ULTRASTRUCTURE AND FUNCTION OF NERVE AND MUSCLE

描述：大脑中每个神经元的活动都受到 许多“慢”神经递质的活动不断到达 其他神经元，这些动作的总和决定了 神经元的兴奋性。这项拨款建议的主要目的是 为了阐明“缓慢”兴奋性和 “慢”抑制性肽递质对脑的作用 神经元Meynert基底核胆碱能神经元和 蓝斑去甲肾上腺素能神经元培养液， 将使用大鼠大脑;培养这些神经元的技术是 1985年首次在PI实验室开发。这些神经元是 乙酰胆碱和去甲肾上腺素在大脑中的主要来源， 人类的这些神经元在阿尔茨海默病中表现出退化。的 项目集中在以下信号转导机制 递质：P物质，神经降压素，促肾上腺皮质激素释放因子， 和生长抑素。据报道，其中一些发射机 降低阿尔茨海默病的发病率。 将特别强调这些发射机如何调制 内向整流钾通道的活性。在许多大脑神经元中， 内向整流钾通道的调节是负责 产生缓慢兴奋性和缓慢抑制性突触电位。 具体的研究项目是：（1）鉴定哪种G蛋白介导了 P物质，神经降压素， 生长抑素和促肾上腺皮质激素释放因子对 K+通道;（2）探讨第二按摩器的作用 （磷脂酶C和蛋白激酶C，环AMP和环AMP- 依赖性蛋白激酶和蛋白磷酸酶）的信号 转导这些递质，（2）调查机制 G蛋白亚基（突变和非突变）的相互作用， 蛋白激酶和磷酸酶与内向整流钾离子通道 by using运用inside-out内-out补丁.膜片钳电生理和 将使用免疫细胞化学。此外，将使用微量注射器 用于进行肽、抗体的细胞内注射， 反义DNA以破坏特定介体的功能 信号转导级联的一部分

DESCRIPTION: The activity of each neuron in the brain is influenced by the actions of many "slow" neurotransmitters constantly arriving from other neurons, and the total sum of these actions determines the excitability of the neuron. The main objective of this grant proposal is to elucidate the physiological mechanisms by which "slow" excitatory and "slow" inhibitory peptide transmitters produce their actions on brain neurons. Cholinergic neurons from the nucleus basalis of Meynert and noradrenergic neurons from the locus coeruleus in culture prepared from the rat brain will be used; the technique for culturing these neurons was first developed in the PI's laboratory in 1985. These neurons are the main source of acetylcholine and noradrenaline in the brain, and in humans these neurons show degeneration in Alzheimer's disease. The projects focus on the signal transduction mechanisms of the following transmitters: substance P, neurotensin, corticotropin-releasing factor, and somatostatin. Some of these transmitters have been reported to be reduced in Alzheimer's disease. Particular emphasis will be placed on how these transmitters modulate the activity of the inward rectifier K+ channel. In many brain neurons, the modulation of the inward rectifier K+channel is responsible for the generation of slow excitatory and slow inhibitory synaptic potentials. The specific projects are: (1) to identify which G protein mediates the signal transduction of the effects of substance P, neurotensin, somatostatin, and corticotropin-releasing factor on the activity of the K+ channels; (2) to investigate the roles of second massagers (phospholipase C and protein kinase C, cyclic AMP and cyclic AMP- dependent protein kinase, and protein phosphatase) in the signal transduction of these transmitters, and (2) to investigate the mechanisms of the interaction of G protein subunits (mutated and non-mutated), protein kinase, and phosphatases with the inward rectifier K+ channels by using inside-out patches. Patch-clamp electrophysiology and immunocytochemistry will be used. In addition, a microinjector will be used to preform intracellular injection of peptides, antibodies, and antisense DNA in order to disrupt the function of a particular mediator of the signal transduction cascades.