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相应的中枢 目标为高度有序的躯体主题提供模板 脊椎动物大脑中的表征。 拟议的研究将 提供有关这些过程背后机制的新信息 通过回答以下问题： 1）感觉神经节细胞或 他们的中心目标具有内在的特殊性，可以指导 胎儿时期大脑的准确初级传入神经支配？ 我们 将通过两种方式解答这个问题。 我们将描述正常情况 脊髓初级传入神经支配的发育，以及V， 使用亲脂性染料刻画楔形核和纤细核。 如果外围 信息对于有序的初级传入神经支配是必要的 在中枢神经系统中，感觉神经节细胞必须到达它们的 在制定有序的中心预测之前先确定外围目标。 在第二系列体外实验中，我们将收获两个 V 神经节 和背根神经节 (DRG) 细胞 神经支配其外围或中心目标并将其共培养 具有“原始”脑干组织。 如果初级传入神经元或 它们的中心目标本质上是明确的、适当的主要目标 传入投射应该在体外形成。 2) 是否与 外围设备向asons提供信号，允许他们选择 适当的中心目标？ 如果外围衍生的信息是 对于适当有针对性的中心小学来说是必要和充分的 传入投射，消除存在的时间和空间因素 体内不应导致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该改变其中心目标。 我们 将通过两个实验来解决这个问题。 首先，我们将离开 感觉神经节细胞与其周围目标和共同接触 用原始脑干组织培养这些外植体。 如果外围 接触足以指定感觉的中心投射 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 在 a ge 之前，后肢正常目标的主要传入神经 他们支配这个结构。 如果正常的外围合约是 感觉轴突的精确中央定位所必需的，纤维 这些细胞不应形成其正常的中心投影。 3） 初级传入神经支配是否指定中央区室？ 我们将 从两个方面来回答这个问题。 我们将消除主要的子集 在他们达到其年龄之前或之后体内传入 中枢目标，然后确定中枢是否传入迟钝 隔室将接受外来神经支配。 在第二组体外实验中 实验中，我们将在它们之前或之后收获部分脑干 受到初级传入神经的正常补充的神经支配 然后将它们与适当或不适当的感官共培养 神经节细胞。