MECHANISMS OF CENTRAL PATTERN GENERATION IN GANGLIA

这项建议是研究中枢神经活动的机制 是由神经肽调节的我们将使用一个小型模型系统， 龙虾的口胃神经节和肽CCK和proctolin 将化学诱导的行为改变与神经元活动联系起来。 CCK在哺乳动物中具有类似于神经元的作用--作用于大脑， 终止喂养（饱腹激素），也似乎诱导一般 老鼠的不适现在有证据表明CCK对两者都有影响 吗啡和多巴胺受体。它作为一种饱腹激素的作用， CCK与神经性厌食症等严重饮食失调有关。以来 CCK已定位于CNS神经元，它可能具有额外的位点， 大脑内部的活动，即更局部化的活动。Proctolin是一种小型 五肽，也已发现在哺乳动物的大脑，但其 行为活动尚不清楚。Proctolin和CCK样肽 在胃肠道系统中发现。口胃网络 是研究缩氨酸效应的理想选择，因为这30个神经元 在这个系统中，它们被识别出来，它们形成的神经回路被 描述得很好。尽管已知肽具有重要的行为学功能， 影响，很少有人知道他们的实际作用机制， 电路和细胞水平。模型系统的使用使我们能够研究 在这个水平上的肽作用。这个项目将把行为与肽联系起来 通过同时进行体内行为的量化， 运动和中枢神经系统输出的测量--肌电图或神经记录。 我们将比较自发行为和系统性行为引起的行为。 注射丙诺啡和CCK。我们将探讨内源性 肠溶肽和CCK样肽在胃磨活性产生中的作用 in vivo.这些相同的物质将被应用于体外 准备工作作用部位将通过删除细胞来确定， 该网络使用细胞杀伤技术来分离单个神经元， 突触我们将比较体外调制的运动模式与那些 在体内观察，并确定回路中的哪些神经元和突触 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.