Genetics of nematode pharyngeal muscle excitability

线虫咽肌兴奋性的遗传学

• 批准号: 6728898
• 负责人: Leon Avery
• 金额: $ 27.02万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-05 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6728898
• 关键词: Caenorhabditis elegans; action potentials; biological signal transduction; gene expression; gene mutation; mitogen activated protein kinase; muscarinic receptor; muscle cells; neuromuscular junction; neurons; oral pharyngeal; potassium channel; synapses

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.

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。该方法是研究产生摄食行为的可兴奋细胞，即秀丽隐杆线虫咽部神经元和肌肉的功能。在这段时间里，我们将研究摄食行为的可塑性。待检验的假设是：假设1。蠕虫评估食物的质量。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.以两种食物为条件的蠕虫学会识别和喜欢高质量的食物。假设4.咽部毒蕈碱型乙酰胆碱受体在低质量食物下被激活，通过激活MAP激酶MPK-1的信号转导途径增加摄食。假设5.通过改变包括钙激活的K+通道SLO-1在内的一组蛋白质的活性，可以增加或减少特定突触的强度，从而改变行为。这些假设将通过4个具体目标进行测试：目标1：描述食物偏好的行为机制。如果有两种食物可供选择，蠕虫会选择质量较高的那一种。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：确定毒蕈碱型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动作来补偿低质量的食物。毒蕈碱型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影响，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->末端球肌突触。我们将比较野生型和SLO-1蠕虫中突触的性质，并确定SLO-1的哪些特征是抑制突触活动所必需的（假设5）。目的4：识别激活M4->TB神经肌肉接头的突变。我们已经完成了一个筛选突变体，具有高于正常的终端球肌肉活动。我们将确定这些突变中的哪一个激活了M4 NMJ（就像M4 -1无效突变一样），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。