Genetics of nematode pharyngeal muscle excitability

过去四年，我们最重要的成就可概括如下：（1）我们 表明蠕虫会根据食物的质量改变它们的行为。它们通过改变食物的营养成分 他们的运动。这种行为是可塑性的，因为它会被过去的经验和饥饿所改变。(2)我们有 研究出了一条饥饿诱导的分子途径，这条途径导致了摄食行为的改变。 我们称之为饥饿途径，在操作上将饥饿定义为满足两个标准的内部状态： （2）它引起摄食和觅食行为的增加。(3)我们 Lave发现了一种类似于脊椎动物饱腹感的新行为。当喂食过量的高质量食物时， 蠕虫（显然）会吃饱：它们停止进食，速度减慢，似乎睡着了。 总之，这些发现使我们深入了解了一个具有重大意义的广泛问题， 4年前我们几乎没有意识到的存在：食欲是如何控制的？很少有普遍的 生物学中的真理，但以下是一个候选人：所有生物体都必须适应食物的质量和数量 在他们的环境中。人类对食物的反应是在高热量食物 稀缺而珍贵在我们这个新颖的、营养丰富的环境中，对食欲的不当控制 从厌食症到目前流行的肥胖症。 我们建议，在延长资助的几年里，继续我们对食欲这一新问题的调查。 ;控制。我们的具体目标是： 目标1：饥饿信号的上游机制。 目标2：饥饿信号的下游影响。 目标1和2关注饥饿信号。咽肌中的核心饥饿信号通路 从毒蕈碱乙酰胆碱受体GAR-3到MAP激酶MPK-1。我们称之为饥饿途径 因为（1）它是由饥饿激活的，（2）它具有生理和行为效应，使饥饿成为可能。 动物来科普。这提出了两个明显的问题：目的1：什么是上游的毒蕈碱受体？ 饥饿是如何激活这条通路的？目标2：MPK-1的下游是什么？如何激活 改变生理和行为的途径 目的3：食物偏好的细胞和分子机制。 目标3将侧重于食物偏好。在这里，我们将集中在一个单一的问题：通过什么细胞和 分子机制是高品质的食物区别于低？基因筛选将识别基因 对食物的偏好。钙成像将测试这一假设，即特定的中间神经元在大脑中。 运动回路对食物质量作出反应。

Our most significant accomplishments in the last four years can be briefly summarized: (1) We have shown that worms alter their behavior depending on food quality. They seek high-quality food by altering their locomotion. This behavior is plastic, in that it is modified by past experience and hunger. (2) We have worked out a molecular pathway that is induced by starvation, and that leads to changed feeding behavior. We call this the hunger pathway, operationally defining hunger as an internal state that satisfies two criteria: ) it is brought on by starvation, and (2) it causes an increase in feeding and food-seeking behavior. (3) We lave found a new behavior that resembles satiety in vertebrates. When fed an excess of high-quality food, worms (apparently) become full: they stop eating, slow down, and appear to fall asleep. Together, these discoveries have given us insight into a broad question of great significance, whose existence we were barely even aware of 4 years ago: how is appetite controlled? There are few universal truths in biology, but the following is a candidate: All organisms must adapt to the quality and quantity of food available in their environment. Human responses to food evolved in an environment where high-calorie food was scarce and precious. In our novel, nutritionally rich environment, improper control of appetite contributes to diseases from anorexia to the current epidemic of obesity. We propose, in the years of extended funding, to continue our investigation of this new problem of appetite ;ontrol. Our specific aims are: Aim 1: Upstream mechanisms in hunger signaling. Aim 2: Downstream effects of hunger signaling. Aims 1 and 2 focus on hunger signaling. The core hunger signaling pathway in pharyngeal muscle extends from the muscarinic acetylcholine receptor GAR-3 to the MAP kinase MPK-1. We call this a hunger pathway because (1) it is activated by starvation, and (2) it has physiological and behavioral effects that allow the animals to cope. This raises two obvious questions: Aim 1:What is upstream of the muscarinic receptor? How is the pathway activated by starvation? Aim 2: What is downstream of MPK-1? How does activation of the pathway change physiology and behavior? Aim 3: Cellular and molecular mechanisms of food preference. Aim 3 will focus on food preference. Here we will focus on a single question: by what cellular and molecular mechanisms is high-quality food distinguished from low? A genetic screen will identify genes necessary for food preference. Calcium imaging will test the hypothesis that specific interneurons in the locomotory circuit respond to food quality.