Neural Basis of Context Learning in a Rat Model of FASD

描述(申请人提供)：大鼠出生后4-9天的酒精暴露会导致海马区锥体细胞显著减少，此外还会导致依赖海马体的任务表现受损。这项拟议的研究将寻求建立这些神经和行为影响之间的因果联系，特别是在较低水平的酒精暴露下。上下文预暴露促进效应(CPFE)为研究新生儿酒精对发育中的海马体的影响提供了一个理想的准备。在CPFE中，学习背景、将背景与休克联系起来、检索行为表达的背景记忆发生在不同的日子，每一天都需要海马体的正常运作。我们之前已经证明，高剂量的乙醇超过PD4-9会扰乱幼年大鼠的CPFE。实验1将通过检测在较低剂量的发育性酒精暴露下的大鼠的表现，进一步探索在这项任务中酒精诱导的缺陷。实验2A将使用免疫组织化学技术，通过检测(未受干扰的)对照组大鼠在CPFE范式的三个阶段海马区的即刻早期基因表达(Fos和Arc蛋白)，来探索CPFE范式中情境恐惧条件反射的分子基础。使用前面实验的行为和免疫组织化学技术，实验2B和2C将分别检查海马体和杏仁核中可能的分子异常如何导致暴露于高于PD4-9的低剂量和高剂量乙醇的大鼠的CPFE行为缺陷。

DESCRIPTION (provided by applicant): Alcohol exposure in the rat over postnatal days (PD) 4-9 causes significant decreases in pyramidal cells in the hippocampus, in addition to causing impaired performance on tasks that depend on the hippocampus. The proposed research will seek to establish a causal link between these neural and behavioral effects, particularly at lower levels of alcohol exposure. The context preexposure facilitation effect (CPFE) offers an ideal preparation to examine the effects of neonatal alcohol on the developing hippocampus. In the CPFE, learning about the context, associating the context with shock, and retrieval of the context memory for behavioral expression occurs on separate days, each of which requires the proper functioning of the hippocampus. We have previously shown that a high binge dose of ethanol over PD4-9 disrupts the CPFE in juvenile rats. Experiment 1 will further explore ethanol-induced deficits during this task by examining the performance of rats subjected to lower doses of developmental ethanol exposure. Experiment 2A will use immunohistochemistry techniques to explore the molecular basis of contextual fear conditioning during the CPFE paradigm by examining immediate early gene expression (Fos & Arc protein) in the hippocampus during the three phases of the CPFE paradigm in (undisturbed) control rats. Using the behavioral and immunohistochemical techniques of the preceding experiments, Experiment 2B and 2C will examine how possible molecular aberrations in the hippocampus and the amygdala, respectively, may contribute to the behavioral deficits in the CPFE seen in rats exposed to a low and high dose of ethanol over PD4-9.