gamma节奏的解偶联和尖锐波动特征的破坏 并且这些对海马节奏活动的改变与对象区域的损害有关 学习和记忆。该提案的目的将大大提高我们对 中等产前酒精暴露后学习和记忆缺陷的神经生物学机制。