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Cracking the Cerebellar Code

Final Report Summary - CCC (Cracking the Cerebellar Code)

Different theories on the encoding of neuronal communication exist. According to one theory, neurons encode their message with the frequency of their activity (“rate coding”). Alternatively, neurons could (also) use the exact timing of their activity to encode information (“temporal coding”).
Deciphering the neural code lies at the basis of understanding brain function. In this project, we are elucidating the relative importance of rate vs. temporal coding in the cerebellum, a brain region important for among others motor coordination and learning. In other words, we are cracking the cerebellar code. We have shown that – contrary to what was known before – the cerebellum is composed of spatial and functional domains that can be identified by the expression pattern of the enzyme zebrin II. This pattern provides a framework to investigate the molecular and cellular pathways underlying cerebellar function in learning, timing and execution of movements. We have analysed a number of specific mutant mouse lines – each targeting a specific part of the cerebellar circuitry – and described its impact on neuronal activity, cellular learning rules and motor performance. Most importantly, the learning rules for zebrin-positive and -negative zones are opposite: whereas zebrin-positive zones use potentiation mechanisms, the zebrin-negative zones use depression. In addition, it turn out that these processes have an important bearing on diseases associated with the cerebellum.
Thus, our research highlights the diversity of the cerebellum and shows that this diversity is organized along anatomically defined modules. These modules explain not only the basic activity pattern but also determine the learning rules. In addition to the long-known process of cerebellar LTD, we have provided strong evidence for the behavioural relevance of the opposite process - cerebellar LTP - for procedural learning.