ROLE OF CHOLINERGIC M1 RECEPTOR IN MEMORY AND COGNITION

点击翻译按钮获取中文摘要

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.