PRIMARY AFFERENT TARGET SELECTION AND INGROWTH

主要传入目标选择和向内生长

• 批准号: 6104714
• 负责人: ROBERT W RHOADES
• 金额: $ 8.91万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104714
• 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; vibrissae

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投射到其相应的中枢 为高度有序的体视症提供模板的靶点 在脊椎动物大脑中的表现。提出的研究将 提供有关这些进程基础机制的新资料 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殊性，这些特性指导着 胎儿时期大脑的准确初级传入神经支配？我们 将通过两种方式解决这个问题。我们将描述正常的 脊髓初级传入神经的发育，V， 使用亲脂染料的楔形和纤细的细胞核。如果是外围设备 信息对于大脑初级传入神经的有序支配是必要的 中枢神经系统，感觉神经节细胞必须到达它们的 在形成有序的中央投影之前的外围靶点。 在第二系列体外实验中，我们将获取两个V神经节 和背根神经节(DRG)细胞 对它们的外周或中枢靶点进行神经支配，并对它们进行共培养 用“处女”脑干组织。如果是初级传入神经元或 他们的中心目标是内在指定的、适当的主要目标 传入投射应该在体外发育。2)与 外围设备向ASON提供信号，允许它们选择 适当的中央目标？如果外围派生的信息是 对适当定向的中心小学来说是必要的和充分的 传入投射，消除存在的时间和空间因素 在体内不应导致初级传入特异性的丧失。 相反，和剥夺初级传入的操纵 外围派生的信息应该会改变他们的中心目标。我们 将在两个实验中解决这个问题。首先，我们要离开 感觉神经节细胞与它们的外周靶点接触 用处女脑干组织培养这些外植体。如果是外围设备 接触足以确定感官的中枢投射 神经节细胞，这些神经元的轴突应该选择适当的 中心目标。在第二个活体实验中，我们将剥夺腰椎 年龄前正常靶在后肢的初级传入 在那里，它们支配着这个结构。如果正常的外围设备合同是 对于感觉轴突的准确中心定位是必要的，这些纤维 这些细胞不应该形成正常的中枢投射。3) 初级传入神经是否指定中央隔室？我们会 用两种方式解决这个问题。我们将消融原始数据的子集 在他们达到年龄之前或之后在体内传入 中枢靶点，然后确定去传入的中枢 隔室将接受外来神经支配。在第二套体外实验中 在实验中，我们将在实验之前或之后采集脑干的部分 已经被它们正常的初级传入神经和 然后将它们与适当或不适当的感官进行共培养 神经节细胞。