ACTIONS OF ACETYLCHOLINE ON NEOCORTICAL INTERNEURONS

乙酰胆碱对新皮质中间神经元的作用

• 批准号: 2647493
• 负责人: ZIXIU XIANG
• 金额: $ 3.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2647493
• 关键词: acetylcholine; animal genetic material tag; anticholinergic agent; cholinergic agents; cholinergic receptors; gamma aminobutyrate; immunocytochemistry; interneurons; laboratory rat; neocortex; neuropharmacology; polymerase chain reaction; protein structure function; receptor expression; visual cortex

DESCRIPTION Acetylcholine (ACh) is a neurotransmitter that has powerful modulatory influences on neuronal excitability in the mammalian CNS. In contrast to well-studied excitatory actions of ACh on pyramidal cells, little is known about direct effects of cholinergic receptor activation on neocortical interneurons. To test the hypothesis that various types of interneurons in layer V of rat visual cortex respond to ACh differently due to activation of diverse type of subtypes of cholinergic receptors, whole cell current/voltage clamp recordings from visualized neurons in slices will be used in conjunction with intracellular labeling, extracellular drug application, single-cell PCR, and immunocytochemistry. Specifically, the cholinergic modulation of a membrane potential and input resistance in different types of interneurons will be examined. The involvement of different types or subtypes of ACh receptors will be assessed by (1) application of different agonists and/or antagonists; (2) single-cell PCR targeting of mRNAs coding for nicotinic alpha4 and beta2 subunits; and (3) fluorescent antibody labeling of the nicotinic subunits. The ionic mechanisms underlying the actions of ACh will be determined by analysis of voltage clamp data in conjunction with alterations of ionic concentration. The muscarinic modulation of I/A, I/M and AHP currents in different interneurons will also be investigated. This proposed study will provide new information relevant to functional modulation of cortical inhibition nd cortical information processing. Results will also have implications for neurological disorders, such as epilepsy, where cortical disinhibition is hypothesized to be an important underlying mechanism and Alzheimer's disease, in which functional abnormalities may result, at least in part, from a loss of cortical cholinergic innervation.

描述 乙酰胆碱(ACh)是一种具有强大调节功能的神经递质 对哺乳动物中枢神经系统神经元兴奋性的影响。与之形成鲜明对比的是 ACh对锥体细胞的兴奋作用已被充分研究，但知之甚少 关于胆碱能受体激活对新皮质的直接影响 中间神经元。为了检验不同类型的中间神经元在 大鼠视皮层V层对ACh的不同激活反应 不同类型的胆碱能受体亚型，整个细胞 切片中可视化神经元的电流/电压钳记录将是 与细胞内标记、细胞外药物联合使用 应用、单细胞聚合酶链式反应和免疫细胞化学。具体地说， 膜电位和输入电阻的胆碱能调制 不同类型的中间神经元将被检查。参与其中的 不同类型或亚型的ACh受体将通过(1)进行评估 不同激动剂和/或拮抗剂的应用；(2)单细胞聚合酶链式反应 靶向编码烟碱α4和β2亚单位的mRNAs；以及(3) 烟碱亚单位的荧光抗体标记。《离子》 ACh作用的潜在机制将通过分析 结合离子浓度变化的电压钳位数据。 I/A、I/M和AHP电流在不同温度下的毒鼠碱调制 还将对中间神经元进行研究。这项拟议的研究将提供 与皮层抑制功能调节相关的新信息 和大脑皮层信息处理。结果也将产生影响 对于神经系统疾病，如癫痫，皮质去抑制 被认为是阿尔茨海默氏症的重要潜在机制 疾病，其中功能异常可能导致，至少部分， 由于皮质胆碱能神经的丧失。