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.
利用迷走神经运动神经元丰富的遗传多样性来解码脑肠通讯
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)
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STEPHEN Daniel LIBERLES其他文献
STEPHEN Daniel LIBERLES的其他文献
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{{ 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:
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