Determining the role of noradrenergic heterogeneity in innate threat response
确定去甲肾上腺素能异质性在先天威胁反应中的作用
基本信息
- 批准号:10437607
- 负责人:
- 金额:$ 19.49万
- 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:2020-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AnatomyArousalAutopsyBehaviorBehavioralBehavioral ParadigmBiosensorBrainCalciumCell NucleusCellsComplementComplexComputer AnalysisComputer ModelsCuesDataDiseaseDissectionElectrophysiology (science)EmotionalExploratory BehaviorExposure toFoundationsFrightFundingFutureGene Expression ProfileGenesGoalsHeadHeterogeneityHumanImageIndividualK-Series Research Career ProgramsKnowledgeLearningLiteratureMental disordersMentorsMentorshipMethodsMicroscopeModelingMolecularMusNatureNeurobiologyNeuromodulatorNeuronsNeurotransmittersNorepinephrineOpticsPatternPhysiciansPhysiologyPopulationPost-Traumatic Stress DisordersPredatory BehaviorPrefrontal CortexPsychiatristPsychological reinforcementReportingResearchRoleScientistShelter facilitySourceStimulusStressStructureSupervisionSymptomsSystemTechniquesTrainingTraumaVisitVisualWorkbasecareercell typecomputer frameworkdifferential expressionexperienceexperimental studyimprovedin vivoinnovationlocus ceruleus structuremicroendoscopemind controlneural circuitneurochemistrynoradrenergicnorepinephrine systemnoveloptical imagingoptogeneticsprogramsresponsesingle cell sequencingsingle-cell RNA sequencingtranscriptome sequencingtranscriptomics
项目摘要
PROJECT SUMMARY / ABSTRACT
Studying the circuit basis of fear in psychiatric disorders has relied on learned associations
between stimuli and threatening experiences. Stimuli which are innately threatening represent
an alternative approach to this problem, and may elicit different neural circuit mechanisms to
promote survival. The neurotransmitter norepinephrine serves an important role in threat
response, and recent studies have demonstrated the existence of multiple subtypes of
norepinephrine cells within the locus coeruleus (LC). The scientific objective of this project is to
determine how subtypes of norepinephrine neurons in LC contribute to the encoding of threat,
so that in the future we can develop improved therapies for trauma-related disorders based on
that knowledge.
Our specific aims employ fluorescent biosensors of norepinephrine, miniature head-mounted
microscopes for recording LC norepinephrine cells, optogenetics, and single cell
transcriptomics. In our preliminary data, we identify a computational framework in which to
consider the problem of learning from innate threat, then show the feasibility of these
approaches. By employing these methods, we can collectively identify the relationship between
norepinephrine cell-types and the encoding of threat at molecular, cellular, and circuit scales.
This will generate a parts list for future studies into the nature of threat processing.
In addition to the proposed studies, this proposal develops a plan to train Dr. Kaye for an
independent research career as a circuit psychiatrist. This plan is mentored by Dr. Alex Kwan,
an expert in optical approaches to neural circuit dissection and computational approaches to
behavior, with the co-mentorship of Dr. Kerry Ressler, an expert in the neurobiology of
posttraumatic stress disorder and Dr. Ronald Duman, an expert in the neurobiology of stress.
This proposal relies on additional training in transcriptomics from Dr. Nenad Sestan, in
optogenetics from Dr. Ralph DiLeone, and in the physiology of the norepinephrine system from
Dr. Gary Aston-Jones.
项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
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Alfred P Kaye其他文献
Alfred P Kaye的其他文献
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{{ truncateString('Alfred P Kaye', 18)}}的其他基金
Determining the role of noradrenergic heterogeneity in innate threat response
确定去甲肾上腺素能异质性在先天威胁反应中的作用
- 批准号:
10651704 - 财政年份:2020
- 资助金额:
$ 19.49万 - 项目类别:
Circuit mechanisms for temporal filtering in the auditory thalamus
听觉丘脑中时间过滤的电路机制
- 批准号:
7809018 - 财政年份:2009
- 资助金额:
$ 19.49万 - 项目类别:
Circuit mechanisms for temporal filtering in the auditory thalamus
听觉丘脑中时间过滤的电路机制
- 批准号:
8117067 - 财政年份:2009
- 资助金额:
$ 19.49万 - 项目类别:
Circuit mechanisms for temporal filtering in the auditory thalamus
听觉丘脑中时间过滤的电路机制
- 批准号:
8308984 - 财政年份:2009
- 资助金额:
$ 19.49万 - 项目类别:
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