Brain control of internal organ function

大脑控制内脏器官功能

• 批准号: 10679652
• 负责人: Rui M. Costa
• 金额: $ 118.82万
• 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/10679652
• 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.

抽象的 即使是简单的动作（例如伸展手臂），对行为的适应性控制也至关重要。 我们的实验室结合使用了神经系统中许多神经元群的激活。 解剖学、遗传学、光学和行为方法来揭示动物如何移动并学习控制 然而，适应性反应不仅通过肌肉发挥作用，还通过其他方式发挥作用。 例如，计划采摘苹果不仅会引发肌肉活动，还会引发期望。 因此，适应性行为需要协调。 我们建议利用我们的专业知识来剖析有机体的行为及其生理内部状态。 神经回路和控制内脏器官功能的学习和适应性“运动”控制的原理。 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。 我们将分别利用胰腺和脾脏的神经支配介导的免疫抑制。 最先进的病毒和 RNA-seq 方法以高分辨率绘制一阶、二阶和三阶图谱 脾脏和胰腺的神经支配我们对这些器官的神经支配进行了初步的解剖图绘制。 研究表明不同群体的腹腔-肠系膜神经节交感神经元支配胰腺 值得注意的是，胸节前脊髓的大部分神经支配都针对这些器官。 从皮层中出现：运动皮层，还有感觉皮层和前额皮层，因此我们在这方面进行竞争。 在高阶调节的调节下学习选择内脏器官的适当反应 大脑回路，并遵循与运动反应相似的原则，我们建议同时使用这两种方法。 有针对性和公正的方法来识别和操纵下降神经群体的活动 负责脾脏和胰腺功能的学习控制这项新的研究是创新的。 但可以通过我们的专业知识进行跟踪，并且先锋奖的支持将帮助我们攻克这个新颖的研究领域。 重要的是，拟议的研究有可能从概念上将神经系统定位为“智能”系统 机体稳态的调节者，从而以意想不到的方式影响健康——精神障碍，如 焦虑和抑郁，或中风等神经系统问题，与异常的生理现象有关 这些状态可能是从这些大脑与内部器官的相互作用中出现的。