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

项目总结/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 产前酒精暴露。虽然没有像高暴露，中度产前 酒精暴露是人类最常见和未检测到的形式。在学习和记忆的同时 在患有胎儿酒精谱系障碍的人类中， 在适度产前酒精暴露的动物模型中，很少有研究确定了回路或 系统级机制。完全理解中度记忆障碍的神经基础 产前酒精暴露是必要的，以最终确定治疗，可能减轻影响以后的生活。在 我们先前的工作，我们确定了适度产前酒精暴露的大鼠明显受损， 在学习需要获取对象与其空间位置之间的关联的任务时， 叫做对象-位置配对关联任务。以前的研究表明， 海马体损害了物体与位置的关联。海马参与物体-位置学习， 记忆力非常依赖于海马细胞群的同步节律活动， 慢和快的频率。在主动行为期间，海马细胞活动可以通过耦合来组织， 在慢节奏θ和快节奏γ之间。在不动期间，海马神经元 活动以快节奏组织，称为尖波波纹。Theta-gamma耦合 表达尖锐的波浪涟漪，被认为在编码和巩固的关键作用， 海马依赖性记忆。适度的产前酒精暴露是否会破坏 海马theta-gamma耦合或海马尖波波纹特征 学习和记忆任务还没有实验研究。在两个具体目标中，我们将测试 产前中度酒精暴露后学习和记忆受损的假设与 海马θ-γ节律的解耦和尖波波纹特征的中断 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。这一建议的目的将大大促进我们对 产前中度酒精暴露后学习和记忆缺陷的神经生物学机制

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.