Brain control of internal organ function

大脑控制内脏器官功能

• 批准号: 10261685
• 负责人: Rui M. Costa
• 金额: $ 113.4万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261685
• 关键词: Adaptive Behaviors; Anatomy; Animals; Anxiety; Apple; Area; Award; Behavior Control; Behavioral; Brain; Chest; Food; Genetic; Health; Homeostasis; Immunosuppression; Insulin; Learning; Maps; Measures; Mediating; Mental Depression; Mental disorders; Mesentery; Methods; Motor; Motor Cortex; Movement; Muscle; Nervous system structure; Neurologic; Neurons; Optics; Organ; Organism; Pancreas; Physiological; Physiology; Population; Positioning Attribute; Research; Resolution; Sensory; Spinal Cord; Spleen; Stroke; Sympathetic Ganglia; Testing; Viral; arm; conditioning; expectation; in vivo calcium imaging; innovation; internal control; mind control; motor control; nerve supply; neural circuit; novel; optogenetics; relating to nervous system; response; tool; transcriptome sequencing; viral RNA

Abstract Adaptive control of behavior is critical for survival. Even a simple movement, like extending the arm, requires the activation of many neuronal populations across the nervous system. Our lab has used a combination of anatomical, genetic, optical and behavioral approaches to unravel how animals move, and learn to control movement. However, adaptive responses are not effected only through muscles, but also through other organs. For example, planning to pick an apple will trigger not only muscle activity but also the expectation of food, and the conditioned release of insulin. Hence adaptive behavior requires the coordination of an organism's actions with its physiological internal states. We propose to leverage our expertise to dissect the neural circuits and principles governing the learning and adaptive “motor” control of internal organ function. We will spearhead this new research direction by investigating conditioned insulin release and conditioned immunosuppression, mediated by the innervation of the pancreas and spleen, respectively. We will leverage state of the art viral and RNA-seq approaches to map with high-resolution the first, second and third-order innervation of spleen and pancreas. Our preliminary anatomical mapping of the innervation of these organs revealed that different populations of celiac-mesenteric ganglia sympathetic neurons innervate pancreas versus spleen. Remarkably, most innervation of the thoracic preganglionic spinal cord targeting these organs emerges from the cortex: motor cortex, but also sensory and prefrontal. We therefore hypothesize that learning to select the appropriate responses in internal organs after conditioning is mediated by higher-order brain circuits, and follows principles similar to those used for motor responses. We propose to use both targeted and unbiased approaches to identify and manipulate the activity of descending neural populations responsible for the learned control of spleen and pancreatic function. This new line of research is innovative but trackable with our expertise, and the Pioneer award support will help us attack this novel research area. Importantly, the proposed research has the potential to conceptually position the nervous system as a “smart” regulator of organism homeostasis, and hence impact health in unexpected ways - mental disorders like anxiety and depression, or neurological problems like stroke, are associated with abnormal physiological states likely emerging from these brain-internal organ interactions.

摘要 行为的适应性控制对生存至关重要。即使是一个简单的动作，比如伸展手臂， 整个神经系统中许多神经元群体的激活。我们的实验室使用了 解剖学、遗传学、光学和行为学方法来解开动物如何移动，并学会控制 运动然而，适应性反应不仅通过肌肉，而且还通过其他 机关例如，计划摘一个苹果不仅会触发肌肉活动，还会触发预期 以及胰岛素的条件释放。因此，适应性行为需要协调 生物体的行为与其生理内部状态。我们建议利用我们的专业知识来剖析 神经回路和原则的学习和适应性“运动”控制内部器官的功能。 我们将通过研究条件性胰岛素释放和条件性胰岛素释放， 免疫抑制，分别由胰腺和脾脏的神经支配介导。我们将利用 最先进的病毒和RNA-seq方法，以高分辨率绘制第一，第二和第三级 脾和胰腺的神经支配。我们对这些器官神经支配的初步解剖图 揭示了不同群体的腹腔-肠系膜神经节交感神经元支配胰腺 对比脾脏值得注意的是，胸节前脊髓的大多数神经支配针对这些器官， 从大脑皮层发出：运动皮层，还有感觉皮层和前额叶皮层。因此，我们假设， 学习选择适当的反应后，内部器官的条件是介导的高阶 大脑回路，并遵循类似于用于运动反应的原理。我们建议两者都使用 有针对性和公正的方法来识别和操纵下行神经群体的活动 负责脾和胰腺功能的学习控制。这一新的研究方向是创新的 但我们的专业知识可以跟踪，先锋奖的支持将帮助我们攻击这个新的研究领域。 重要的是，这项拟议中的研究有可能在概念上将神经系统定位为“智能”系统。 生物体内平衡的调节器，因此以意想不到的方式影响健康-精神障碍， 焦虑和抑郁，或神经问题，如中风，与异常的生理 这些状态很可能是由大脑和内部器官的相互作用产生的。