Role of cerebellar parallel fibers in saccade accuracy

描述(由申请者提供)：这项研究将测试一个简单、可信和新颖的关于小脑如何使自愿快速眼动(眼跳)准确的建议。我们认为，眼跳的准确性取决于在正确的时间停止眼跳的信号。这种信号穿过小脑中线的轴突，称为平行纤维(p纤维)。这个信号的到达时间，以及因此使眼跳准确的减速开始，是由信号从小脑中的一个地方穿过中线到达另一边的另一个部位所花费的时间来设置的。我们将通过切断与眼跳相关的P纤维来测试这一提议。如果这个想法是正确的，那么病变将：1)取消帮助及时停止眼跳的小脑信号；2)使眼跳减速异常缓慢；3)使眼跳超过目标。初步数据显示，病变导致了所有三种预测的影响。我们建议的一个推论是，大的眼跳在小脑的眼跳部分是横向的，而小的眼跳是在内侧的。这与早先的发现是一致的。我们将使用解剖学追踪来描述来自该区域外侧和内侧部分的连接，以确定这些连接如何导致不同大小的运动。初步数据显示，小脑眼跳部分的外侧和内侧区域有非常不同的连接。描述这一点将告诉我们小脑如何做出不同大小的运动。如果像我们的试验结果一样，这里提出的工作支持我们的建议，那么它将为小脑如何将接收到的眼跳相关信号转换为用于使眼跳准确的信号提供一个基本框架。这项工作还将说明为什么眼跳，以及随后的视力，在切除儿童最常见的脑瘤的手术中会严重受损。这将激励和指导易于实施的治疗和手术修改，以在不损害视力的情况下移除肿瘤。这样的改进可以迅速帮助患者，因为他们不需要其他创新。与公众健康的相关性拟议的工作将解释为什么在切除儿童最常见的脑瘤的手术后，儿童的眼睛运动以及由此导致的视力严重受损。这一解释将激励和指导手术的改进，以便在不损害视力的情况下切除这些肿瘤。此外，这项工作将提供迄今为止最清晰的描述，说明小脑如何将输入转换为使运动(在这种情况下，眼睛运动)准确的信号。

Description (provided by applicant): This research will test a simple, plausible, and novel proposal about how the cerebellum makes voluntary rapid eye movements (saccades) accurate. We propose that saccade accuracy depends on a signal that stops saccades at the right time. This signal travels across the midline of the cerebellum in the axons called parallel fibers (p-fibers). The arrival time of this signal, and consequently the onset of the deceleration that makes saccades accurate, is set by the amount of time it takes the signal to travel from one place in the cerebellum, across the midline, to another part on the other side. We will test this proposal by cutting saccade-related p-fibers. If this idea is right, then the lesion will: 1) abolish the cerebellum signal that helps stop saccades on time; 2) make saccade deceleration abnormally slow; 3) make saccades overshoot their targets. Preliminary data show that the lesion causes all three predicted effects. A corollary of our proposal is that large saccades are represented laterally in the saccade part of the cerebellum and small saccades are represented medially. This is consistent with earlier findings. We will use anatomical tracing to describe the connections from lateral and medial parts of this region to determine how these connections cause movements of different sizes. Preliminary data show that the lateral and medial areas of the saccade part of the cerebellum make very different connections. Describing this will tell us how the cerebellum makes movements of different sizes. If, like our pilot results, the work proposed here supports our proposal, then it will provide a basic framework for how the cerebellum transforms the saccade-related signals that it receives into the signals that it uses to make saccades accurate. This work will also show why saccades, and consequently vision, are badly impaired by surgery to remove the most common brain tumors in children. This will motivate and guide easy-to- implement modifications of treatment and surgery to remove tumors without impairing vision. Such improvements could help patients quickly because they require no other innovations. PUBLIC HEALTH RELEVANCE The proposed work will explain why eye movements, and consequently vision, are badly impaired in children after surgery to remove the most common brain tumor in children. This explanation will motivate and guide improvements in the surgery so that it removes these tumors without impairing vision. In addition, this work will provide the clearest description yet of how the cerebellum transforms input into signals that make movement, in this case eye movement, accurate.