Functional metamorphosis of a Drosophila taste circuit motor neuron

动物的大脑由数千到数十亿个神经元组成，这些神经元连接在一起，形成控制感知和行为的功能神经回路。通常，神经元必须改变它们的结构或功能来改变电路的活动。这种重塑塑造了学习、发育或行为的季节性变化，以及对伤害或疾病的反应。尽管最近在神经元重塑的机制方面取得了进展，但完全理解仍然是一个遥远的目标。果蝇、果蝇、黑腹果蝇和其他全变态昆虫(表现出不同的幼虫和成虫阶段)提供了自然界最戏剧性的神经元重塑例子之一。在变态过程中，主要负责爬行和进食的幼虫大脑必须转变为控制飞行、行走、进食和交配的成虫。这一过程涉及到许多神经元重新指定为其新的成年角色。在之前的工作中，我已经确定了一种苍蝇运动神经元，它控制着一种非常特定的成年行为：苍蝇的进食结构，称为喙，向美味的食物延伸。如果没有这种神经元的功能，苍蝇就会表现出一种特有的摄食缺陷：它们无法伸展鼻子的最近端，但仍能继续发起其他摄食运动。运动神经元存在于幼虫和成虫中，并在变态过程中经历广泛的重塑。这包括将其轴突重定向到新形成的成年喙肌，并在其树突茎中扩大十倍以上，该树突接受来自行为回路的输入。我现在提议使用果蝇身上可用的强大遗传工具来操纵这种神经元中的基因功能，并识别与其变态有关的基因。这项研究计划将为神经元重塑和功能行为回路的发展提供基本的新见解。

An animal's brain is composed of thousands to billions of neurons, connected together into functional neural circuits that control perception and behaviour. Often, neurons must alter their structure or function to modify the activity of a circuit. Such remodeling shapes learning, developmental or seasonal changes in behaviour, and the response to injury or disease. Despite recent progress in the mechanisms underlying neuronal remodeling, a complete understanding remains a distant goal. The fruit fly Drosophila melanogaster and other holometabolous insects (those displaying distinct larval and adult stages) offer one of nature's most dramatic examples of neuronal remodeling. During metamorphosis, a larval brain responsible largely for crawling and eating must be transformed to control an adult that flies, walks, feeds, and mates. This process involves the respecification of many neurons into their new adult roles. In previous work, I have identified a fly motor neuron that controls a very specific adult behaviour: extension of the fly's feeding structure, called the proboscis, towards palatable foods. Without the function of this neuron, flies exhibit a characteristic feeding defect: they are unable to extend the most proximal part of the proboscis, yet continue to initiate other feeding movements. The motor neuron is present in both larvae and adults and undergoes extensive remodeling during metamorphosis. This includes retargeting of its axon to a newly formed adult proboscis muscle and a greater than ten-fold expansion in its dendritic arbor, which receives input from behavioural circuits. I now propose to use powerful genetic tools available in Drosophila to manipulate gene function in this neuron and identify genes involved in its metamorphosis. This research program will provide fundamental new insight into the mechanisms underlying neuronal remodeling and the development of functional behavioural circuits.