Genetics of nematode pharyngeal muscle excitability

描述（由申请人提供）：本研究的长期目标是了解动物行为的遗传基础。方法是研究秀丽隐杆线虫咽部产生摄食行为的可兴奋细胞、神经元和肌肉的功能。在这个资助期间，我们将研究喂养行为的可塑性。需要检验的假设有：假设1。蠕虫会评估食物的质量。假设2。蠕虫通过比较当前食物的质量和过去的经验来决定是否寻找新的食物。假设3。在两种食物的条件下，蠕虫学会识别并偏爱质量更高的食物。假设4。咽部毒蕈碱乙酰胆碱受体通过激活MAP激酶MPK-1的信号转导途径响应低质量食物增加摄食。假设5。通过改变包括钙激活的K+通道sl1在内的一组蛋白质的活性，特定突触的强度可以增加或减少，从而改变行为。这些假设将通过四个具体目标进行测试：目标1：表征食物偏好的行为机制。如果在两种食物中做出选择，蠕虫会选择质量更高的食物。我们将研究身体条件和经验对食物偏好的影响，以了解蠕虫如何评估食物质量，以及蠕虫是否学会识别和选择高质量的食物（假设1-3）。目的2：确定毒蕈碱乙酰胆碱受体影响摄食行为的信号转导途径。正常的蠕虫通过加速进食来补偿低质量的食物。毒蕈碱乙酰胆碱受体是这种反应所必需的。通过研究影响信号系统的药物和突变的作用，我们将确定完整的途径，并确定它如何影响摄食行为（假设4）。目的3：确定SLO-1如何抑制M4->末梢球肌突触。我们将比较野生型和慢-1蠕虫的突触特性，并确定慢-1的哪些特征是抑制突触活动所必需的（假设5）。目标4：确定激活M4->TB神经肌肉连接的突变。我们已经完成了对比正常末端球肌活动更高的突变体的筛选。我们将确定哪些突变激活了M4 NMJ（就像slow -1 null突变一样），并确定它们影响的基因（假设5）。健康相关性：异常的可兴奋细胞功能是许多疾病的根源，从成瘾到神经系统疾病。

DESCRIPTION (provided by applicant): The long-term goal of this research is to understand the genetic basis of animal behavior. The approach is to study the function of the excitable cells that produce feeding behavior, the neurons and muscles of the Caenorhabditis elegans pharynx. In this grant period we will investigate plasticity in feeding behavior. The hypotheses to be tested are: Hypothesis 1. Worms assess the quality of their food. Hypothesis 2. Worms determine whether to seek new food by comparing the quality of their current food with past experience. Hypothesis 3. Worms conditioned on two foods learn to recognize and prefer the higher quality food. Hypothesis 4. Pharyngeal muscarinic acetylcholine receptors activated in response to low quality food increase feeding via a signal transduction pathway that activates MAP kinase MPK-1. Hypothesis 5. By changing the activity of a set of proteins that includes the calcium-activated K+ channel SLO-1, the strength of specific synapses can be increased or decreased, resulting in modified behavior. These hypotheses will be tested through 4 specific aims: Aim 1 : Characterize the behavioral mechanisms of food preference. Given a choice between two foods, worms will select the higher quality one. We will examine the effects of physical conditions and experience on food preference to learn how worms assess food quality and whether worms learn to recognize and choose high-quality food (hypotheses 1-3). Aim 2: Determine the signal transduction pathway by which muscarinic acetylcholine receptors influence feeding behavior. Normal worms compensate for low-quality food by accelerating feeding motions. Muscarinic acetylcholine receptors are necessary for this response. By studying the effects of drugs and mutations that affect signaling systems, we will determine the complete pathway, and determine how it affects feeding behavior (hypothesis 4). Aim 3: Determine how SLO-1 suppresses the M4-> terminal bulb muscle synapse. We will compare the properties of the synapse in wild type and slo-1 worms, and determine what features of SLO-1 are necessary for suppression of synaptic activity (hypothesis 5). Aim 4: Identify mutations that activate the M4->TB neuromuscular junction. We have completed a screen for mutants that have higher than normal terminal bulb muscle activity. We will determine which of these mutations activate the M4 NMJ (as slo-1 null mutations do) and identify the genes they affect (hypothesis 5). Health relevance: Abnormal excitable cell function lies at the root of many diseases, from addiction to neurological disorders.