COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTION

描述：这项工作旨在理解 神经元切断了与它们制造的一些目标细胞的连接 与正在开发中的联系。实验表明，生物多样性的损失 连接是两国之间长期竞争的结果 不同神经元的突触争相保持与同一靶点的连接 手机。此外，很可能每个轴突的活动都发挥了作用。 在破坏其竞争对手的联系方面。因为神经 活动在导致突触消失的过程中起着重要作用 联系，导致这种损失的机制可能是 体验可以永久性地改变大脑的过程，如 发生在成人的发育和记忆的形成过程中。这 该提案集中在两个简单且可接近的突触区域，这些区域经历了 神经元输入的竞争性丢失--神经肌肉接头和 副交感神经元上的突触。正如之前的工作所表明的那样， 目标细胞可能是输入之间竞争的中介，许多 这些研究试图提供一个更好的理解如何以及为什么 靶细胞在突触丢失期间和之后发生变化。为了获得更多 竞争轴突、神经的分分秒秒行为的详细图像 在活体动物身上标记的终端将被长期跟踪，因为 突触丢失正在发生。来看看神经末梢的活动是否在 突触竞争通过释放神经递质，实验 试图通过局部释放神经递质来模仿竞争 在一个文化菜肴中被提出。最后，看看机制是否 已经描述的肌肉突触丢失的潜在原因是 与副交感神经节的过程相同，实验 其中研究了即将被淘汰的结构和功能的变化 神经节中的突触被提出。这些结果将在 实现对这一关键发展过程的充分理解。 因为学习障碍和记忆障碍很常见，但目前 几乎完全没有理性的对待，那种基本的信息 这项提案旨在提供有关突触变化可能发生的 很有用。

DESCRIPTION: This work is directed at understanding the process whereby neurons sever their connections with some of the target cells they make contact with in development. Experiments indicate that the loss of connections is the consequence of a protracted competition between the synapses of different neurons vying to remain connected to the same target cell. In addition it is likely that the activity of each axon plays a role in destabilizing the connections of its competitors. Because neural activity is instrumental in the process leading to elimination of synaptic connections, the mechanisms underlying this loss may be an important part of the process whereby experience may alters the brain in a permanent way as occurs in development and in the formation of memories in adults. This proposal focuses on two simple and accessible synaptic regions that undergo the competitive loss of neuronal input--the neuromuscular junction and synapses on parasympathetic neurons. As previous work has shown that the target cell may be an intermediary in the competition between inputs, many of these studies attempt to provide a better understanding of how and why the target cell is changed during and after synaptic loss. To get a more detailed picture of the minute by minute behavior of competing axons, nerve terminals labeled in living animals will be followed over long periods as synapse loss is occurring. To see if nerve terminal activity mediates synaptic competition through the release of neurotransmitter, experiments that attempt to mimic competition with localized release of neurotransmitter in a culture dish are proposed. Lastly to see whether the mechanisms underlying the loss of synapses in muscle that has already been described is the same as the process that occurs in parasympathetic ganglia, experiments which study changes in the structure and function of soon-to-be eliminated synapses in ganglia are proposed. These results will be useful in the attainment of a full understanding of this key developmental process. Because learning disorders and memory impairments are common but at present almost entirely without rational treatment, the kind of basic information this proposal aims to provide concerning how synapses change is likely to be useful.