Cerebral cortical influences on the stomach

大脑皮质对胃的影响

• 批准号: 8858629
• 负责人: DAVID J LEVINTHAL
• 金额: $ 14.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8858629
• 关键词: Area; Base of the Brain; Bilateral; Brain; Cerebral cortex; Cerebrum; Cognitive; Complex; Coupled; Data; Development; Disease; Event; Foundations; Functional Gastrointestinal Disorders; Future; Gastrointestinal tract structure; Goals; Health; Human; K-Series Research Career Programs; Laboratories; Laboratory Animals; Lateral; Learning; Link; Location; Macaca; Maps; Measures; Medial; Mediating; Mentors; Monkeys; Motor Cortex; Nerve; Neurobiology; Neurons; Neurophysiology - biologic function; Organ; Patients; Physiologic Monitoring; Physiological; Primates; Rabies virus; Rattus; Refractory; Regulation; Research; Site; Stomach; Structure; System; Technical Expertise; Techniques; Time; Training; Translating; Vagotomy; Work; base; career; career development; conventional therapy; frontal lobe; gastrointestinal function; human subject; nerve supply; neurophysiology; neurotropic virus; nonhuman primate; novel; relating to nervous system; repetitive transcranial magnetic stimulation; research study; skills; skills training; time use; translational study

DESCRIPTION (provided by applicant): It is widely appreciated that the cerebral cortex exerts a powerful influence on stomach function. However, the precise location of cortical neurons capable of influencing the stomach remains poorly identified. Thus, defining the neural substrate allowing for such "brain-gut" interactions is critical to understanding how cognitive events influence stomach function in both health and disease. Retrograde transneuronal transport of rabies virus, coupled with careful adjustment of survival times and use of nerve sections, is capable of identifying the cortical areas that most directly influence each branch of the autonomic innervation of the rat stomach. The findings demonstrate that largely separate networks of cortical areas within the rat medial prefrontal and lateral frontal cortex are linked with the descending control of parasympathetic or sympathetic function. However, there are well-known differences in the organization of these regions of the cortex of primates compared to rats, with cortical areas present in monkeys and humans that are entirely absent in rats. Other experiments in the Mentor's laboratory have confirmed substantial differences in the cortical areas that influence sympathetic control in monkeys compared to the rat. Therefore, future neuroanatomical studies of the cortical networks involved in autonomic control will need to be performed in non-human primates. The goal of this career development award is three-fold. First, the applicant will acquire specific skills in neuroanatomical techniques using non-human primates to define the cortical targets for parasympathetic and sympathetic control of the stomach (Specific Aim 1). Second, the applicant will learn techniques for the non-invasive manipulation of cerebral cortical activity in humans. Third, the applicant will apply these techniques in human subjects to non- invasively manipulate the activity of identified cortical areas to influence the autonomic regulation of the stomach (Specific Aim 2). This career development proposal will provide the applicant with critical training and expertise necessary to establish an independent research career focused on characterizing the neurobiological basis of brain-gut interactions. The proposed training also establishes a strong foundation to support future exploration of the neuroanatomical basis of cortical-autonomic interactions, to pursue translational physiologic studies in humans, and to support the development of novel brain-based therapies for patients with refractory functional gastrointestinal disorders.

描述（由申请人提供）：人们普遍认为大脑皮层对胃功能有强大的影响。然而，能够影响胃的皮质神经元的精确位置仍然很难确定。因此，定义允许这种“脑-肠”相互作用的神经基质对于理解认知事件如何影响健康和疾病中的胃功能至关重要。狂犬病病毒的逆行跨神经元转运，加上仔细调整生存时间和使用神经节，能够识别最直接影响大鼠胃自主神经支配的每个分支的皮质区。研究结果表明，大鼠内侧前额叶和外侧额叶皮质内的皮质区在很大程度上独立的网络与副交感神经或交感神经功能的下降控制有关。然而，与大鼠相比，灵长类动物的这些皮层区域的组织存在着众所周知的差异，猴子和人类的皮层区域在大鼠中完全不存在。Mentor实验室的其他实验已经证实，与大鼠相比，猴子影响交感神经控制的皮层区域存在实质性差异。因此，未来的神经解剖学研究的皮层网络参与自主控制将需要在非人类灵长类动物。这个职业发展奖的目标有三个方面。首先，申请人将获得使用非人灵长类动物的神经解剖学技术的特定技能，以定义胃的副交感神经和交感神经控制的皮质靶点（特定目标1）。其次，申请人将学习人类大脑皮层活动的非侵入性操作技术。第三，申请人将在人类受试者中应用这些技术，以非侵入性地操纵所识别的皮层区域的活动，从而影响胃的自主调节（具体目标2）。该职业发展计划将为申请人提供必要的关键培训和专业知识，以建立一个独立的研究职业生涯，专注于表征脑肠道相互作用的神经生物学基础。拟议的培训还建立了一个坚实的基础，以支持未来探索皮质自主神经相互作用的神经解剖学基础，追求人类的转化生理学研究，并支持开发新的基于大脑的治疗难治性功能性胃肠疾病的患者。