A Novel Role for Nav1.1 in Mammalian Thermosensation
Nav1.1 在哺乳动物热感觉中的新作用
基本信息
- 批准号:10672978
- 负责人:
- 金额:$ 21.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:Action PotentialsAddressAdvisory CommitteesAffectAfferent NeuronsAttenuatedAwardBehaviorBehavioral AssayBiometryBiophysicsBrainCentral Nervous SystemClosure by clampCommunicationComplementDataDetectionDevelopmentDevelopment PlansDiseaseElectrophysiology (science)EnsureEnvironmentEsthesiaEtiologyExperimental DesignsGeneticGoalsHealthHumanHyperalgesiaHypersensitivityIn Situ HybridizationIn VitroIndividualInstitutionIon ChannelKnockout MiceKnowledgeLaboratoriesLearningMammalsMediatorMentorsMentorshipMolecularMusNatureNervous SystemNervous System PhysiologyNeuronsNeurosciencesOralPainPainlessPathway interactionsPeripheralPeripheral Nervous SystemPeripheral Nervous System DiseasesPhysiologicalPlayPositioning AttributePrevalenceProtein IsoformsResearchRoleSCN1A proteinSignal PathwaySignal TransductionSodium ChannelSpinal GangliaStatistical Data InterpretationStimulusTemperatureTestingTrainingTransgenic MiceTranslationsTrigeminal SystemWorkWritingallodyniaavoidance behaviorbehavior testbiophysical propertiescareercareer developmentchronic constriction injurycold temperatureconditional knockoutexperienceexperimental studyhuman diseasein vivoinnovationinsightmechanical allodyniamouse modelmutantnatural hypothermianerve injuryneurotransmissionnew therapeutic targetnoveloxaliplatinpain modelpainful neuropathypatch clampperipheral nerve damagepharmacologicpre-clinicalpreferenceprogramsreceptorskillsskin damagesomatosensorytooltranscriptome sequencingtransmission processvoltagewarm temperature
项目摘要
Project Summary. Detection of cold temperatures is fundamental for survival and allows for avoidance of
harmful environmental conditions that produce skin damage and eventually lead to hypothermia. Despite the
essential nature of cold sensing, the cellular and molecular mechanisms that transmit cold information in
peripheral dorsal root ganglion (DRG) sensory neurons remain poorly defined. Moreover, peripheral nerve
damage often results in cold allodynia, a hypersensitivity to mildly cold temperatures, and it is unclear whether
the mechanisms that transmit innocuous cold signals are highjacked or if conversely, separate signaling
pathways are engaged. In this proposal, we will address these critical questions by investigating a novel role for
the voltage-gated sodium channel, NaV1.1, in transmitting cold signals in a physiological context, as well as
during pain. Pharmacological inhibition of NaV1.1 in vitro role drastically attenuates action potential firing in
TRPM8-expressing neurons, providing evidence that NaV1.1 may be critical for cold-sensing in vivo. We have
developed new mouse models to test the central hypothesis that NaV1.1 channels transmit cold signals
specifically in TRPM8-expressing DRG neurons and become overactive during pain states that produce cold
allodynia. We will use an innovative combination of conditional knockout mouse lines, diverse somatosensory
behavioral assays, and mechanistic patch-clamp electrophysiological experiments from genetically identified
cold-sensing neurons to generate fundamental insights into peripheral mechanisms of cold transmission in both
health and disease. This work will advance our basic understanding of mammalian thermosensation and define
a new role for NaV1.1 in peripheral nervous system function. Importantly, completion of the proposed work is a
critical step towards my long-term goal of developing a leading research program that tackles basic and
translation questions about how the mammalian nervous system transmits and encodes thermal sensations. To
accomplish this goal, I have developed a detailed career development plan that includes a mentorship
committee, a scientific advisory committee, and targeted professional development activities that will focus on:
1) gaining expertise in behavioral assays and preclinical pain paradigms, 2) acquiring advanced biostatistical
analysis skills to ensure rigorous experimental design, 3) refining my written and oral scientific communication
skills, and 4) learning effective mentorship and lab management. The training received under this award will
uniquely poise me to develop a successful research program in the field of somatosensory neuroscience.
项目总结。探测寒冷的温度是生存的基础,并允许避免
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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Theanne Nicole Griffith其他文献
Theanne Nicole Griffith的其他文献
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{{ truncateString('Theanne Nicole Griffith', 18)}}的其他基金
Mapping the Pain Landscape: From Molecules to Medicine
绘制疼痛图谱:从分子到医学
- 批准号:
10609162 - 财政年份:2023
- 资助金额:
$ 21.78万 - 项目类别:
A Novel Role for Nav1.1 in Mammalian Thermosensation
Nav1.1 在哺乳动物热感觉中的新作用
- 批准号:
10525776 - 财政年份:2022
- 资助金额:
$ 21.78万 - 项目类别:
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