RUI: Serotonergic Control of Feeding

RUI：进食的血清素控制

• 批准号: 9514483
• 负责人: Bruce O'Gara
• 金额: $ 12万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9514483&HistoricalAwards=false
• 关键词: RUI; Serotonergic; Control; Feeding

9514483 O'Gara The experiments described in this proposal will examine how the nervous system controls the feeding behavior of the medicinal leech. The physiological mechanisms used by the leech nervous system to control behavior are similar to those found in higher animals, including humans. The relative simplicity of the leech nervous system allows us to examine some of these physiological mechanisms in ways that are difficult or impossible in higher animals. An additional justification for studying feeding in the leech is the re- emergence of the use of leeches following plastic and reconstructive surgery. When an amputated part of the body (like a finger or an ear) is reattached, it is relatively easy for the surgeon to reattach the arteries in the affected body part. However, veins are more delicate and blood is more likely to clot in them. Because of these problems, blood within the reattached body part has no way to return to the rest of the body. Pressure builds up in the reattached part and blood flow stops. Without treatment, the tissue will die. When these problems occur, the surgeon can restore blood flow to the affected tissue using leeches. The leech will feed on the congested tissue and drain it of blood. In addition, the bite mark left by the leech will ooze blood for a number of hours. These two actions will allow new blood to flow into the reattached tissue and keep it alive. Efforts to mimic these actions artificially have been unsuccessful; thus, there is no substitute for the use of leeches in these situations. A better understanding of how leech feeding is controlled may allow doctors to more efficiently utilize leeches in this role. Nerve cells (called neurons) communicate with other neurons and muscle cells by releasing a chemical called a neurotransmitter. The neurotransmitter changes the behavior of the recipient neuron or causes a change in tension of a muscle cell. The neurotransmitter is sens ed by the recipient cell using protein molecules called receptors. Receptors for a particular neurotransmitter usually come in a number of varieties. The different receptors can be preferentially activated using specific drugs that resemble the neurotransmitter. Feeding behavior of the leech is dependent on the neurotransmitter serotonin. The experiments in this proposal will examine the effects of serotonin on the nervous system and muscle cells of the gut. In the first series of experiments, we will examine the effects of serotonin (and similar acting drugs) on biting behavior and blood consumption. By the use of specific drugs that activate only certain types of serotonin receptors, we will examine the role of the various receptors in feeding. We will also record the electrical activity of the muscles involved in feeding using very fine wires implanted in these muscles. These experiments will allow us to examine how serotonin turns on feeding behavior. In a second set of experiments we will examine the effects of serotonin-like drugs on the contractions of the leech pharynx after we have removed it from the body. The pharynx is the first part of the gut and actually generates the suction that draws blood from the victim. These experiments are designed to allow us to deduce what types of serotonin receptors are present on the muscles of the pharynx, and the role of each receptor type in controlling contractions of the pharynx. The last series of experiments will examine the effects of serotonin-like drugs on individual pharyngeal muscle cells. Using fine microelectrodes that are inserted into individual cells, we will examine the effects of these drugs on the muscle cell membrane. We will examine the effects of serotonin-like drugs on the permeability of the cell membrane to ions (charged atoms). The movement of ions across the cell membrane triggers the events that eventually lead to muscle contraction. These studies will a llow us to examine the role of various serotonin receptors in regulating muscle contraction at the level of the individual cell.

9514483奥加拉这项提案中描述的实验将研究神经系统如何控制药用水蚤的取食行为。水蚤神经系统用来控制行为的生理机制与包括人类在内的高等动物的生理机制相似。水蚤神经系统的相对简单使我们能够以在高等动物中很难或不可能的方式来检查其中一些生理机制。研究在水蚤中进食的另一个理由是，在整形和重建手术后，再次出现了使用水蚤的现象。当身体的截肢部分(如手指或耳朵)重新连接时，外科医生相对容易地重新连接受影响身体部分的动脉。然而，静脉更脆弱，血液更容易凝结在里面。由于这些问题，重新连接的身体部位内的血液无法返回到身体的其他部位。压力在重新连接的部分积聚，血液流动停止。如果不治疗，组织就会死亡。当这些问题发生时，外科医生可以使用水蛭恢复受影响组织的血液流动。水蚤将以充血的组织为食，并将其排出血液。此外，水蚤留下的咬痕会渗血数小时。这两个行动将允许新的血液流入重新连接的组织并使其存活。人为地模仿这些动作的努力一直没有成功；因此，在这些情况下，没有什么可以替代水蚤的使用。更好地了解水蚤喂食是如何控制的，可能会让医生更有效地利用水蚤来发挥这一作用。神经细胞(称为神经元)通过释放一种名为神经递质的化学物质与其他神经元和肌肉细胞进行交流。神经递质改变受体神经元的行为或引起肌肉细胞张力的变化。神经递质是由受体细胞使用称为受体的蛋白质分子来感应的。一种特定神经递质的受体通常有很多种。不同的受体可以优先使用类似神经递质的特定药物来激活。水蚤的取食行为依赖于神经递质5-羟色胺。这项提案中的实验将检验5-羟色胺对神经系统和肠道肌肉细胞的影响。在第一系列实验中，我们将研究5-羟色胺(和类似的作用药物)对咬人行为和血液消耗的影响。通过使用仅激活某些类型的5-羟色胺受体的特定药物，我们将检查各种受体在摄食中的作用。我们还将使用植入这些肌肉中的非常细的电线来记录参与进食的肌肉的电活动。这些实验将使我们能够检查5-羟色胺如何影响进食行为。在第二组实验中，我们将检查5-羟色胺类药物在从体内移除水蛭咽部后对其收缩的影响。咽部是肠道的第一部分，实际上会产生吸血作用，吸出受害者的血液。这些实验旨在让我们推断咽部肌肉上存在哪些类型的5-羟色胺受体，以及每种受体类型在控制咽部收缩中的作用。最后一系列实验将检验5-羟色胺类药物对个别咽部肌肉细胞的影响。使用插入单个细胞的精细微电极，我们将检查这些药物对肌肉细胞膜的影响。我们将研究5-羟色胺类药物对细胞膜对离子(带电原子)的通透性的影响。离子在细胞膜上的移动会触发最终导致肌肉收缩的事件。这些研究将使我们能够研究不同的5-羟色胺受体在个体细胞水平上调节肌肉收缩的作用。