GENETIC APPROACH TO STUDY ACETYLCHOLINE FUNCTIONS

已有大量的研究致力于理解这些功能 前脑乙酰胆碱(ACh)在哺乳动物认知过程中的作用。 然而，许多研究得出的结论都受到了 与药物和药物的固有局限性有关的告诫 损伤正在接近。因此，ACh的具体功能仍然模棱两可。 为了直接了解ACH在学习中的作用，我们将 开发一种有条件的遗传方法，使我们能够消除 来自大脑离散区域的ACh具有时间和空间 精确度。特别是，携带该基因loxP修饰的小鼠 编码胆碱乙酰转移酶(ChAT)将由标准 基因打靶技术。成年纯合子小鼠将被注射 编码Cre重组酶的病毒载体。受感染的神经元将 功能上使他们的聊天基因失活，因此将不再是 能够合成ACh。一旦方法的参数是 结果是，我们将确定基底前脑ACh的丧失是否会改变 无论是基本的行为功能还是认知功能。如果成功，这将是 该系统将具有普遍的适用性，以重新审查许多 乙酰胆碱在哺乳动物中的可能功能。

A great deal of research has been devoted to understanding the functions of forebrain acetylcholine (ACh) in mammalian cognitive processes. However, conclusions from many of the studies have been tempered by caveats related to the inherent limitations of pharmacological and lesion approaches. Thus, specific functions of ACh remain equivocal. In order to look directly at the role of ACh in learning, we will develop a conditional genetic approach which will allow us to eliminate ACh from discrete regions of the brain with spatial and temporal precision. Specifically, mice carrying a loxP modification of the gene encoding choline acetyltransferase (ChAT) will be generated by standard gene targeting techniques. Adult homozygous mice will be administered a viral vector encoding Cre recombinase. Infected neurons will functionally inactivate their ChAT genes, and thus will no longer be able to synthesize ACh. Once the parameters of the methodology are worked out, we will determine if loss of basal forebrain ACh alters either basic behavioral or cognitive functions. If successful, this system will have general applicability for re-examination of many putative functions of ACh in mammals.