Oxytocin Modulation of Social Behavior

催产素对社会行为的调节

• 批准号: 10402125
• 负责人: Ismail A. Ahmed
• 金额: $ 5.4万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10402125
• 关键词: Behavior; Brain; Caring; Clinic; Cues; Detection; Development; Diagnostic; Electrophysiology (science); Fiber; Goals; Life; Link; Measurement; Measures; Mus; Neurons; Neuropeptides; Optics; Oxytocin; Pattern; Phase; Photometry; Physiological; Postpartum Depression; Regulation; Reproduction; Role; Signal Transduction; Social Behavior; Social Behavior Disorders; Social Environment; Social Interaction; Testing; Time; behavioral phenotyping; behavioral study; child neglect; experimental study; in vivo; innovation; insight; nanosensors; neural circuit; neural network; social; social cognition; tool

The goal of this proposal is to dissect the underlying mechanisms and relationships of oxytocin release in the mouse brain as involved in various social behaviors. Oxytocin is an evolutionarily conserved neuropeptide associated with various social behaviors essential for life, such as social interaction, parental care, reproduction, defense, and more. An emerging view in the field is that disruptions in oxytocin signaling may be involved in disorders of social behavior, social cognition, and parental care (including child neglect or postpartum depression). However, it is unclear how, when, or where oxytocin is released in the brain to enact on specific neural circuits to enable social behavior. Therefore. It is essential to delineate the physiological role of oxytocin in the context of social behavior. The overall hypothesis is that oxytocin is rarely released, but episodes of phasic release predict sudden changes in social behavior, in a manner consistent with enhancing the salience of social (audible) cues. To test this fundamental question, I will first carry out (Aim 1) behavioral studies to identify the most robust social behavior phenotypes in mice that are sensitive to oxytocin regulation (activation and suppression). Then (Aim 2) I will develop and validate a synthetic nanosensor for real-time optical tracking of oxytocin in vivo. Lastly, (Aim 3) I will use the oxytocin nanosensor to follow in real-time oxytocin release and distribution during the behaviors identified in Aim 1, as well as employ fiber photometry and electrophysiology to measure the cortical and oxytocin neuron firing patterns associated with these behaviors. Innovation: The development of the oxytocin nanosensor will be a highly useful tool likely to be used by many as well as can serve as a basis for diagnostic measurement if oxytocin in the clinic. Taken together, the experiments to be performed in this proposal will provide valuable insight on the release and action of oxytocin in the brain and the related neural networks during social behavior.

该提案的目标是剖析催产素的潜在机制和关系 小鼠大脑中参与各种社会行为的释放。催产素是一种进化的 与生命必需的各种社会行为相关的保守神经肽，例如 社交互动、父母照顾、繁殖、防御等等。该领域的新兴观点 催产素信号传导的破坏可能与社会行为、社交障碍有关 认知和父母照顾（包括儿童忽视或产后抑郁症）。然而，它是 尚不清楚催产素如何、何时或何地在大脑中释放并作用于特定的神经回路 以实现社交行为。所以。描述催产素的生理作用至关重要 在社会行为的背景下。总体假设是催产素很少释放，但是 阶段性释放的发作以一致的方式预测社会行为的突然变化 增强社交（声音）线索的显着性。为了测试这个基本问题，我首先 进行（目标 1）行为研究，以确定最稳健的社会行为表型 对催产素调节（激活和抑制）敏感的小鼠。然后（目标 2）我会 开发并验证一种合成纳米传感器，用于体内催产素的实时光学跟踪。 最后，（目标 3）我将使用催产素纳米传感器来跟踪实时催产素释放和 目标 1 中确定的行为期间的分布，以及采用光纤光度测定法和 电生理学测量与相关的皮质和催产素神经元放电模式 这些行为。创新：催产素纳米传感器的开发将是一个非常有用的 许多人可能会使用该工具，并且可以作为诊断测量的基础，如果 催产素在诊所。总而言之，本提案中要进行的实验将 提供有关大脑中催产素的释放和作用以及相关神经的宝贵见解 社交行为过程中的网络。