TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN

PVCN 中胆碱能标记物的瞬时表达

• 批准号: 7850360
• 负责人: Barbara J Morley
• 金额: $ 19.76万
• 依托单位: FATHER FLANAGAN'S BOYS' HOME
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850360
• 关键词: AMPA Receptors; ARHGEF5 gene; Acetylcholine; Acetylcholinesterase; Adult; Affect; Affinity; Age; Agonist; Auditory; Auditory system; Axon; Behavior; Biochemical; Brain; Bungarotoxins; Calcium; Carrier Proteins; Cells; Child; Choline; Choline O-Acetyltransferase; Cholinergic Receptors; Cochlear nucleus; Data; Development; Diffuse; Environment; Enzymes; Event; Extracellular Space; Gene Expression; Glutamate Receptor; Glutamates; Goals; Hearing; Histocytochemistry; Image; In Situ Hybridization; Laboratories; Language Disorders; Light; Link; Literature; Long-Term Effects; Measures; Methods; Microscopic; Minor; Molecular; Mothers; Mutant Strains Mice; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nerve; Nerve Tissue; Neurons; Nicotine; Nicotinic Agonists; Nicotinic Antagonists; Nicotinic Receptors; Octopus; Pathway interactions; Presynaptic Terminals; Proteins; Rattus; Receptor Gene; Regulation; Research Personnel; Rodent; Role; Series; Site; Slice; Smoking; Synapses; System; Testing; Toxin; Vertebral column; Vesicle; Vesicular Transport Proteins; base; cholinergic; cholinergic neuron; deafness; experience; fetal; mRNA Expression; methyllycaconitine; nanoGold; neurochemistry; neuronal cell body; neurotransmission; novel; postnatal; postsynaptic; presynaptic; programs; pup; receptor binding; receptor expression; synaptic function; synaptogenesis; uptake

The pathways and synaptic connections in the brain are established by a finely orchestrated series of neurochemical events. Although central auditory system synapses are modified by experience after the onset of hearing, synaptic connectivity is established before the eighth nerve is responsive to the external environment. There is an emerging literature indicating that some enzymes and proteins with minor roles in neurotransmission in the adult brain have major roles in guiding axons and establishing synapses during development. Acetylcholine (ACh), acetylcholinesterase (AChE) and the a7 nicotinic acetylcholine receptor (nAChR) are among the neurochemicals that regulate synaptic events, including the expression of genes obligatory for mature synapse formation in target neurons. In our laboratory, we have discovered a pathway projecting to the rodent octopus cell region of the posterior ventral cochlear nucleus (PVCN) that transiently expresses AChE and the a? nAChR during the second postnatal week. Ultrastructural studies indicate that few synaptic junctions are present by postnatal day 3, and are abundant by P5. The temporal sequence of the expression of the cholinergic markers, together with electrophysiological data from other laboratories, suggests that ACh and related enzymes and proteins are essential for the maturation of synapses. One of their functions may be to modulate glutamatergic receptor gene expression. Toxins that specifically affect cholinergic receptors, such as nicotine, concentrate in the fetal and postnatal brain in physiologically relevant concentrations. While this would not cause deafness, it could contribute to long-term language deficits. The goal of the proposed studies is to elucidate the cholinergic molecular mechanisms related to the maturation of synapses and regulation of NMDA receptor gene expression in the rodent PVCN. The overall hypothesis is that the diffuse release of ACh regulates NMDA glutamate receptor expression by regulating intracellular calcium through a? nicotinic acetylcholine receptors clustered on postsynaptic sites of PVCN octopus cells. The specific hypotheses are: (1) ACh release is nonvesicular; (2) nAChRs are clustered postsynaptically on octopus cells; ACh (3) a? nAChRs on octopus cells regulate intracellular calcium before, but not after, the onset of hearing; (4) nicotine administration will upregulate NMDA, but not AMPA, receptor gene expression; and (5) ACh, through a7 nAChRs, regulates NMDA glutamate receptor expression.

大脑中的途径和突触连接是由精心策划的一系列精心策划的 神经化学事件。尽管中央听觉系统突触是通过经验修改的 听力的发作，在第八神经对外部的反应之前，建立了突触连通性 环境。有新兴文献表明某些酶和蛋白质在 成人大脑中的神经传递在引导轴突和建立突触中具有重要作用 发展。乙酰胆碱（ACH），乙酰胆碱酯酶（ACHE）和A7烟碱乙酰胆碱受体 （NACHR）是调节突触事件的神经化学物质之一，包括基因的表达 目标神经元中成熟的突触形成的强制性。在我们的实验室中，我们发现了一条途径 投射到后腹侧耳蜗核（PVCN）的啮齿动物章鱼细胞区域 表达疼痛和a？在第二个后周内NACHR。超微结构研究表明 在产后第3天之前，很少有突触连接处出现，并且P5丰富。时间序列 胆碱能标记的表达，以及其他实验室的电生理数据 表明ACH及相关酶和蛋白质对于突触的成熟至关重要。之一 它们的功能可能是调节谷氨酸能受体基因表达。特别影响的毒素 胆碱能受体，例如尼古丁，集中在生理相关的胎儿和产后大脑 浓度。尽管这不会引起耳聋，但它可能导致长期语言缺陷。这 拟议的研究的目的是阐明与 突触的成熟和啮齿动物PVCN中NMDA受体基因表达的调节。总体 假设是ACH的扩散释放通过调节来调节NMDA谷氨酸受体表达 细胞内钙通过A？烟碱乙酰胆碱受体聚集在PVCN的突触后部位 章鱼细胞。特定的假设是：（1）ACH释放是无抗性的； （2）NACHR被聚集 在章鱼细胞上突触后； ach（3）a？章鱼细胞上的NACHR调节细胞内钙之前， 但不在之后，听证会发作； （4）尼古丁给药将上调NMDA，但不会上调AMPA，受体 基因表达； （5）通过A7 NACHRS调节NMDA谷氨酸受体表达。