Remediation of Cholinergic Depletion Effects on Cortical Functions with Neurotrophins

用神经营养素修复胆碱能耗竭对皮质功能的影响

• 批准号: 0132981
• 负责人: Paul Herron
• 金额: $ 6.99万
• 依托单位: The University of Tennessee, Memphis - The Health Science Center
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0132981&HistoricalAwards=false
• 关键词: Remediation; Cholinergic; Depletion; Effects; Cortical

Prior studies have show that when the neurotransmitter acetylcholine is reduced significantly in the cortex of the brain, a cascade of effects is observed in physiological and molecular systems that underlie learning and memory. These effects include changes in neural firing rates and in the expression of non-cholinergic neurotransmitters and synaptic proteins. Thus, two possibilities are suggested for the neural basis of memory: that acetylcholine alone may be responsible, or that it acts in concert with non-cholinergic neurotransmitters and synaptic proteins. The purpose of these studies is to determine whether the mechanisms of learning and memory can be preserved when the cascade of effects of non-cholinergic neural systems is prevented after the loss of acetylcholine. Therefore, acetylcholine in the cortex will be selectively removed and non-cholinergic neurotransmitters and synaptic proteins will be preserved by the application of neurotrophins, a class of brain proteins well known for aiding in the maintenance and survival of cortical neurons challenged by unfavorable conditions. Then the capacity of cortical neurons to undergo changes like those that take place in learning and memory will be determined. These studies are important for understanding the physiological and molecular bases of learning and memory.

先前的研究表明，当大脑皮层中的神经递质乙酰胆碱显着减少时，在学习和记忆基础的生理和分子系统中会观察到一系列的效应。 这些影响包括神经放电率以及非胆碱能神经递质和突触蛋白表达的变化。 因此，对于记忆的神经基础提出了两种可能性：乙酰胆碱可能单独起作用，或者它与非胆碱能神经递质和突触蛋白协同作用。 这些研究的目的是确定当乙酰胆碱丧失后非胆碱能神经系统的级联效应被阻止时，学习和记忆的机制是否可以保留。 因此，通过应用神经营养素，皮质中的乙酰胆碱将被选择性去除，非胆碱能神经递质和突触蛋白将被保留，神经营养素是一类大脑蛋白质，众所周知有助于维持和存活受到不利条件挑战的皮质神经元。 然后，皮质神经元经历学习和记忆中发生的变化的能力将被确定。 这些研究对于理解学习和记忆的生理和分子基础非常重要。