Cerebral cortical influences on the stomach

描述(申请人提供)：人们普遍认为大脑皮层对胃功能有很大的影响。然而，能够影响胃的皮质神经元的准确位置仍然很难确定。因此，为了理解认知事件如何影响健康和疾病中的胃功能，定义允许这种“大脑-肠道”相互作用的神经底物是至关重要的。狂犬病病毒的逆行跨神经元运输，加上仔细调整存活时间和使用神经切片，能够识别最直接影响大鼠胃自主神经每一分支的皮质区域。结果表明，大鼠内侧前额叶和外侧额叶皮质内大部分分离的皮质区网络与副交感或交感神经功能的下行控制有关。然而，与大鼠相比，灵长类动物大脑皮层这些区域的组织结构存在众所周知的差异，猴子和人类的大脑皮层区域在大鼠中完全不存在。导师实验室的其他实验已经证实，与大鼠相比，猴子大脑皮质影响交感神经控制的区域存在显著差异。因此，未来涉及自主神经控制的皮质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。这一职业发展奖的目标有三个。首先，申请者将获得神经解剖学技术方面的特定技能，使用非人类灵长类动物来定义胃的副交感和交感控制的皮质靶点(特定目标1)。其次，申请者将学习非侵入性操纵人类大脑皮层活动的技术。第三，申请者将在人类受试者身上应用这些技术，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(具体目标2)。这项职业发展建议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，重点是表征大脑-肠道相互作用的神经生物学基础。拟议的培训还奠定了坚实的基础，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，进行人类翻译生理学研究，并支持为难治性功能性胃肠道疾病患者开发基于大脑的新疗法。

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.