Functional recovery after induced neuronal death

描述：(摘自申请人的摘要) 神经元的产生、迁移和分化主要局限于 温血脊椎动物的早期发育；然而，神经发生也 在广泛的物种中持续到成年期，其中包括鸣禽，他们 将新神经元整合到控制歌曲的脑区(HVC) 制作。高压病患者自发性神经元替换增加与 歌曲随着细胞的死亡而改变。因此，鸣禽是一个很好的模型。 用于研究自发性成年神经元的功能意义 替换和成人大脑修复。大多数新的HVC神经元成为投射 控制习得歌曲产生的运动通路中的神经元。一个 第二种类型的HVC神经元在成年后不会产生。主导因素 一种细胞类型的招募而不是另一种细胞类型的招募尚不清楚。在……里面 为了解决这个问题，我们最近进行了有针对性的实验 正常转向的投射神经元型的光解性神经元死亡 过度会导致相同类型的补偿性替换。诱导性死亡 正常情况下，未替换的类型不会刺激它们的替换。在青少年中， 后一种类型的死亡增加了可替代类型的招募。这 提示神经元死亡调节神经元的招募，但仅限于 可替代的那种。在消除了可替换的神经元后，宋 在一些鸟类中恶化；行为缺陷是暂时的，随后是 不同程度的恢复，增加了诱导神经元 替换可以恢复习得的行为。 在本应用程序中，我们建议进一步研究 实验导致的脑损伤，随之而来的脑修复和歌唱 行为。具体地说，我们将确定诱导性神经元死亡是如何导致 歌曲恶化以及随后的恢复是如何发生的。我们将解决(1)什么问题 变量控制着歌曲恶化的类型和严重程度，什么是 恶化的时间进程？(2)行为恢复依赖于同样的 在发育过程中指导发声学习的神经基础？(3) 诱导神经元死亡后的行为恢复依赖于神经元 替补？

DESCRIPTION:( from applicant's abstract) Neuron production, migration, and differentiation are mostly restricted to early development in warm-blooded vertebrates; however, neurogenesis also persists into adulthood in a broad range of species, among them songbirds, who incorporate new neurons into a brain region (HVC) that controls song production. Increases in spontaneous neuronal replacement in HVC correlate with song changes and with cell death. Therefore, songbirds are an excellent model for studies on functional significance of spontaneous adult neuronal replacement and adult brain repair. Most new HVC neurons become projection neurons in the motor pathway that controls the production of learned song. A second type of HVC neuron is not produced in adulthood. The factors governing the recruitment of one cell type but not the other are not known. In experiments to address this question, we recently demonstrated that targeted photolytic neuronal death of the projection neuron type that normally turns over results in compensatory replacement of the same type. Induced death of the normally not replaced type did not stimulate their replacement. In juveniles, death of the latter type increased recruitment of the replaceable kind. This suggests that neuronal death regulates the recruitment of neurons but only of the replaceable kind. After elimination of replaceable neurons, song deteriorated in some birds; behavioral deficits were transient and followed by variable degrees of recovery, raising the possibility that induced neuronal replacement can restore a learned behavior. In this application we propose to further investigate the relationship between the experimentally induced brain injury, the ensuing brain repair and song behavior. Specifically, we will determine how induced neuronal death causes song deterioration and how subsequent recovery occurs. We will address (1) What variables govern the type and severity of song deterioration and what is the time course of deterioration? (2) Does behavioral recovery depend on the same neural substrates that guide vocal learning during development? (3) Does behavioral recovery after induction of neuronal death depend on neuronal replacement?