NEUROGENESIS AND CELL DEATH IN TELECEPHALON

与大多数哺乳动物不同，鸟类保留了在大脑中产生新神经元的能力 成人期。在金丝雀中，一个端脑歌唱控制区(HVC) 结合了与成人发声可塑性注册的新神经元。这些 细胞从它们的出生地迁移到侧脑室的壁上 进入HVC，在那里它们取代其他可能已经死亡的细胞。一些人 新的神经元成为中间神经元，而其他神经元将轴突延长约3毫米至 成为控制习得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 对发声学习、成人神经可塑性和康复的认识 脑损伤后的功能。这份提案描述了一些实验 探索；1)成人连通性分化的时间表- 形成的神经元，2)可能的机制控制的表达 这些细胞的特定表型，2)新的接触类型 HVC中神经元和其他神经元，3)自然刺激的时间进程和数量 发生HVC神经元死亡，以及4)两者之间的潜在关系 荷尔蒙、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 在细胞分裂时指定的，或者可以在以后通过 神经母细胞与其他细胞之间的相互作用。世界上最早的事件 成体形成的神经元之间的细胞类型分化将是 特点是用~H-胸腺嘧啶核苷(一种细胞出生标记)治疗鸟类，以及 然后用多个轴突示踪剂逆行标记神经元 ~3H-胸腺嘧啶核苷处理后不同时间进入HVC靶点。这 程序将揭示细胞分化的时间进程和检测 成体形成的HVC细胞类型是通过 轴突消除的过程。此外，SOMA-SOMA的直接接触由 将识别出具有HVC固有的其他细胞的成体形成的神经元 并将上述方法与串联电池相结合进行了定量 从1-2亩的区段重建。这些方法将允许 新的表型之间是否存在关系的评估 神经元和其他细胞密切接触。 自然发生的细胞死亡的时间和规模将是 通过用一种活性染料标记HVC神经元，然后量化 不同存活时间的细胞丢失。内源性激素水平将是 在其中一些鸟类身上进行操纵，以测试睾丸激素是否控制着 神经元存活。这些鸟还将接受~3H-胸腺嘧啶核苷预先治疗 牺牲以确定激素水平对细胞生产的影响 在脑室区域。 决定细胞类型及其影响因素的机制探讨 调节细胞分裂/死亡可以提供相关的基本信息 有助于我们理解成人神经发生的功能和控制。

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.