The role of cerebellum in dopamine neuron reward prediction error coding

做出和评估预测是大脑功能的一个基本特征。所有的动物都从经验中学习，以优化它们的生存行为，但我们不知道大脑中的关键“预测节点”如何相互交流，也不知道对话是什么。想想我们熟悉的冰淇淋货车的叮当声，我们的大脑已经通过经验了解到，这种声音表明冰淇淋的供应情况以及冰淇淋的美味程度，指导我们决定接近或避免它。小脑和腹侧被盖区（VTA）是预测的关键枢纽，但直到现在一直被认为是独立的系统。新的证据揭示了从小脑到腹侧被盖区的显著联系，这些联系可以影响寻求奖励的行为，因此1）重新定义了我们对这些系统功能的看法，2）表明预测可能在整个大脑中协调一致。这个建议的目标是提供一个详细的电路级表征的作用，小脑在编码的奖励预测错误的腹侧被盖区。为了实现这一点，我们将首先映射到多巴胺能和非多巴胺能神经元内的腹侧被盖区小脑输入的组织。第二，我们将通过记录奖励预测行为期间投射神经元来定义小脑信号到腹侧被盖区的性质。第三，我们将在行为过程中选择性地破坏这些输入，以确定小脑如何在VTA中形成奖励预测错误编码。这项工作对于发展对大脑中预测编码和奖励处理的综合理解至关重要。我们的研究结果将进一步发展生物学上合理的学习算法，并确定在衰老过程中维持和恢复奖励处理系统的目标。

Making and evaluating predictions is a fundamental feature of brain function. All animals learn from experience to optimize their behaviour for survival, yet we don't know how key 'prediction nodes' in the brain talk to each other, or indeed what the conversation is. Consider the familiar jingle of an ice cream van; our brains have learnt through experience that this sound signals the availability of ice cream and how good the treat will be, guiding our decision to approach, or avoid it. The cerebellum and ventral tegmental area (VTA) are critical hubs for prediction, but until now have been considered as independent systems. New evidence reveals prominent connections from the cerebellum to the VTA that can influence reward-seeking behaviour and thus 1) redefine our view of the function of these systems and 2) indicate that predictions may be coordinated throughout the brain. The goal of this proposal is to provide a detailed circuit-level characterisation of the role of the cerebellum in the encoding of reward prediction error in the VTA. To achieve this, we will first map the organisation of cerebellar input onto dopaminergic and non-dopaminergic neurons within the VTA. Second, we will define the nature of the cerebellar signal to the VTA by recording from projection neurons during reward prediction behaviour. Third, we will selectively disrupt these inputs during behaviour to establish how the cerebellum shapes reward prediction error coding in the VTA. This work is essential to develop an integrated understanding of predictive coding and reward processing in the brain. Our findings will further the development of biologically plausible learning algorithms, and identification of targets for the maintenance and restoration of reward processing systems during ageing.