Development of a lifespan monkey model of interoception

项目摘要 几十年的相关研究表明，一个人整合生理信息的能力 并感受或体验这些生理信号，这一过程被称为内感受， 健康和恶化的整个生命周期，即使在健康的老龄化。了解这些机制， 因此，介导的内感受过程对于开发广泛的治疗和干预措施至关重要。 与内感受器相关的疾病和衰老相关的过程。这种机械研究需要 有能力因果操纵潜在的神经生物学和环境基质的内感受， 这就需要动物模型。在拟议的工作中，我们开发了一个高度可翻译的动物模型， 用行为任务评价恒河猴心脏内感受能力 （Macaca mulatta），然后通过开发一项行为任务， 引导情感相关认知的内感受信号。我们还研究了心脏的个体差异 功能与内感受能力的变化有关，以建立猴子之间的功能同源性， 人类这项创新性的工作将是第一个使用可翻译的测量心脏内感受能力 并为进一步的机械研究奠定了基础，以了解如何以及为什么 内感受在整个生命周期中以及在从情绪障碍到 神经退行性疾病如阿尔茨海默氏症最终，了解生物学机制， 内感受对于开发内感受相关疾病的治疗和干预是必要的， 促进整个生命周期的健康。

Project Summary Decades of correlational research have revealed that a person’s ability to integrate physiological information from the body and sense or experience those physiological signals, a process known as interoception, is critical to health and deteriorates across the lifespan, even in healthy aging. Understanding the mechanisms that mediate interoceptive processes is therefore critical for developing treatments and interventions for a broad array of interoception-related diseases and aging-related processes. Such mechanistic investigations require the capacity to causally manipulate potential neurobiological and environmental substrates of interoception, which necessarily requires an animal model. In the proposed work, we develop a highly translatable animal model of interoception by developing a behavioral task to evaluate cardiac interoceptive ability in rhesus monkeys (Macaca mulatta) and then by developing a behavioral task that indexes the extent to which monkeys use cardiac interoceptive signals to guide affect-related cognition. We also examine how individual variation in cardiac function relates to variation in interoceptive ability to establish functional homologies between monkeys and humans. This innovative work will be the first to use a translatable measurement of cardiac interoceptive ability in nonhuman animals and sets the stage for further mechanistic investigations to understand how and why interoception changes across the lifespan and in a variety of diseases ranging from mood disorders to neurodegenerative disorders like Alzheimer’s disease. Ultimately, understanding the biological mechanisms of interoception is necessary to develop treatments and interventions for interoception-related diseases and to promote wellbeing across the lifespan.