Contributions of hippocampal oxytocin receptors to social recognition

项目摘要 哺乳动物的社会认知是一个复杂的生物过程，需要 神经回路调节认知过程，如对社会刺激和潜在刺激的辨别 表达从属关系或回避行为。损害社会歧视、社会歧视的巡回修改 社会歧视与社会互动的相互作用或联系可能是社会认可度缺失的基础 可见于自闭症谱系障碍和其他精神障碍。一种通用的机制，通过它不同的 诸如寻求奖励、社会探索和社会刺激歧视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已经 开始阐明伏核、外侧隔核和下丘脑中的催产素受体(OXTR)信号 在社会互动中，海马区Oxtrs对社会记忆的贡献 为人所知。这项建议试图确定(I)海马OXTR 信号传递促进对社会刺激的辨别，以及(Ii)连接这些计算的神经通路 有辅助社交互动的电路。为了实现这些目标，我们将利用病毒和老鼠条件 遗传工具、光遗传学、细胞集合成像和行为精确操纵海马区OXTR 以前所未有的空间和时间控制发送信号，并确定其对社会的贡献 承认。从拟议的研究中收集的见解将有助于阐明一种古老的神经调节剂是如何 OT已经发展到利用基本的记忆处理电路机制来执行社会辨别 刺激物。这些研究的意义在于它有可能阐明基本的神经机制。 之前未被认识到的海马区OXTR信号在社会识别中的作用。最终， 这些机制可能会指导新的治疗策略，以促进精神障碍的社会认可 而这一点却受到了损害。

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.