Mechanisms of neuropeptide signaling in the modulation of a serotonergic synapse

5 -羟色胺作为一种神经递质、神经调节剂和激素发挥着重要作用。许多精神疾病的治疗方法，包括重度抑郁症、焦虑症和饮食失调，都以大脑中的血清素信号通路为目标。因此，了解调节血清素信号的分子机制对于理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必不可少的。秀丽隐杆线虫是神经系统功能遗传和分子研究的有力模型。5 -羟色胺能运动神经元和生殖系统肌肉之间的突触驱动秀丽隐杆线虫雌雄同体的生殖行为，即产卵。通过对产蛋行为的遗传研究，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（BAG神经元）提供的，它们受到环境二氧化碳的刺激。本研究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，以及神经肽抑制其靶向的血清素能神经元的机制。

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.