The importance of complex spikes in cerebellar contributions to behaviour.

小脑是大脑的一个主要区域，对协调运动至关重要。在哺乳动物（包括人类）中，它是什么时候受损的？例如，由于中风、遗传疾病或肿瘤？随意的动作，如伸手去抓物体，变得不准确和不适时;平衡被严重破坏;我们学习新的运动技能的能力受损。小脑的内部电路如何确保运动顺利和准确地进行仍然是未知的。被称为浦肯野细胞的神经元是这一功能的核心，因为它们构成了小脑皮层的唯一输出。它们影响小脑核的活动，而小脑核又提供小脑的输出，因此浦肯野细胞改变小脑核活动的方式对于理解小脑如何控制运动至关重要。浦肯野细胞在哺乳动物大脑中是例外的，因为它们释放两种非常不同类型的电脉冲-简单尖峰和复杂尖峰。后者被认为是小脑运作的关键，但它们在运动控制中的作用仍然是一个激烈争论的问题。在试点实验中，我们已经发现，复杂的尖峰可以进一步分为两种不同的类型：尖峰和非尖峰;并且浦肯野细胞在任何给定时间产生的复杂尖峰的类型对同一细胞正在进行的简单尖峰活动有影响。这对小脑信息处理有重要意义，因为这两种类型的复杂尖峰可能会在小脑核团中产生不同的活动模式，提供强大的定时信号，可能是小脑协调运动的基础。使用神经元记录技术，我们将确定两种不同类型的复杂锋电位：i）修改简单锋电位活动，和ii）影响小脑核活动。我们的实验的一个独特之处在于，神经记录将包括动物在仔细控制的条件下进行熟练的伸手抓握运动的复杂尖峰的自然活动模式。因此，该项目的结果将揭示我们执行协调运动能力的基本大脑过程。

The cerebellum is a major region of the brain vital for the coordination of movements. When in mammals (including humans) it is damaged ? e.g. due to stroke, genetic disorders, or tumours ? voluntary movements such as reaching to grasp an object become inaccurate and poorly timed; balance is severely disrupted; and our ability to learn new motor skills is impaired. How the internal circuitry of the cerebellum ensures that movements are performed smoothly and accurately remains unknown. Neurones called Purkinje cells are central to this function because they form the only output of the cerebellar cortex. They influence activity in the cerebellar nuclei, which, in turn, provide the output of the cerebellum, so the way in which cerebellar nuclear activity is modified by Purkinje cells is central to understanding how the cerebellum exerts its control over movement. Purkinje cells are exceptional in the mammalian brain in that they discharge two very different types of electrical impulse - simple spikes and complex spikes. The latter are thought to hold the key to cerebellar operation but their role in movement control remains a hotly debated issue. In pilot experiments we have found that complex spikes can be further categorized into two different types: spiking and non-spiking; and that the type of complex spike generated at any given time by a Purkinje cell has an effect on the on-going simple spike activity of the same cell. This has important implications for cerebellar information processing because the two types of complex spike are likely to produce distinct patterns of activity in the cerebellar nuclei, providing powerful timing signals that could underlie cerebellar contributions to coordinating movement. Using neuronal recording techniques we will determine how the two different types of complex spike: i) modify simple spike activity, and ii) influence cerebellar nuclear activity. One of the unique features of our experiments is that the neural recordings will include the natural activity patterns of complex spikes in action in animals performing a skilled reach-to-grasp movement under carefully controlled conditions. The results from this project will therefore shed light on fundamental brain processes underlying our ability to perform coordinated movements.