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.

初级传入轴突必须准确地投射到其相应的中枢神经系统， 靶向为高度有序的体细胞定位提供模板 在脊椎动物大脑中的表达。 该研究计划将 提供有关这些过程的机制的新信息 通过回答以下问题：1）感觉神经节细胞或 它们的中心目标具有内在的特异性， 准确的初级传入神经支配的大脑在胎儿的生活？ 我们 将从两个方面来解决这个问题。 我们将描述正常的 脊髓初级传入神经支配的发展，以及V， 楔形核和纤细核，使用亲脂性染料。 如果外围 信息是必要的有序初级传入神经支配的 在中枢神经系统中，感觉神经节细胞必须到达它们的 在有序的中心投影发展之前的外围目标。 在第二系列体外实验中，我们将收获V神经节和 和背根神经节（DRG）细胞之前，他们在一个时代， 使它们的外周或中枢靶神经受支配并将它们共培养 “处女”脑干组织 如果不是初级传入神经元， 它们的中心目标是本质上明确的、适当的首要目标， 传入投射应该在体外形成。 2)是否与 外围设备为asons提供了一个信号，允许他们选择 适当的中央目标？ 如果外围衍生信息 有必要和足够的适当针对性的中央小学 传入投射，消除存在的时间和空间因素 在体内不应引起初级传入特异性的丧失。 相反，剥夺初级传入神经的操纵， 从外围获得的信息应改变其中心目标。 我们 将通过两个实验来解决这个问题。 首先我们要离开 感觉神经节细胞与其外周目标接触并共同 将这些外植体与原始脑干组织一起培养。 如果外围 接触足以指定感觉的中央投射 神经节细胞，这些神经元的轴突会选择适当的 中心目标。 在第二个体内实验中，我们将剥夺腰椎 正常目标的初级传入神经在后肢， 它们支配着这个结构。 如果正常的外围合约 为了精确地定位感觉轴突的中枢， 从这些细胞不应该发展其正常的中央突起。 第三章 初级传入神经支配是否指定了中枢隔室？ 我们将 从两个方面解决这个问题。 我们会切除一些原发性 传入在体内B之前或之后，他们已经达到他们的年龄， 中枢目标，然后确定是否去传入中枢 隔室将接受外来神经支配。 在第二组体外试验中， 在实验中，我们将在他们之前或之后采集脑干的一部分， 受到初级传入神经的正常补充的支配， 然后将它们与适当或不适当的感官 神经节细胞