Molecular and genetic dissection of brain circuits controlling fever
控制发烧的脑回路的分子和遗传解剖
基本信息
- 批准号:10589104
- 负责人:
- 金额:$ 39.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAdipose tissueAffectAnimalsAreaAtlasesAttenuatedAwarenessBehaviorBehavioralBody TemperatureBrainCellsCollaborationsDataDedicationsDesire for foodDiagnosisDinoprostoneDissectionDorsalExhibitsFeverFluorescent in Situ HybridizationFutureGene ExpressionGenerationsGenesGeneticGoalsHumanHypothalamic structureImmediate-Early GenesImmuneImmune responseImmune signalingImmunologic FactorsIn SituInfectionInflammatoryInjectionsInnate Immune ResponseLethargiesLibrariesLipopolysaccharidesMedialMediatingMethodsMiddle HypothalamusModelingMolecularMusNervous SystemNeural PathwaysNeurogliaNeuronsOpticsPatientsPhysiologic ThermoregulationPhysiologicalPhysiologyPopulationPreoptic AreasProstaglandin ReceptorProstaglandinsProteinsRoleStereotypingSymptomsSynapsesTemperatureTestingThermogenesisUniversitiesViralacute infectionadaptive immune responseassociated symptomattenuationbehavioral responsecell typecytokineexperimental studyfightinggenetic approachgenetic informationgenetic technologyimaging modalityinducible Creinhibitorinsightneural circuitneuronal circuitrynovelnovel strategiesnovel therapeutic interventionparacrineparaventricular nucleuspathogenpromoterresponsesingle-cell RNA sequencingtherapeutic developmenttooltreatment strategy
项目摘要
PROJECT SUMMARY ABSTRACT
During an infection, animals exhibit adaptive changes in behavior and physiology aimed at increasing survival.
Although many causes of acute infection exist, a similar set of stereotyped symptoms occur, which includes
increased body temperature or fever, decreased appetite and increased lethargy. Both warm- and cold-blooded
animals generate a fever in response infection suggesting that fever circuits are hard-wired and highly
conserved, yet exactly how the nervous system alters body temperature and associated behavior in response to
infection remains unknown. We have identified a population of neurons in the preoptic area of the hypothalamus
that are highly activated following administration of inflammatory lipopolysaccharides (LPS). Due to the close
proximity between the organum vasculosum of the laminae terminalis (OVLT), where inflammatory cytokines
enter the brain to affect nearby cells, and neurons of the preotpic area regulating normal body temperature, and
our preliminary data, we propose that these newly identified LPS-sensitive neurons control fever initiation during
an immune response. We will use chemogenetic activation and cell ablation approaches to demonstrate that this
population plays a role in increasing body temperature and in affecting other fever-associated behaviors upon
LPS injection. Further, we have recently developed new approaches for molecular characterization of genetically
defined cell populations in situ using single-cell RNA sequencing (scRNA-seq) and multiplex, error-robust,
fluorescent in situ hybridization (MERFISH) to generate a spatially-resolved and functionally-aware atlas of the
preoptic area. We will apply a similar strategy to characterize fever-inducing neurons as well as surrounding non-
neuronal cell types that are likely to play a role in fever generation through paracrine mechanisms. Finally, we
propose to use viral-mediated tracing and functional tools to determine the direct and indirect circuit mechanisms
by which LPS-sensitive neurons and their targets exert control over body temperature and fever-related
behaviors. Our data will lead to a molecular and functional characterization of LPS-sensitive neurons in the
preoptic area and to a better understanding of how inflammatory sickness symptoms, such as fever and related
behavioral changes, are regulated in the brain. These efforts have direct implications for understanding the
mechanisms underlying human sickness, and may inform new therapeutic strategies for the treatment of fever
and associated symptoms.
项目摘要
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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Catherine Dulac其他文献
Catherine Dulac的其他文献
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{{ item.author }}
{{ truncateString('Catherine Dulac', 18)}}的其他基金
Odor trail tracking: a new paradigm to unveil algorithms and neural circuits underlying active sensation and continuous decision making
气味踪迹追踪:揭示主动感觉和持续决策背后的算法和神经回路的新范例
- 批准号:
10524245 - 财政年份:2022
- 资助金额:
$ 39.2万 - 项目类别:
Molecular and genetic dissection of brain circuits controlling fever
控制发烧的脑回路的分子和遗传解剖
- 批准号:
10373051 - 财政年份:2020
- 资助金额:
$ 39.2万 - 项目类别:
Systems-Level and in Situ Transcriptomics Deconstruction of Neural Circuits Underlying Sensorimotor Transformation in an Innate Behavior
先天行为中感觉运动转化的神经回路的系统级和原位转录组学解构
- 批准号:
10709855 - 财政年份:2020
- 资助金额:
$ 39.2万 - 项目类别:
Center for Integrated Multi-modal and Multi-scale Nucleome Research
综合多模式和多尺度核组研究中心
- 批准号:
10678954 - 财政年份:2020
- 资助金额:
$ 39.2万 - 项目类别:
Center for Integrated Multi-modal and Multi-scale Nucleome Research
综合多模式和多尺度核组研究中心
- 批准号:
10269034 - 财政年份:2020
- 资助金额:
$ 39.2万 - 项目类别:
Center for Integrated Multi-modal and Multi-scale Nucleome Research
综合多模式和多尺度核组研究中心
- 批准号:
10458025 - 财政年份:2020
- 资助金额:
$ 39.2万 - 项目类别:
Microcircuits underlying murine parental behavior
小鼠父母行为背后的微电路
- 批准号:
10461107 - 财政年份:2015
- 资助金额:
$ 39.2万 - 项目类别:
Microcircuits underlying murine parental behavior
小鼠父母行为背后的微电路
- 批准号:
10227959 - 财政年份:2015
- 资助金额:
$ 39.2万 - 项目类别:
Microcircuits underlying murine parental behavior
小鼠父母行为背后的微电路
- 批准号:
9751346 - 财政年份:2015
- 资助金额:
$ 39.2万 - 项目类别:
Microcircuits underlying murine parental behavior
小鼠父母行为背后的微电路
- 批准号:
10674853 - 财政年份:2015
- 资助金额:
$ 39.2万 - 项目类别:
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