Coordinated regulation of feeding and social preferences by oxytocin in the rat and human

催产素对大鼠和人类进食和社会偏好的协调调节

• 批准号: 447311929
• 负责人: Professor Dr. Valery Grinevich
• 金额: --
• 依托单位: Sagol Department of Neurobiology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/447311929?language=en
• 关键词: Coordinated; regulation; feeding; social; preferences

The hypothalamic neuropeptide oxytocin (OT) is a crucial actor in the regulation of both social communication and feeding. However, it is largely unknown how one molecule – OT – can discriminately coordinate such distinct forms of behaviors. Based on accumulated reports that the insular cortex (IC) serves as the hub controlling both feeding and social behaviors, in our project we aim to investigate how OT signaling in the IC may form a preference towards food vs. conspecifics. To achieve this aim, we have built an international team in the framework of the DFG-Middle East program by experts in the functional anatomy of the OT system (Valery Grinevich, Mannheim), social behavior and in vivo electrophysiology (Shlomo Wagner, Haifa), and cellular/molecular biology of the IC (Kobi Rosenblum, Haifa). Using recently generated OT receptor (OTR) knock-in rats, we will implement an interdisciplinary approach to dissect (i) specific OTR circuits within the IC, (ii) investigate how OT modulates local networks in the IC, and (iii) study how evoked endogenous OT release within the IC contributes to goal-directed behavior, e.g., making a choice between two rewarding stimuli – food vs. conspecifics. In parallel, we will study the activity of the OT system and OTR neurons in the IC, using fiber photometry and extracellular recording in awake behaving rats, respectively. Next, applying cutting edge cellular and molecular techniques, including newly developed activity-dependent tagging of activated cells (termed CRAM), we will dissect intracellular pathways downstream of OTR, which are activate within IC neurons when the animal encounters innate or learned appetitive or aversive food sources or social experiences. Finally, we will study OTR expression and OTR intracellular signaling in cortical neurons differentiated from pluripotent stem cells from healthy adult male humans. Thus, in addition to gaining a novel information on functional diversity within the OT system, distinctly or concomitantly modulating social and feeding behaviors, our results will be highly translatable to human pathologies, such as Prader-Willi syndrome, characterized by joint alterations in social competence, feeding, and OT synthesis.

下丘脑神经肽催产素（OT）是调节社会交往和进食的关键因素。然而，很大程度上还不知道一个分子- OT -如何能够有区别地协调这种不同形式的行为。基于岛叶皮层（IC）作为控制进食和社会行为的枢纽的累积报告，在我们的项目中，我们的目标是研究IC中的OT信号如何形成对食物与同种动物的偏好。为了实现这一目标，我们在DFG-中东计划的框架内建立了一个国际团队，由OT系统功能解剖学（Valery Grinevich，曼海姆），社会行为和体内电生理学（Shlomo瓦格纳，海法）以及IC细胞/分子生物学（Kobi Rosenblum，海法）的专家组成。使用最近产生的OT受体（OTR）敲入大鼠，我们将实施跨学科的方法来解剖（i）IC内的特定OTR回路，（ii）研究OT如何调节IC中的局部网络，以及（iii）研究IC内诱发的内源性OT释放如何有助于目标导向行为，例如，在两种奖励刺激物之间做出选择-食物与同种物。与此同时，我们将研究OT系统和OTR神经元在IC的活动，在清醒行为的大鼠，分别使用纤维光度法和细胞外记录。接下来，应用尖端的细胞和分子技术，包括新开发的激活细胞的活动依赖性标签（称为CRAM），我们将剖析OTR下游的细胞内途径，当动物遇到先天或习得的食欲或厌恶时，这些途径会在IC神经元内激活。食物来源或社交经历。最后，我们将研究从健康成年男性多能干细胞分化的皮质神经元中OTR表达和OTR细胞内信号传导。因此，除了获得关于OT系统内功能多样性的新信息，明显或伴随地调节社会和进食行为外，我们的结果将高度可转化为人类病理学，例如Prader-Willi综合征，其特征在于社会能力，进食和OT合成的联合改变。