TRANSIENT EXPRESSION OF CHOLINERGIC MARKERS IN THE PVCN

大脑中的通路和突触连接是由一系列精心编排的 神经化学事件。尽管中枢听觉系统突触在经历了 在第八神经对外部刺激作出反应之前，突触连通性在听力开始时建立 环境。一项新出现的文献表明，一些酶和蛋白质在体内起着次要作用 成人大脑中的神经传递在引导轴突和建立突触方面起着重要作用 发展。乙酰胆碱(ACh)、乙酰胆碱酯酶(AChE)和A7烟碱型乙酰胆碱受体 (NAChR)是调节突触事件的神经化学物质之一，包括基因的表达 对靶神经元中成熟突触的形成是必需的。在我们的实验室里，我们发现了一条 投射到啮齿动物耳蜗后腹核(PVCN)的章鱼细胞区 表示疼痛和a？NAChR在出生后第二周。超微结构研究表明 到出生后第3天，突触连接很少，到出生后第5天，突触连接丰富。的时间序列 胆碱能标志物的表达，以及来自其他实验室的电生理数据， 提示ACh及相关的酶和蛋白质对突触的成熟是必不可少的。其中之一 它们的功能可能是调节谷氨酸受体基因的表达。特定影响的毒素 胆碱能受体，如尼古丁，集中在胎儿和出生后的大脑中，在生理上与 浓度。虽然这不会导致耳聋，但它可能会导致长期的语言缺陷。这个 本研究的目的是阐明与胆碱能相关的分子机制。 啮齿动物PVCN突触成熟及NMDA受体基因表达的调控。整体而言 假设ACh的弥漫释放通过调节NMDA谷氨酸受体的表达来调节 细胞内钙通过一种？烟碱型乙酰胆碱受体聚集在PVCN突触后部位 章鱼细胞。具体的假设是：(1)ACh的释放是非囊泡性的；(2)nAChRs是聚集的 ACh(3)a？章鱼细胞上的nAChRs以前调节细胞内钙离子， 但不是在听力开始后；(4)尼古丁治疗会上调NMDA受体，但不会上调AMPA受体 ACh通过A7nAChRs调节NMDA谷氨酸受体的表达。

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.