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

项目摘要/摘要 胎儿酒精谱异常涉及子代的形态和神经生物学异常 胎儿期接触酒精。虽然研究不像高暴露、中度产前那样好 酒精暴露是人类最常见、最未被检测到的形式。在学习和记忆的同时 患有胎儿酒精光谱障碍的人在行为水平上的缺陷已经得到了很好的表征 在中度产前酒精暴露的动物模型中，很少有研究确定回路或 系统层面的机制。全面了解中度以上记忆障碍的神经基础 需要产前酒精暴露，以最终确定可能减轻晚年影响的治疗方法。在……里面 在我们之前的工作中，我们确定，出生前适度酒精暴露的大鼠显著受损 在学习需要获取对象与其空间位置之间的关联的任务时， 称为对象-地点配对-关联任务。以前的研究已经证明，对大脑的干扰 海马体损害了物体与位置的联系。海马区参与客体位置学习的实验研究 记忆在很大程度上依赖于海马细胞群在 频率有慢有快。在活跃的行为中，海马细胞的活动可以通过耦合来组织 在一种叫做西塔的慢节奏和一种叫做伽马的快节奏之间。在静止状态下，海马神经 活动是以一种快节奏组织起来的，这种节奏被称为剧烈的波纹。Theta-Gamma耦合，以及 尖锐波纹的表达，被认为在编码和巩固 分别为海马区依赖记忆。适度的产前酒精暴露是否会扰乱 表演时海马theta-Gamma偶联或海马尖波纹特征 对学习和记忆任务的影响还没有进行过实验研究。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受损的假说与 海马theta-Gamma节律的解偶联和尖锐波纹特征的破坏 海马区节律性活动的这些变化与物体位置的损害有关 学习和记忆。这项建议的目的将极大地促进我们对 中度产前酒精暴露后学习和记忆障碍的神经生物学机制。

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.