NEUROBIOLOGY OF IDENTIFIED PEPTIDERGIC NEURONS

这个项目的长期目标是了解在细胞 平衡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 影响许多身体组织，包括大多数人的神经系统 从低等无脊椎动物到人类。 它们执行 各种各样的生理作用，从神经递质 神经激素 天蛾的神经系统 Sexta提供了一个特别有吸引力的模型系统，其中 电生理学、内分泌学、生物化学和 可以方便地在体内进行发育实验， 以及在体外对单独可识别的肽能神经元的作用。 的 因此，神经肽的细胞作用可以通过以下方式进行： 这种无脊椎动物系统的精确度比目前任何 脊椎动物制备，其中对神经肽的细胞研究 已经证明是困难的 本研究的主要重点将是6个单独确定的 肽能神经元在蛾，其中含有两个新的 神经肽 我们之前已经证明了这两种肽， 称为心脏加速肽（CAPs）， 在成年人出现行为过程中的心脏调节作用 蛾 该提案将采用多学科方法， 检查CAP的电生理和生物化学方面 功能 人们对电生理机制知之甚少， 调节含肽神经元的活性。 细胞内 将在成年期间获得来自活跃CAP神经元的记录。 涌现行为 在这些实验中， 单个CAP神经元将直接与 肽释放 另外的实验，其中神经元 CAP神经元的输入被识别，将提供关键的新的 肽能神经元的神经控制信息， 肽释放 联合呼吁程序对其目标的作用方式也将是 探讨了 CAP的电生理效应将是 在单独分离的心肌纤维中研究， 常规和电压钳记录。 生物化学基础 CAP对心脏的作用也将通过测量 CAP诱导的细胞内循环水平的变化， 核苷酸和/或肌醇磷酸。

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.