MECHANISMS OF CENTRAL PATTERN GENERATION IN GANGLIA

这项建议是为了研究中枢神经活动 是由神经肽调节的。我们将使用一个小型模型系统， 龙虾的口胃神经节与CCK和直肠肽 将化学诱导的行为改变与神经元活动联系起来。 CCK在哺乳动物中有荷尔蒙样的作用--作用于大脑以帮助 终止摄食(饱腹感荷尔蒙)，并似乎也诱导一般 大鼠的身体不适。现在有证据表明CCK对这两种疾病都有影响 吗啡和多巴胺受体。它作为一种饱腹感激素的作用 与神经性厌食症等严重进食障碍有关。自.以来 CCK已经定位于CNS神经元，它可能有更多的位置 大脑内的动作，即更多的局部性动作。普罗科托林是一个很小的 五肽，也在哺乳动物的大脑中发现，但它的 到目前为止，行为活动尚不清楚。前列环素与一种CCK样肽 已在口胃系统中发现。口胃网络 是研究多肽作用的理想之选，因为三十个神经元 在这个系统中被识别，并已形成神经回路 描述得很好。尽管已知多肽具有重要的行为 对于它们的实际作用机制，人们知之甚少。 电路和细胞水平。模型系统的使用使我们能够研究 多肽在这个水平上的作用。这个项目将把行为与多肽联系起来 在体内通过同步进行行为量化的行动 运动和中枢神经输出的测量--无论是肌电还是神经记录。 我们将比较自发行为和系统性行为 注射前列环素和CCK。我们将探索内源性的作用 前列环素和一种CCK样肽在胃磨活性产生中的作用 在活体内。这些相同的物质将被应用于体外培养 准备工作。将通过从以下位置删除单元来确定操作地点 该网络使用细胞杀死技术来分离单个神经元和 突触。我们将在体外将调制后的运动模式与 并确定电路中的哪些神经元和突触是 对这些变化负责。

This proposal is to study the mechanisms by which central neural activity is modulated by neuropeptides. We will use a small model system, the stomatogastric ganglion of the lobster and the peptides CCK and proctolin to link chemically induced behavioral modifications with neuronal activity. CCK has hormonal-like actions in mammals -- acting on the brain to help terminate feeding (satiety hormone) and also appears to induce a general malaise in rats. There is evidence now that CCK has effects on both morphine and dopamine receptors. Its action as a satiety hormone has implicated CCK in such severe eating disorders as anorexia nervosa. Since CCK has been localized to CNS neurons it may have additional sites of action within the brain, i.e. more localized actions. Proctolin is a small pentapeptide which has also been found in the mammalian brain but its behavioral activity is as yet unknown. Proctolin and a CCK-like peptide have been found in the stomatogastric system. The stomatogastric networks are ideal for studying the effects of peptides because the thirty neurons in this system are identified and the neural circuits they form have been well described. Although peptides are known to have important behavioral effects, little is known about their actual mechanisms of action at the circuit and cellular level. The use of model systems enables us to study peptide action at this level. This project will link behavior with peptide action by quantifying the behavior in vivo by making simultaneous measurements of movements and CNS output -- either EMG or nerve recordings. We will compare spontaneous behavior with behavior induced by the systemic injection of proctolin and CCK. We will explore the roles of endogenous proctolin and a CCK-like peptide in the generation of gastric mill activity in vivo. These same substances will be bath-applied to the in vitro preparations. The sites of action will be determined by deleting cells from the network using a cell-killing technique to isolate single neurons and synapses. We will compare the modulated motor patterns in vitro to those seen in vivo and determine which neurons and synapses in the circuits are responsible for the changes.