COMPETITION BETWEEN AXONS AT THE NEUROMUSCULAR JUNCTION

描述：这项工作旨在理解这一过程 神经元切断与它们所形成的一些目标细胞的连接 联系开发中。 实验表明，损失 联系是企业之间长期竞争的结果 不同神经元的突触竞相保持与同一目标的连接 细胞。 此外，每个轴突的活动也可能发挥作用 破坏其竞争对手的关系稳定。 因为神经 活动在导致消除突触的过程中发挥了重要作用 连接，这种损失背后的机制可能是 经验可能永久改变大脑的过程 发生在成人的发育和记忆形成过程中。 这个 提案重点关注两个简单且可访问的突触区域 神经元输入的竞争性损失——神经肌肉接头和 副交感神经元上的突触。 正如之前的工作表明， 靶细胞可能是输入之间竞争的中介，许多 这些研究试图更好地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、神经每分钟行为的详细图片 在活体动物身上贴上标签的终端将被长期跟踪，因为 突触丢失正在发生。 看看神经末梢活动是否介导 通过释放神经递质进行突触竞争，实验 试图通过神经递质的局部释放来模仿竞争 建议在培养皿中。 最后看机制是否完善 已经描述过的肌肉突触丧失的根本原因是 与副交感神经节中发生的过程相同，实验 研究即将被淘汰的结构和功能的变化 提出了神经节中的突触。 这些结果将有助于 充分了解这一关键的发展过程。 因为学习障碍和记忆障碍很常见，但目前 几乎完全没有经过理性的处理，那种基本信息 该提案旨在提供关于突触可能如何变化的信息 有用的。

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.