Cerebral cortical influences on the stomach

描述（申请人提供）：大脑皮层对胃功能的强大影响已被广泛认识。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。狂犬病毒逆行经神经元转运，加上仔细调整存活时间和使用神经切片，能够确定最直接影响大鼠胃自主神经支配各分支的皮质区域。研究结果表明，在大鼠内侧前额叶皮层和外侧前额叶皮层中，很大程度上独立的皮质区域网络与副交感神经或交感神经功能的下行控制有关。然而，与大鼠相比，灵长类动物的这些皮质区域的组织结构存在众所周知的差异，猴子和人类的皮质区域在大鼠中完全不存在。曼托实验室的其他实验已经证实，与大鼠相比，猴子在影响交感神经控制的皮层区域存在实质性差异。因此，未来涉及自主神经控制的皮层网络的神经解剖学研究将需要在非人类灵长类动物中进行。这个职业发展奖项的目标有三个方面。首先，申请人将获得使用非人类灵长类动物的神经解剖学技术的特定技能，以确定胃的副交感神经和交感神经控制的皮层目标（特定目标1）。其次，申请人将学习非侵入性操作人类大脑皮层活动的技术。第三，申请人将这些技术应用于人类受试者，非侵入性地操纵已识别的皮质区域的活动，以影响胃的自主调节（特定目标2）。这份职业发展计划将为申请人提供必要的培训和专业知识，以建立一个独立的研究生涯，专注于描述脑-肠相互作用的神经生物学基础。拟议的培训也为支持未来探索皮层-自主神经相互作用的神经解剖学基础，追求人类翻译生理学研究，以及支持难治性功能性胃肠疾病患者的新型脑基础疗法的发展奠定了坚实的基础。

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.