Contributions of hippocampal oxytocin receptors to social recognition

海马催产素受体对社会认可的贡献

基本信息

批准号：
10056173
负责人：
Amar Sahay
金额：
$ 42.25万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-11-15 至 2022-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10056173
关键词：
Address Adult Anxiety Attenuated Behavior Behavioral Biological Process Cells Cellular Compartment Analysis Code Communication Complex Data Disease Dorsal Excision Exposure to Feedback Female Fluorescent in Situ Hybridization Genetic Glean Goals Hilar Hippocampus (Brain)Image Impairment Lateral Light Link Mammals Mediating Memory Mental disorders Mus Neural Pathways Neuromodulator Neurons Noise Nucleus Accumbens Oxytocin Oxytocin Receptor Pathway interactions Pattern Pharmacology Prefrontal Cortex Process Prosencephalon Receptor Signaling Rewards Role Signal Transduction Social Behavior Social Discrimination Social Interaction Stimulus Testing Viral attenuation autism spectrum disorder avoidance behavior base cognitive process conditional mutant dentate gyrus design hippocampal pyramidal neuron insight male memory process neural circuit neuromechanism novel novel therapeutic intervention object recognition optogenetics population based receptor expression social social separation tool

项目摘要

Project Summary Social recognition in mammals is a complex biological process that necessitates communication between neural circuits mediating cognitive processes such as discrimination of social stimuli and those underlying expression of affiliation or avoidance behaviors. Circuit alterations that impair social discrimination, social interaction or linkage of social discrimination with social interaction may underlie social recognition deficits seen in autism spectrum disorders and other psychiatric disorders. One general mechanism by which distinct behaviors such as reward seeking, social exploration and discrimination of social stimuli are orchestrated is through the actions of neuromodulators such as oxytocin (OT). Although a growing number of studies have begun to shed light on oxytocin receptor (Oxtr) signaling in the nucleus accumbens, lateral septum and prefrontal cortex in social interaction, the contribution of Oxtrs in the hippocampus to social memory is not known. This proposal seeks to identify (i) fundamental circuit mechanisms by which hippocampal Oxtr signaling promotes discrimination of social stimuli and, (ii) the neural pathways that link these computations with circuits that subserve social interaction. Towards these goals, we will harness viral and mouse conditional genetic tools, optogenetics, cellular ensemble imaging and behavior to precisely manipulate hippocampal Oxtr signaling with unprecedented spatial and temporal control and determine its contributions to social recognition. Insights gleaned from the proposed studies will shed light on how an ancient neuromodulator like OT has evolved to utilize basic memory-processing circuit mechanisms to perform discrimination of social stimuli. The significance of the studies lies in its potential to illuminate fundamental neural mechanisms underlying previously unrecognized roles of hippocampal Oxtr signaling in social recognition. Ultimately, these mechanisms may guide novel therapeutic strategies for promoting social recognition in disorders in which it is impaired.

项目概要哺乳动物的社会识别是一个复杂的生物过程，需要动物之间的交流介导认知过程的神经回路，例如社会刺激及其潜在刺激的辨别表达归属或回避行为。损害社会歧视、社会歧视的电路改变社会歧视与社会交往的相互作用或联系可能是社会认可缺陷的基础见于自闭症谱系障碍和其他精神疾病。一种通用机制，通过该机制可以区分寻求奖励、社会探索和社会刺激辨别等行为是精心策划的通过催产素 (OT) 等神经调节剂的作用。尽管越来越多的研究表明开始揭示伏隔核、侧隔和中隔核中的催产素受体（Oxtr）信号传导前额皮质在社交互动中，海马中的 Oxtrs 对社交记忆的贡献并不大已知。该提案旨在确定 (i) 海马 Oxtr 的基本回路机制信号传导促进了对社会刺激的辨别，以及（ii）连接这些计算的神经通路具有促进社交互动的电路。为了实现这些目标，我们将利用病毒和小鼠条件遗传工具、光遗传学、细胞整体成像和行为来精确操纵海马 Oxtr 具有前所未有的空间和时间控制的信号传递，并确定其对社会的贡献认出。从拟议的研究中收集的见解将揭示古代神经调节剂如何 OT 已经发展到利用基本的记忆处理电路机制来执行社会歧视刺激。这些研究的意义在于它有可能阐明基本的神经机制海马 Oxtr 信号在社会识别中的作用是以前未被认识到的。最终，这些机制可能会指导新的治疗策略，以促进疾病的社会认可它受到损害。