PRIMARY AFFERENT TARGET SELECTION AND INGROWTH

主要传入目标选择和向内生长

• 批准号: 6238384
• 负责人: ROBERT W RHOADES
• 金额: $ 8.23万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-15 至 1998-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6238384
• 关键词: afferent nerve; brain mapping; brain stem; central neural pathway /tract; denervation; developmental neurobiology; electron microscopy; ganglions; histology; intercellular connection; laboratory rat; mixed tissue /cell culture; nervous system regeneration; neuronal guidance; peripheral nervous system; spinal ganglion; trigeminal nerve

Primary afferent axons must project accurately to their appropriate central targets to provide the template for the highly ordered somatotopic representations in the vertebrate brain. The research proposed will provide new information regarding the mechanisms underlying these proceses by answering the folowing questions: 1) Do sensory ganglioon cells or their central targets possess intrinsic specificities that guide the accurate primary afferent innervation of the brain during fetal life? We will address this question in two ways. We will describe the normal development of the primary afferent innervation of the spinal cord, and V, cuneate, and gracile nuclei using lipophilic dyes. If peripheral information is necessary for the orderly primary afferent innervation of the central nervous system, sensory gandlion cells must reach their peripheral targets prior to the development of ordered central projections. In second series of in vitro experiments, we will harvest both V ganglion and dorsal root ganglion (DRG) cells prior to the a ge at which they innervate either their peripheral or central targets and cocultured them with "virgin" brainstem tissue. If eitehr the primary afferent neurons or their central targets are intrinsically specified, appropriate primary afferent projections should develop in vitro. 2) Does contact with the periphery provide asons with a signal that allows them to select appropriate central targets? If peripherally derived information is necessary and sufficient for appropriately targeted central primary afferent projections, elimination of temporal and spatial factors present in vivo should not cause a loss of primary afferent specificity. Conversely, and manipulation that deprives primary afferents of peripherally derived information should alter their central targeting. We will address this question in two experiments. First, we will leave sensory ganglion cells in contact with their peripheral t argets and co- culture these explants with virgin brainstem tissue. If peripheral contacts are sufficient to specify the central projections of sensory ganglion cells, the axons of these neurons whould select appropriate central targets. In a second in vivo experiment, we will deprive lumbar primary afferents of their normal targets in the hindlimb prior to the a ge at which they innervate this structure. If normal peripheral contracts are necessary fro the accurate central targeting of sensory axons, the fibers from these cells should not develop their normal central projections. 3) Does primary afferent innervation specify central compartments? We will address this question in two ways. We will ablate subsets of primary afferent in vivo b efore or a fter the age at which they have reached their central targets and then determine whether the deafferented central compartments will accept foreign innervation. In a second set of in vitro experiments, we will harvest portions of the brainstem before or after they have been innervated by their normal complement of primary afferents and then co-culture them with either appropriate or inappropriate sensory ganglion cells.

主要传入轴突必须准确地投射到其适当的中央 为高度有序的体型提供模板的目标 脊椎动物大脑中的表示。 提出的研究将 提供有关这些程序基础的机制的新信息 通过回答问题的问题：1）进行感官神经节细胞或 他们的核心目标具有指导的内在特异性 胎儿生活中大脑的准确原发性传入？ 我们 将通过两种方式解决这个问题。 我们将描述正常 脊髓的主要传入神经支配的发展，V，V， 使用亲脂性染料的cuneate和gracile核。 如果外围 信息对于有序的主要传入支配是必需的 中枢神经系统，感觉甘德利翁细胞必须到达其 外围目标在开发有序中央预测之前。 在第二系列的体外实验中，我们将收集两个V神经节 和背根神经节（DRG）细胞之前 支配其外围或中心目标并共培养 带有“处女”脑干组织。 如果Eitehr是主要传入神经元或 它们的中心目标是本质上指定的，适当的主要目标 传入预测应在体外发展。 2）确实与 外围提供的信号使他们可以选择 适当的中央目标？ 如果外围派生的信息是 必要且足够适当针对的中央初级 传入的预测，消除时间和空间因素 体内不应导致主要传入特异性的丧失。 相反，剥夺主要传入的操纵 外围派生的信息应改变其中心定位。 我们 将在两个实验中解决这个问题。 首先，我们将离开 感官神经节细胞与它们的周围T量和共同接触 用维珍脑干组织培养这些外植体。 如果外围 触点足以指定感官的中心预测 神经节细胞，这些神经元的轴突应该选择合适 中央目标。 在第二个体内实验中，我们将剥夺腰 在A GE之前，其正常目标的主要传入 他们支配了这种结构。 如果正常的外围合同是 经过精确的感觉轴突的中央靶向，纤维的中心靶向 这些细胞不应发展其正常的中央预测。 3） 主要传入神经是否指定中央隔室？ 我们将 通过两种方式解决这个问题。 我们将消融主要的子集 在体内的传播或到达他们达到自己的年龄的年龄 中央目标，然后确定是否取消中央 车厢将接受外国神经。 在第二组体外 实验，我们将在它们之前或之后收集部分脑干 由于其主要传入的正常补体和 然后用适当或不适当的感觉共同培养它们 神经节细胞。