Molecular mechanisms controlling neuronal circuits for decision-making

决策是在一组两个或多个选项中选择一个行动的过程。导致一项决定的分子、细胞和电路事件仍未完全了解。特别是，我们对发生在不同尺度上的事件之间的因果关系知之甚少。分子信号的亚细胞变化如何诱导控制决策的神经回路的宏观效应？这个项目的目标是通过研究斑马鱼幼虫中指导简单决策的电路来回答这个问题。斑马鱼是一种模式生物，具有小而半透明的大脑，可以使用强大的成像和遗传技术来监测和操纵体内大量神经元的活动。动物经常面临的两个重要决定是：是接近食物来源还是避开潜在的捕食者。动机和内部状态，如恐惧和饥饿，强烈地影响着这种类型的选择。例如，我们之前的研究表明，饥饿的斑马鱼幼虫在寻找食物时会冒更大的风险，接近更多模糊但可能可食用的物体。我们还表明，在神经元水平上，这种调节发生在视觉处理的早期阶段，涉及血清素能系统和下丘脑-垂体-肾间轴，这是一条主要参与应激反应的途径。我们现在想要了解在一个神经元子集中调节神经元兴奋性的分子事件如何调节这些神经元回路的功能。为此，我们计划在斑马鱼中进行一系列行为和功能脑成像研究，这些斑马鱼携带突变，破坏了这些细胞内信号通路之一。此外，我们将研究受这些分子改变影响的神经元活动如何控制接近/避免决策的神经回路。该项目将通过揭示将动物的需求和动机转化为调节行为的分子和神经元事件的机制，从而更好地理解指导决策的神经元回路。

Decision-making is the process to choosing an action among a set of two or more alternatives. The molecular, cellular, and circuit events leading to a decision are still not fully understood. In particular, we know very little about the causal links between events happening at different scales. How do subcellular changes in molecular signaling induce macroscopic effects on neuronal circuits controlling decision-making? The objective of this project is to contribute to answer this question by studying the circuits guiding simple decisions in the larval zebrafish, a model organism with a small and translucent brain which allows to use powerful imaging and genetic techniques to monitor and manipulate the activity of large groups of neurons in vivo. Two important decisions animals often face are whether to approach a food source or avoid potential predators. Motivation and internal states, such as fear and hunger, strongly influence this type of choices. For example, we previously showed that hungry zebrafish larvae take more risks when looking for food, approaching more often ambiguous but possibly edible objects. We also showed that at the neuronal level, this modulation occurs at very early stages of visual processing, and involves the serotonergic system and the hypothalamus-pituitary-interrenal axis, a pathway chiefly involved in responses to stress. We now want to understand how molecular events regulating neuronal excitability in a subset of neurons modulate function of these neuronal circuits. To this end, we plan to carry out a series of behavioral and functional brain imaging studies in zebrafish harboring a mutation disrupting one of these intracellular signaling pathways. Furthermore, we will investigate how activity of neurons affected by these molecular alterations control neuronal circuits underlying approach/avoid decisions. This project will lead to a better understanding of the neuronal circuits guiding decision-making by revealing mechanisms translating the needs and motivation of an animal into the molecular and neuronal events regulating behavior.