NEUROGENESIS AND CELL DEATH IN TELECEPHALON

端脑的神经发生和细胞死亡

基本信息

批准号：
3416749
负责人：
JOHN R KIRN
金额：
$ 14.11万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-09-30 至 1995-04-30
项目状态：
已结题

项目摘要

Unlike most mammals, birds retain the capacity to generate new neurons in adulthood. In the canary, a telencephalic song control area (HVC) incorporates new neurons in register with adult vocal plasticity. These cells migrate from their birthplace in the walls of the lateral ventricles into HVC, where they replace other cells that presumably have died. Some new neurons become interneurons, while others extend axons roughly 3 mm to become projection neurons in the motor pathway controlling learned song. Studies of adult HVC neurogenesis and neuronal death could improve our understanding of vocal learning , adult neural plasticity, and recovery o function following brain damage. This proposal describes experiments which explore; 1) the timetable of the differentiation of connectivity by adult- formed neurons, 2) possible mechanisms controlling the expression of specific phenotypes by these cells, 2) the types of contacts made by new neurons with others in HVC,3) the time course and amount of naturally occurring HVC neuron death, and 4) the potential relationship between hormones, cell division and cell death. The phenotypes expressed by neurons born in adulthood may be rigidly specified at the time of cell division or could be determined later through interactions between neuroblasts and other cells. Early events in the differentiation of cell type among adult-formed neurons will be characterized by treating birds with 3H-thymidine, a cell birth marker, and then retrogradely labelling neurons with multiple axonal tracers injected into HVC targets at various times after 3H-thymidine treatment. This procedure will reveal the time course for cell differentiation and test for the possibility that adult-formed HVC cell types are determined through a process of axon elimination. Moreover, direct soma-soma contacts made by adult-formed neurons with other cells intrinsic to HVC will be identified and quantified by combining the above methods with serial cell reconstructions from 1-2 mu sections. These methods will permit an assessment of whether there is a relationship between the phenotypes of new neurons and other cells in close contact. The timing and magnitude of naturally occurring cell death will be established by labelling HVC neurons with a vital dye and then quantifying cell loss at various survival times. Endogenous hormone levels will be manipulated in some of these birds to assay whether testosterone controls neuron survival. These birds will also be treated with 3H-thymidine prior to sacrifice to determine the impact of hormone levels on cell production in the ventricular zone. An exploration of the mechanisms which determine cell type and the factors regulating cell division/death could provide basic information of relevance to our understanding of the functions and control of adult neurogenesis.

与大多数哺乳动物不同，鸟类保留产生新神经元的能力成年。在金丝雀中，远程脑歌曲控制区（HVC）将新的神经元与成人声塑性结合在一起。这些细胞从侧心壁的出生地迁移进入HVC，在那里他们取代了其他可能已经死亡的细胞。一些新神经元成为中间神经元，而其他神经元则大约将轴突扩展到3毫米在控制学习的歌曲的电动通路中成为投影神经元。成人HVC神经发生和神经元死亡的研究可以改善我们的了解声带学习，成人神经可塑性和恢复o 大脑损伤后的功能。该建议描述了实验探索; 1）成人连通性差异的时间表形成的神经元，2）控制的机制这些细胞的特定表型，2）新的接触类型 HVC中与其他人的神经元，3）自然的时间和数量发生HVC神经元死亡，4）激素，细胞分裂和细胞死亡。成年后出生的神经元表达的表型可能很严格在细胞分裂时指定，或以后通过神经细胞与其他细胞之间的相互作用。早期事件细胞类型在成人形成的神经元中的分化将是以3H-胸苷，细胞胎记和然后逆行将神经元用多个轴突示踪剂注射 3H-胸腺定治疗后的不同时间进入HVC靶标。这过程将揭示细胞分化的时间过程和测试成人形成的HVC细胞类型的可能性是通过A确定的消除轴突的过程。此外，由将鉴定出具有HVC的其他细胞的成年神经元并通过将上述方法与串行电池组合来量化 1-2个MU部分的重建。这些方法将允许评估新表型之间是否存在关系神经元和其他细胞紧密接触。天然存在的细胞死亡的时间和大小将是通过用重要染料标记HVC神经元建立，然后进行量化各种生存时间的细胞损失。内源激素水平将是在其中一些鸟中操纵，以测定睾丸激素是否控制神经元的生存。这些鸟还将在先前用3H-胸腺定治疗牺牲以确定激素水平对细胞产生的影响在心室区域。探索确定细胞类型的机制和因素调节细胞分区/死亡可以提供相关性的基本信息我们了解成人神经发生功能和控制。