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Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System

哺乳动物结肠神经系统的全面结构和功能图谱

基本信息

批准号：
10445460
负责人：
MILLION MULUGETA
金额：
$ 271.29万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-16 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10445460
关键词：
Comprehensive Structural Functional Mapping Mammalian

项目摘要

ABSTRACT The colon is the site of a multitude of disorders which are leading causes of morbidity and mortality and of significant financial burden. The colonic intrinsic (enteric) and extrinsic innervation play crucial role in regulating the secreto-motor, endocrine, immune functions and pain sensation. There has been increasing understanding of the neurochemical and electrophysiological properties, cell physiology, and functional roles of colonic enteric neurons and their interaction with the parasympathetic, sympathetic and sensory systems during the past decades. However, these data are derived largely from small animal studies and relevant knowledge in large animals and humans is lagging, which has hampered the development of effective therapies. Recent advances in cutting edge approaches including 3-D mapping, innovative viral tracing tools, and neuroimaging provide a means to obtain detailed information on neural circuits and related functions in large animals and human tissues, which has never been achieved before. The overall objective of the proposal is to provide a comprehensive and detailed structural and functional mapping of the intrinsic and extrinsic innervation of various regions of the colon in humans and the pig, as a relevant large animal model based on its structural and physiological similarities to humans. Mice will be utilized for studies involving transgenic, optogenetics and viral tracing approaches. This objective will be achieved by a concerted effort of world expert investigators who developed state-of-the art neuroanatomical, molecular, electrophysiological and functional approaches. Preliminary data obtained by the consortium team showed the feasibility to use CLARITY, high resolution confocal microscopy, viral tracing and optogenetics to provide detailed mapping of extrinsic nerve fibers, enteric circuitries and the expertise to probe human colonic enteric neurons electrophysiologically by fast and high resolution neuroimaging. In addition, the design of new microelectrode array and fiber optic technology has allowed quantifying motor patterns in response to nerve stimulation at a resolution level not attained before. The combined effort and multidisciplinary approaches will fill the gaps in current knowledge on colonic intrinsic and extrinsic neuronal circuits and cell-cell communication, especially in human tissues and pig, a large animal model ideally suited for translational applicability to patients. These findings will set the foundation for understanding neurocircuitry in this organ and will be critical for potential electroceutical interventions to treat colonic disorders.

摘要结肠是许多疾病的所在地，这些疾病是导致发病率和死亡率的主要原因巨大的经济负担。结肠内(肠)神经和外源性神经在调节中起着关键作用。分泌运动、内分泌、免疫功能和痛感。人们越来越多地了解到结肠肠道的神经化学和电生理特性、细胞生理学和功能作用神经元及其与副交感、交感和感觉系统的相互作用几十年。然而，这些数据主要是从小动物研究和相关知识中获得的动物和人类都处于滞后状态，这阻碍了有效疗法的开发。最新进展在包括3-D测绘在内的前沿方法中，创新的病毒跟踪工具和神经成像提供了获取大型动物和人体组织中神经回路和相关功能的详细信息的手段，这是以前从未实现过的。该提案的总体目标是提供一个全面和结肠不同区域的内在和外在神经支配的详细结构和功能图谱在人类和猪中，作为一个相关的大型动物模型，基于其结构和生理上的相似性人类。小鼠将被用于转基因、光遗传学和病毒追踪方法的研究。这这一目标将通过开发出最先进技术的世界专家调查人员的共同努力来实现神经解剖、分子、电生理和功能方法。获得的初步数据该联盟的团队展示了使用Clarity、高分辨率共聚焦显微镜、病毒跟踪和光遗传学，提供外源性神经纤维、肠道回路的详细图谱和探测的专业知识人结肠肠神经元电生理学快速高分辨率神经成像。此外，新的微电极阵列和光纤技术的设计使得量化电机模式成为可能神经刺激达到了前所未有的分辨率水平。综合努力和多学科这些方法将填补目前关于结肠内部和外部神经元回路和细胞-细胞的知识空白交流，尤其是在人类组织和猪中，这是一种非常适合翻译的大型动物模型对患者的适用性。这些发现将为理解这个器官中的神经回路和对于潜在的电击干预治疗结肠疾病将是至关重要的。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Online Artifact Cancelation in Same-Electrode Neural Stimulation and Recording Using a Combined Hardware and Software Architecture.

DOI：
10.1109/tbcas.2018.2816464
发表时间：
2018-06
期刊：
IEEE transactions on biomedical circuits and systems
影响因子：
5.1
作者：
Culaclii S;Kim B;Lo YK;Li L;Liu W
通讯作者：
Liu W

Piezo proteins: incidence and abundance in the enteric nervous system. Is there a link with mechanosensitivity?

DOI：
10.1007/s00441-018-2926-7
发表时间：
2019-03-01
期刊：
CELL AND TISSUE RESEARCH
影响因子：
3.6
作者：
Mazzuoli-Weber, Gemma;Kugler, Eva Maria;Schemann, Michael
通讯作者：
Schemann, Michael

Distinct patterns of myogenic motor activity identified in isolated human distal colon with high-resolution manometry.

DOI：
10.1111/nmo.13871
发表时间：
2020-10
期刊：
Neurogastroenterology and motility
影响因子：
3.5
作者：
Rosli RM;Heitmann PT;Kumar R;Hibberd TJ;Costa M;Wiklendt L;Wattchow DA;Arkwright J;de Fontgalland D;Brookes SJH;Spencer NJ;Dinning PG
通讯作者：
Dinning PG

The Transition From Rome III to Rome IV Irritable Bowel Syndrome: What We Gain and Lose.

从罗马 III 到罗马 IV 肠易激综合症的转变：我们得到和失去的。