From Vision to Action: Transforming the brain's decisions into goal-directed motor behavior

现代神经科学的主要挑战之一是对完整大脑中生物信息处理的全面、机械的理解。可以说，所有物种的大脑最基本的功能是做出决定的能力，从广义上讲，大脑中神经活动的分布最终会达到临界状态，这种状态代表了动物在综合感觉信息的基础上执行几种可能行动中的一种的承诺。快速的感知决策通常不依赖于有意识的考虑，而是由专门的大脑回路执行的感觉模式识别和分类过程的结果。一种普遍存在的行为决策是在接近和逃避行为之间，其中行为反应是从两种相互排斥的类别中选择的，例如接近猎物或逃离捕食者，因此这对最大化生存机会至关重要。重要的是，某些刺激属性的分级变化可以触发反应类别之间的切换，为刺激属性的不同范围分配食欲或厌恶值。在脊椎动物的视觉系统中，物体的大小和速度是决定运动物体的食欲或厌恶值的关键刺激属性。中脑皮层下区域，特别是上丘/视觉顶盖的电路，在食欲、目标导向行为和物体回避行为中都起着关键作用，这表明这是刺激分类和感知决策的中心枢纽。然而，刺激分类和反应选择背后的神经元机制尚不清楚。目前，哺乳动物大脑的大小和复杂性使得以足够的分辨率直接监测视觉诱发的整个大脑的活动流变得困难。因此，我建议在斑马鱼模型中研究皮层下决策和反应选择的机制，在该模型中，可以使用整个大脑的光和电生理技术来监测感觉驱动活动的时空动态。本提案的目标是(i)识别视网膜回路中执行刺激分类和反应选择的层和子网络，（ii）了解编码大脑行为决策的神经命令结构，以及（iii）揭示决策过程的结果如何传递给下游运动控制中心的机制。该项目的长期目标是在这种可处理的脊椎动物模型中建立全脑信息处理的综合模型，最终揭示适用于更大规模哺乳动物大脑的功能原理。

One of the key challenges of modern neuroscience is to develop a comprehensive, mechanistic understanding of biological information processing in intact brains. Arguably, the most fundamental function of brains across all species is the capacity to make decisions, in the broad sense that the distribution of neural activity in the brain eventually assumes critical states that represent the commitment of an animal to perform one out of several possible actions contingent on integrated sensory information. Rapid perceptual decisions often do not depend on conscious deliberation, but are the result of sensory pattern recognition and classification processes performed by dedicated brain circuitry. A ubiquitous behavioral decision is that between approach and avoidance behavior, in which the behavioral response is selected from one of two mutually exclusive categories, e.g. to approach a prey or to escape predators, and which is therefore vital to maximize chances of survival. Importantly, graded variation of certain stimulus attributes can trigger a switch between response categories, assigning appetitive or aversive value to different ranges of a stimulus property. In the vertebrate visual system, object size and velocity are stimulus attributes critically determining the appetitive or aversive value of moving objects. Subcortical areas in the midbrain, and in particular circuitry in the superior colliculus/optic tectum, are critically involved in both appetitive, target-directed behavior and in object avoidance behavior, suggesting that this is a central hub for stimulus classification and perceptual decision making. Yet, the neuronal mechanisms underlying stimulus classification and response selection are not well understood. At present the size and complexity of mammalian brains make it difficult to directly monitor visually evoked streams of activity throughout the brain at sufficient resolution. Therefore, I propose to study mechanisms of subcortical decision making and response selection in the zebrafish model in which the spatiotemporal dynamics of sensory driven activity can be monitored using opto- und electrophysiological techniques throughout the brain. The objectives of this proposal are (i) to identify the layers and subnetworks within the retinotectal circuitry that perform stimulus categorization and response selection, (ii) to understand the neural command structure encoding the brain's behavioral decisions, and (iii) to unravel the mechanisms how the outcome of the decision process is relayed to downstream motor control centers. The longterm goal of this program is to build a comprehensive model of whole-brain information processing in this tractable vertebrate model, which could ultimately reveal functional principles applicable to mammalian brains on a larger scale.