ENDOCRINE CONTROL OF ADULT NEURONAL REPLACEMENT

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 在金丝雀中，一个端脑歌曲控制区（HVC） 与成人声音可塑性相匹配的新神经元。 这些 细胞从它们的出生地侧脑室壁迁移 进入HVC，在那里它们取代了其他可能已经死亡的细胞。 一些 新的神经元成为中间神经元，而其他神经元则将轴突延伸约3 mm， 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。 了解发声学习，成人神经可塑性，以及恢复 脑损伤后的功能。 该提案描述了实验， 探索; 1）成人连接分化的时间表- 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 3）HVC中神经元与其他神经元的自然变化过程和数量 发生HVC神经元死亡，和4）之间的潜在关系 激素、细胞分裂和细胞死亡。 在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，或者可以在以后通过 神经母细胞和其他细胞之间的相互作用。 早期事件 成人形成的神经元之间的细胞类型的分化将是 其特征在于用细胞出生标记物3 H-胸苷处理禽类， 然后用多种轴突示踪剂逆行标记神经元， 在3 H-胸苷处理后的不同时间，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细胞类型通过 轴突消失的过程。 此外， 将鉴定具有HVC固有的其他细胞的成人形成的神经元 并通过将上述方法与串联细胞相结合进行定量 1-2亩断面的重建。 这些方法将允许 评估是否有新的表型之间的关系， 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 通过用活体染料标记HVC神经元， 在不同存活时间的细胞损失。 内源性激素水平将 在这些鸟类中进行了一些操作，以测定睾丸激素是否控制了 神经元存活 这些鸡还将在给药前接受3 H-胸苷治疗 牺牲以确定激素水平对细胞产生的影响 在心室区。 探讨决定细胞类型的机制及其影响因素 调节细胞分裂/死亡可以提供相关的基本信息 对我们理解成人神经发生的功能和控制有很大帮助。

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.