Leveraging the Rich Genetic Diversity of Vagal Motor Neurons to Decode Brain-to-Gut Communication
利用迷走神经运动神经元丰富的遗传多样性来解码脑肠通讯
基本信息
- 批准号:10443804
- 负责人:
- 金额:$ 70.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-17 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAcidsAddressAffectAfferent NeuronsAreaAssimilationsBackBrainCatalogsCellsCephalicCommunicationCommunitiesContractsDigestionDuodenumEatingEndocrineEnteralFeedbackFiberFoodFundusFutureGallbladderGastrointestinal PhysiologyGene Expression ProfileGenesGeneticGenetic EngineeringGenetic MarkersGenetic VariationHormonesInvestigationKnowledgeLogicMapsMeasuresMicroscopyMotorMotor NeuronsMusNeuronsNeurosciencesNutrientOrganPancreasPancreatic PolypeptideParasympathetic Nervous SystemPeptide YYPhysiologicalPhysiologyPlayProcessRNARabiesReflex actionRegulationRelaxationRestRoleSignal TransductionSpecific qualifier valueStomachStretchingTechnical ExpertiseTechnologyTimearmbasecholinergic neurondorsal motor nucleusexperiencegenetic approachmind controlmotor controlmouse geneticsneural circuitoptogeneticspancreatic juicerecombinaserelating to nervous systemresponsesingle-cell RNA sequencingtooltranscriptomics
项目摘要
Leveraging the Rich Genetic Diversity of Vagal Motor Neurons to Decode Brain-to-Gut Communication
The motor vagus was originally treated as a single entity – the principal arm of the parasympathetic ‘rest and
digest’ response. Over time, as diverse vagal actions were uncovered, it came to be viewed as a composite of
many functionally discrete motor units, which are themselves differentially regulated. Indeed, neurons
originating in the dorsal motor nucleus of the vagus (DMV) control at least three different processes in the
stomach (secretion of acid, contraction and relaxation), two in the pancreas (exocrine and endocrine secretion)
and also contraction of the gallbladder. Likewise, these motor units are regulated by many inputs – by cephalic
signals that anticipate eating to prepare the gut and body for food, and by vagal sensory neurons and gut
hormones that, via vago-vagal and endocrine-vagal reflexes, coordinate digestion and assimilation of nutrients.
A major impediment to understanding the neural basis for this regulation, however, is that it is not known how
many functionally discrete vagal motor units actually exist, and, more importantly, there is a lack of any means
for selectively mapping and manipulating the different motor units. These issues have held the field back.
This Multi-PI R01 application addresses this problem by: a) using single cell RNA profiling to catalogue the
different subtypes of DMV motor neurons and identify genetic markers that specify each subtype, b) by
assembling or generating “gene marker”-recombinase mice that enable recombinase-dependent exploration of
the DMV neuron subtypes, and then c) by utilizing these mice to determine each neuron’s respective target
organ(s) and downstream enteric neuron(s), the role each DMV neuron plays in regulating GI physiology, and
the ways the DMV neuron subtypes are uniquely regulated by CNS afferents, vagal afferents and hormones.
The Lowell and Liberles labs are ideally suited to this effort because their knowledge and areas of technical
expertise are highly relevant, and also very complementary. The Lowell lab has: a) preliminarily discovered
genetically distinct subsets of vagal motor neurons (via single cell RNA sequencing), b) is converting this
information into neuron subtype-specific recombinase mice, and c) has expertise in using recombinase mice
and recombinase-dependent technologies to investigate neural circuits. The Liberles lab, on the other hand
has: a) discovered functionally and genetically distinct vagal sensory neurons – the afferent arms of the vago-
vagal reflexes, b) has extensive experience with manipulating activity of vagal fibers and assessing effects on
gastrointestinal physiology, and c) has preliminarily discovered distinct subsets of the downstream enteric
neurons. Combined, the Lowell and Liberles labs are well poised to deconvolute vagal motor function.
利用迷走运动神经元丰富的遗传多样性破译脑与肠道之间的通讯
运动迷走神经最初被认为是一个单一的实体--副交感神经休息的主臂和
摘要的回应。随着时间的推移,随着不同的迷走神经动作被发现,它开始被视为
许多功能离散的电机单元,它们本身是差异化调节的。事实上,神经元
起源于迷走神经背侧运动核(DMV)控制着大脑中至少三个不同的突起。
胃(胃酸的分泌、收缩和松弛),胰腺有两种(外分泌和内分泌)
以及胆囊壁的收缩。同样,这些运动单位也受到许多输入的调节--由头
预计进食的信号,以准备肠道和身体的食物,并通过迷走神经和肠道
荷尔蒙通过迷走神经和内分泌迷走神经的反射,协调营养的消化和吸收。
然而,理解这一调节的神经基础的一个主要障碍是不知道它是如何
实际上存在许多功能离散的迷走神经运动单位,更重要的是,缺乏任何手段
用于选择性地映射和操纵不同的电机单元。这些问题阻碍了这一领域的发展。
此多PI R01应用程序通过以下方式解决此问题:a)使用单细胞RNA分析来编目
DMV运动神经元的不同亚型,并识别指定每个亚型的遗传标记,b)通过
组装或产生“基因标记”-重组酶小鼠,使重组酶依赖于探索
DMV神经元亚型,然后c)通过利用这些小鼠来确定每个神经元各自的靶点
器官(S)和下游肠神经元(S),每个DMV神经元在调节胃肠道生理中所起的作用,以及
DMV神经元亚型受中枢神经传入、迷走神经传入和激素的独特调节方式。
Lowell和Liberles实验室非常适合这项工作,因为他们的知识和技术领域
专业知识是高度相关的,也是非常互补的。洛厄尔实验室已经:a)初步发现
基因上不同的迷走运动神经元亚群(通过单细胞RNA测序),b)正在将这种
向神经元亚型特异性重组酶小鼠提供信息,以及c)在使用重组酶小鼠方面具有专业知识
和重组酶依赖的技术来研究神经回路。另一方面,自由实验室
有:a)发现了功能和遗传上截然不同的迷走神经感觉神经元--迷走神经的传入臂--
迷走神经反射,b)在处理迷走神经纤维的活动和评估对
胃肠生理学,以及c)初步发现了下游肠道的不同亚群
神经元。加在一起,洛厄尔和利伯勒斯的实验室已经做好了解除迷走神经运动功能的准备。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
STEPHEN Daniel LIBERLES其他文献
STEPHEN Daniel LIBERLES的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('STEPHEN Daniel LIBERLES', 18)}}的其他基金
Area postrema neurons that mediate nausea-associated behaviors
介导恶心相关行为的后区神经元
- 批准号:
10440136 - 财政年份:2022
- 资助金额:
$ 70.67万 - 项目类别:
Area Postrema Neurons that Mediate Nausea-Associated Behaviors
介导恶心相关行为的后区神经元
- 批准号:
10573276 - 财政年份:2022
- 资助金额:
$ 70.67万 - 项目类别:
Leveraging the Rich Genetic Diversity of Vagal Motor Neurons to Decode Brain-to-Gut Communication
利用迷走神经运动神经元丰富的遗传多样性来解码脑肠通讯
- 批准号:
10206129 - 财政年份:2019
- 资助金额:
$ 70.67万 - 项目类别:
Leveraging the Rich Genetic Diversity of Vagal Motor Neurons to Decode Brain-to-Gut Communication
利用迷走神经运动神经元丰富的遗传多样性来解码脑肠通讯
- 批准号:
10653096 - 财政年份:2019
- 资助金额:
$ 70.67万 - 项目类别:
Leveraging the Rich Genetic Diversity of Vagal Motor Neurons to Decode Brain-to-Gut Communication
利用迷走神经运动神经元丰富的遗传多样性来解码脑肠通讯
- 批准号:
10019337 - 财政年份:2019
- 资助金额:
$ 70.67万 - 项目类别:
Charting vagal circuits containing glucagon-like peptide 1 receptor
绘制含有胰高血糖素样肽 1 受体的迷走神经回路
- 批准号:
9222742 - 财政年份:2016
- 资助金额:
$ 70.67万 - 项目类别:
Sensory biology of respiratory control neurons in the vagus nerve
迷走神经呼吸控制神经元的感觉生物学
- 批准号:
9077705 - 财政年份:2016
- 资助金额:
$ 70.67万 - 项目类别:
Sensory biology of respiratory control neurons in the vagus nerve
迷走神经呼吸控制神经元的感觉生物学
- 批准号:
9273635 - 财政年份:2016
- 资助金额:
$ 70.67万 - 项目类别:
Charting vagal circuits containing glucagon-like peptide 1 receptor
绘制含有胰高血糖素样肽 1 受体的迷走神经回路
- 批准号:
9095676 - 财政年份:2016
- 资助金额:
$ 70.67万 - 项目类别:
相似国自然基金
具有抗癌活性的天然产物金霉酸(Aureolic acids)全合成与选择性构建2-脱氧糖苷键
- 批准号:22007039
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
海洋放线菌来源聚酮类化合物Pteridic acids生物合成机制研究
- 批准号:
- 批准年份:2019
- 资助金额:10.0 万元
- 项目类别:省市级项目
手性Lewis Acids催化的分子内串联1,5-氢迁移/环合反应及其在构建结构多样性手性含氮杂环化合物中的应用
- 批准号:21372217
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
对空气稳定的新型的有机金属Lewis Acids催化剂制备、表征与应用研究
- 批准号:21172061
- 批准年份:2011
- 资助金额:30.0 万元
- 项目类别:面上项目
钛及含钛Lewis acids促臭氧/过氧化氢体系氧化性能的广普性、高效性及其机制
- 批准号:21176225
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
基于Zip Nucleic Acids引物对高度降解和低拷贝DNA检材的STR分型研究
- 批准号:81072511
- 批准年份:2010
- 资助金额:31.0 万元
- 项目类别:面上项目
海洋天然产物Makaluvic acids 的全合成及其对南海鱼虱存活的影响
- 批准号:30660215
- 批准年份:2006
- 资助金额:21.0 万元
- 项目类别:地区科学基金项目
相似海外基金
Lipid nanoparticle-mediated Inhalation delivery of anti-viral nucleic acids
脂质纳米颗粒介导的抗病毒核酸的吸入递送
- 批准号:
502577 - 财政年份:2024
- 资助金额:
$ 70.67万 - 项目类别:
CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids
职业:高度快速、灵敏的核酸纳米机电检测
- 批准号:
2338857 - 财政年份:2024
- 资助金额:
$ 70.67万 - 项目类别:
Continuing Grant
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 70.67万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 70.67万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Synthetic analogues based on metabolites of omega-3 fatty acids protect mitochondria in aging hearts
基于 omega-3 脂肪酸代谢物的合成类似物可保护衰老心脏中的线粒体
- 批准号:
477891 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Operating Grants
Metabolomic profiles of responders and non-responders to an omega-3 fatty acids supplementation.
对 omega-3 脂肪酸补充剂有反应和无反应者的代谢组学特征。
- 批准号:
495594 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrated understanding and manipulation of hypoxic cellular functions by artificial nucleic acids with hypoxia-accumulating properties
具有缺氧累积特性的人工核酸对缺氧细胞功能的综合理解和操纵
- 批准号:
23H02086 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 70.67万 - 项目类别:
Grant-in-Aid for Scientific Research (C)