ACTIONS OF ACETYLCHOLINE ON NEOCORTICAL INTERNEURONS

描述 乙酰胆碱（Acetylcholine，ACh）是一种神经递质，具有强大的调节作用， 对哺乳动物CNS中神经元兴奋性的影响。相比 ACh对锥体细胞的兴奋作用已被充分研究，但知之甚少 胆碱能受体激活对大脑皮层的直接影响 中间神经元为了验证这一假设，各种类型的中间神经元， 大鼠视皮层V层对乙酰胆碱反应差异 不同类型的胆碱能受体亚型，全细胞 来自切片中可视化神经元的电流/电压钳记录将被 与细胞内标记、细胞外药物 应用、单细胞PCR和免疫细胞化学。具体而言是 膜电位和输入电阻的胆碱能调节 将检查不同类型的中间神经元。的参与 不同类型或亚型的ACh受体将通过（1） 应用不同的激动剂和/或拮抗剂;（2）单细胞PCR 靶向编码烟碱α 4和β 2亚基的mRNA;和（3） 烟碱亚基的荧光抗体标记。离子 乙酰胆碱的作用机制将通过分析 结合离子浓度的变化的电压钳数据。 在不同条件下，I/A，I/M和AHP电流的M. 还将研究中间神经元。这项研究将提供 皮层抑制功能调节的新信息 和皮层信息处理。结果也将产生影响 用于神经系统疾病，如癫痫，其中皮质去抑制 被认为是一种重要的潜在机制， 疾病，其中功能异常可能导致，至少部分， 失去了皮层胆碱能神经支配

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.