ROLE OF CHOLINERGIC M1 RECEPTOR IN MEMORY AND COGNITION

胆碱能毒蕈碱受体的破坏会导致注意力、记忆获得和记忆巩固方面的一系列严重缺陷。同样，阿尔茨海默病和正常衰老的认知能力下降与胆碱能功能障碍有关。M1受体已成为记忆缺陷药物治疗的焦点，可能是因为它是海马和皮层中分布最广泛的毒蕈碱受体。在这里，我们研究了我们在M1中发现的选择性认知缺陷的相关性。 基因敲除小鼠的认知能力下降。在具体目标1中，我们扩展了M1敲除的认知表型。然后，我们在目标2中将该表型与正常老年小鼠进行比较，以确定年轻的M1敲除小鼠和老年小鼠是否存在任何认知缺陷。最后，在目标3中，我们建立了衰老突变型和野生型M1小鼠的群体。据预测，M1突变体将在衰老中表现出过早的进一步下降。特别是M1杂合缺失，它不产生认知缺陷，可能会开始表现出他们与老化。这些研究将为研究M1受体与衰老认知能力下降的相关性奠定基础。

Disruption of cholinergic muscarinic receptors produces an array of profound deficits in attention, memory acquisition, and memory consolidation. Likewise, cognitive decline in Alzheimer's disease and in normal aging is associated with cholinergic dysfunction. The M1receptor has become a focus of pharmacological treatment for memory deficits, perhaps because it is the most widely distributed muscarinic receptor in the hippocampus and cortex. Here we examine the relevance of selective cognitive deficits we have found in M1 knockout mice to cognitive decline in aging. In specific aim 1, we extend the cognitive phenotype of the M1 knockout. We then compare this phenotype to normal aged mice in aim 2, in order to determine if the young M1knockout and aged mouse share any deficits in cognition. Finally in aim 3, we establish a colony of aging mutant and wildtype M1 mice. It is predicted that M1 mutants will show premature further decline in aging. Specifically the M1 heterozygous deletion, which does not produce cognitive deficits, may begin to exhibit them with aging. These studies will form the basis for an investigation of the relevance of the M1 receptor to cognitive decline in aging.