Mechanisms of neuropeptide signaling in the modulation of a serotonergic synapse

描述(申请人提供)：描述5-羟色胺作为神经递质、神经调节剂和激素发挥重要作用。治疗许多精神疾病，包括严重的抑郁症、焦虑症和进食障碍，靶向大脑中的5-羟色胺信号通路。因此，了解调节5-羟色胺信号的分子机制对于了解许多类型的神经和精神疾病的原因以及开发新的治疗方法都是至关重要的。线虫是研究神经系统功能的遗传学和分子生物学的有力模型。5-羟色胺能运动神经元和生殖系统肌肉之间的突触驱动线虫两性的生殖行为，即产卵。通过对产卵行为的遗传学研究，我们发现神经肽通过直接抑制5-羟色胺能运动神经元来调节线虫生殖系统中的5-羟色胺信号。其中一些调节性神经肽是由一对感觉神经元提供的，袋状神经元受到环境二氧化碳的刺激。这项建议的目的是确定二氧化碳激活多肽能感觉神经元所需的生理和分子机制，以及神经肽抑制它们所针对的5-羟色胺能神经元的机制。

DESCRIPTION (provided by applicant): description Serotonin plays critical roles as a neurotransmitter, neuromodulator and hormone. Therapeutics for many psychiatric disorders, including major depression, anxiety disorders and eating disorders, target serotonin signaling pathways in the brain. Understanding molecular mechanisms that regulate serotonin signaling is therefore essential both for understanding the causes of many types of neurological and psychiatric illness and for developing new therapeutics. The roundworm C. elegans is a powerful model for genetic and molecular studies of nervous system function. A synapse between serotonergic motor neurons and muscles of the reproductive system drives the reproductive behavior of the C. elegans hermaphrodite, egg laying. Through genetic studies of egg-laying behavior, we have discovered that neuropeptides modulate serotonin signaling in the C. elegans reproductive system by directly inhibiting serotonergic motor neurons. Some of these modulatory neuropeptides are provided by a pair of sensory neurons, the BAG neurons, which are stimulated by environmental carbon dioxide. The aim of this proposal is to determine physiological and molecular mechanisms required for the activation of peptidergic sensory neurons by carbon dioxide, and mechanisms by which neuropeptides inhibit the serotonergic neurons that they target.