NEUROBIOLOGY OF IDENTIFIED PEPTIDERGIC NEURONS

该项目的长期目标是在手机上了解 调整控制相互作用的机制 肽能神经元和其他细胞。神经肽具有深刻的 对包括神经系统在内的多种身体组织的影响 从低等无脊椎动物到人类。他们表演的是 从神经递质到各种生理作用 神经荷尔蒙。飞蛾Manduca的神经系统 Sexta提供了一个特别吸引人的模型系统，其中 电生理、内分泌、生化和 发育实验可以在体内方便地进行 以及在体外单独识别的肽能神经元上。这个 因此，神经肽的细胞作用可以遵循 这个无脊椎动物系统的精确度比目前的任何系统都要高 脊椎动物制剂，神经肽的细胞学研究 已经被证明是困难的。 这项研究的主要焦点将是6个单独确定的 该蛾体内的肽能神经元含有两个新的 神经肽。我们之前已经证明了这两个肽， 被称为心脏加速肽(CAP)，发挥着重要的作用 成体涌现行为中的心脏调节作用 飞蛾。这项提案将利用多学科方法来 CAP的电生理和生化检查 功能。 人们对其电生理机制知之甚少 调节含肽神经元的活动。细胞内 活动的CAP神经元的录音将在成年期间获得 涌现行为。在这些实验中，大脑中的电活动 单个CAP神经元的数量将直接与 释放了多肽。其他实验，在这些实验中神经元 CAP神经元的输入被识别，将提供关键的新的 关于肽能神经元的神经控制信息和 多肽释放。 上限对其目标的行动模式也将是 探索过了。这些帽子的电生理效应将是 对单独分离的心肌纤维的研究 常规和电压钳位记录。生物化学基础 CAP对心脏的作用也将通过测量 环磷酰胺诱导的细胞内循环水平的变化 核苷酸和/或肌醇磷酸盐。

The long-term goal of this project is to understand at the cellular level the mechanisms which control the interactions between peptidergic neurons and other cells. Neuropeptides have profound effects on many body tissues including the nervous system of most animals from lower invertebrates to humans. They perform a wide variety of physiological roles ranging from neurotransmitter to neurohormone. The nervous system of the moth, Manduca sexta, provides a particularly attractive model system in which electrophysiological, endocrinological, biochemical and developmental experiments can be performed conveniently in vivo and in vitro on individually identifiable peptidergic neurons. The cellular action of neuropeptides can therefore be followed with greater precision in this invertebrate system than in any present vertebrate preparation, where cellular studies on neuropeptides have proven difficult. The primary focus of this study will be 6 individually identified peptidergic neurons in the moth which contain two novel neuropeptides. We have previously shown that these two peptides, known as cardioacceleratory peptides (CAPs), play important cardioregulatory roles during adult emergence behavior in the moth. This proposal will utilize a multidisciplinary approach to examine electrophysiological and biochemical aspects of CAP function. Little is known about the electrophysiological mechanisms that regulate the activity of peptide-containing neurons. Intracellular recordings from active CAP neurons will be obtained during adult emergence behavior. In these experiments, electrical activity in individual CAP neurons will be directly related to the amount of peptide released. Additional experiments, in which the neuronal inputs to the CAP neurons are identified, will provide crucial new information on the neural control of peptidergic neurons and peptide release. The mode of action of the CAPs on their targets will also be explored. The electrophysiological effects of the CAPs will be studied in individually dissociated heart muscle fibers using conventional and voltage clamp recordings. The biochemical basis of CAP action on the heart will also be investigated by measuring CAP induced changes in the intracellular levels of cyclic nucleotides and/or inositol phosphates.