Brain control of internal organ function

大脑控制内脏器官功能

• 批准号: 10703497
• 负责人: Rui M. Costa
• 金额: $ 114.83万
• 依托单位: ALLEN INSTITUTE
• 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 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703497
• 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; 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; neural circuit; novel; optogenetics; response; tool; transcriptome sequencing

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 对行为的适应性控制是生存的关键。即使是一个简单的动作，如伸展手臂，也需要 神经系统中许多神经元群的激活。我们的实验室使用了一种 用解剖学、遗传学、光学和行为学的方法来解开动物的运动方式，并学会控制 有动静。然而，适应性反应不仅通过肌肉，还通过其他 器官。例如，计划摘一个苹果不仅会引发肌肉活动，还会引发预期 以及胰岛素的条件性释放。因此，自适应行为需要协调 生物体的行为及其生理内部状态。我们建议利用我们的专业知识来剖析 神经回路和原理支配学习和适应性的“运动”控制内部器官功能。 我们将通过研究条件性胰岛素释放和条件性胰岛素释放来引领这一新的研究方向 免疫抑制，分别由胰腺和脾的神经支配介导。我们将利用 最新的病毒和RNA-SEQ方法以高分辨率定位一、二和三阶 脾和胰腺的神经支配。我们对这些器官的神经支配的初步解剖图谱 发现不同群体的腹膜-肠系膜神经节交感神经元支配胰腺。 对抗脾脏。值得注意的是，针对这些器官的胸段节前脊髓的大部分神经支配 从皮质出现：运动皮质，但也有感觉和前额叶。因此，我们假设 学习在条件作用后选择适当的内脏反应是由更高阶介导子的 大脑回路，遵循与运动反应相似的原理。我们建议使用这两种方法 识别和操纵下行神经群体活动的有针对性和不偏不倚的方法 负责学习控制脾和胰腺的功能。这一新的研究方向具有创新性。 但凭借我们的专业知识和先锋奖的支持，我们将帮助我们攻击这一新颖的研究领域。 重要的是，这项拟议的研究有可能在概念上将神经系统定位为“智能”。 机体动态平衡的调节器，因此以意想不到的方式影响健康-精神障碍，如 焦虑和抑郁，或者像中风这样的神经问题，都与生理异常有关。 这些大脑-内部器官的相互作用可能会产生一些状态。