NEUROGENESIS AND CELL DEATH IN TELECEPHALON

端脑的神经发生和细胞死亡

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/3416749
• 关键词: Aves; axon; brain mapping; cell cell interaction; cell cycle; cell death; cell differentiation; cell migration; cell type; cerebral ventricles; dyes; gene expression; hormone regulation /control mechanism; interneurons; learning; neural plasticity; neurogenesis; neuronal guidance; neurons; phenotype; radiotracer; soma; telencephalon; testosterone

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，鸟类保留了产生新神经元的能力 成年期。 在金丝雀中，有一个端脑歌曲控制区（HVC） 结合了与成人声音可塑性相匹配的新神经元。 这些 细胞从侧脑室壁的出生地迁移 进入 HVC，在那里它们取代其他可能已经死亡的细胞。 一些 新的神经元变成中间神经元，而其他神经元将轴突延伸大约 3 毫米 成为控制学习歌曲的运动通路中的投射神经元。 对成人 HVC 神经发生和神经元死亡的研究可以改善我们的研究 对发声学习、成人神经可塑性和恢复的理解 脑损伤后的功能。 该提案描述了实验 探索; 1）成人连接区分的时间表- 形成的神经元，2）控制表达的可能机制 这些细胞的特定表型，2）新的接触类型 HVC 中的神经元与其他神经元，3）自然的时间过程和数量 发生 HVC 神经元死亡，以及 4) 之间的潜在关系 激素、细胞分裂和细胞死亡。 成年期出生的神经元表达的表型可能是严格的 在细胞分裂时指定或可以稍后通过 神经母细胞和其他细胞之间的相互作用。 早期事件发生在 成年神经元之间细胞类型的分化将是 其特点是用 3H-胸苷（一种细胞出生标记物）治疗鸟类，以及 然后用注射的多个轴突示踪剂逆行标记神经元 3H-胸苷治疗后不同时间进入 HVC 靶点。 这 程序将揭示细胞分化的时间过程并测试 成人形成的 HVC 细胞类型可能是通过 轴突消除过程。 此外，直接的躯体与躯体接触 成人形成的神经元与 HVC 固有的其他细胞将被识别 并将上述方法与串联电池相结合进行定量 1-2 亩切片的重建。 这些方法将允许 评估新的表型之间是否存在关系 神经元和其他细胞紧密接触。 自然发生的细胞死亡的时间和程度将是 通过用活性染料标记 HVC 神经元然后定量来建立 不同存活时间的细胞损失。 内源性激素水平将 在其中一些鸟类中进行操作以测定睾酮是否控制 神经元存活。 这些鸟也将在之前接受 3H-胸苷治疗 牺牲以确定激素水平对细胞生产的影响 在心室区。 细胞类型决定机制及其影响因素的探索 调节细胞分裂/死亡可以提供相关的基本信息 帮助我们了解成人神经发生的功能和控制。