Genetically encoded indicators for large-scale sensing of neuromodulatory signaling in behaving animals
用于大规模感知行为动物神经调节信号的基因编码指标
基本信息
- 批准号:9767296
- 负责人:
- 金额:$ 96.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-08-01 至 2021-06-30
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAcuteAddressAffectAffinityAmino AcidsAnatomyAnimal BehaviorAnimalsArousalArrestinsAttentionBehaviorBehavioralBiological AssayBody RegionsBrainBrain regionCalciumCatecholaminesCell NucleusCell SurvivalCellsCognitionCognitiveColorCommunicationCommunitiesComputer SimulationCorpus striatum structureCyclic AMPDimensionsDirected Molecular EvolutionDiseaseDopamineDorsalElectric StimulationElectrophysiology (science)EmotionsEvolutionFlow CytometryG-Protein-Coupled ReceptorsGTP-Binding ProteinsGenerationsGlutamatesHealthHumanImageIn VitroKineticsLeadLigandsLinkMeasurementMental DepressionMental disordersMicrodialysisMolecularMusNervous system structureNeurodegenerative DisordersNeurogliaNeuromodulatorNeuronsNeuropeptidesNeurosciencesNoiseNorepinephrineOpioidOpticsOutputParkinson DiseasePathway interactionsPatternPeptide Signal SequencesPerceptionPeriodicityPharmaceutical PreparationsPlayPopulationProcessPropertyProteinsReportingResearch PersonnelResolutionRoleScaffolding ProteinSchizophreniaSensitivity and SpecificitySerotoninSignal TransductionSiteSite-Directed MutagenesisSliceSpecificitySpinalSpinal cord injurySubstantia nigra structureSurfaceSynapsesSynaptic TransmissionSystemTechniquesTestingTimeValidationViralWhole-Cell RecordingsWorkaddictionarrestin 2basebehavior influencebehavior testbeta-arrestincalcium indicatordorsal horndrug of abuseextracellulargamma-Aminobutyric Acidhigh throughput screeningin vivoinsightlocus ceruleus structureminimally invasivemonoaminemouse modelmultidisciplinarynanonervous system disorderneural circuitneuronal patterningneuroregulationnoveloperationrecruitsensorspatiotemporalsuccesstemporal measurementtraffickingtwo photon microscopyvirtualvoltage
项目摘要
Brain functions are executed by intricately coordinated networks of neurons, whose modes of operation are
highly sensitive to a constellation of neuromodulators. More specifically, neuromodulators such as dopamine,
norepinephrine, serotonin, and acetylcholine exert dramatic control over global brain processes such as
arousal, attention, emotion, or cognitive perception. Altered neuromodulator signaling has been linked to
neurological and psychiatric disorders such as Parkinson's disease, schizophrenia, depression and addiction.
Similarly, opioid neuropeptides play important roles in the modulation of cognition and behavior. While the
anatomical structures that produce neuromodulatory signals are well known, little is known about the spatial
and temporal evolution of these signals in the innervated brain regions. This is because current measurement
techniques, such as microdialysis or cyclic voltammetry, lack the spatial or temporal resolution (and often the
molecular specificity) to resolve respective signals. This technical challenge has been a long-standing barrier
to our understanding of how neuromodulation alters neural circuit function in order to influence behavior. To
address this challenge, this project will develop, validate, and disseminate novel genetically encoded
fluorescent proteins for large-scale optical measurement of monoamine neuromodulator and opioid
neuropeptide signaling in behaving animals, by bringing together a multi-disciplinary team of investigators with
unique and complementary expertise. These sensor proteins have the potential to revolutionize neuroscience
in a way similar to genetically encoded indicators for calcium, glutamate, and voltage, which are now in
widespread use. Combined with calcium and voltage imaging, neuromodulator sensors will reveal how these
systems impinge on cellular and circuit function. In particular, proposed sensors will enable minimally invasive,
high-resolution, long-term, and direct measurement of neuromodulator and neuropeptide signaling at synaptic,
cellular, and system levels. Sensors for neuromodulatory signaling have remained elusive for a long time. Our
team recently developed a first generation of genetically encoded indicators for serotonin (5-HT),
norepinephrine (NE), and dopamine (DA) that can report nano- to micromolar concentration changes with high
spatial and temporal resolution. Building on this work, the following specific aims are proposed: 1) Optimize
and diversify genetically encoded sensors for the monoamines using computational modeling, directed
evolution and high-throughput screening; 2) Develop and optimize genetically encoded sensors for opiate
neuropeptides using novel protein scaffolds; and 3) Systematically validate the novel neuromodulator and
neuropeptide sensors in acute brain slices and behaving animals. Together, this work will provide the
neuroscience community with a wide range of well-characterized multi-color indicators for probing the
functional role of neuromodulators and neuropeptides in regulating neural circuit function and behavior in both
health and disease.
大脑功能是由复杂协调的神经元网络执行的,其运作模式是
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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Axel Nimmerjahn其他文献
Axel Nimmerjahn的其他文献
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{{ truncateString('Axel Nimmerjahn', 18)}}的其他基金
Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior
将快速时间尺度神经元-星形胶质细胞通信与神经回路功能和行为联系起来
- 批准号:
10693171 - 财政年份:2021
- 资助金额:
$ 96.08万 - 项目类别:
Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior
将快速时间尺度神经元-星形胶质细胞通信与神经回路功能和行为联系起来
- 批准号:
10294804 - 财政年份:2021
- 资助金额:
$ 96.08万 - 项目类别:
Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior
将快速时间尺度神经元-星形胶质细胞通信与神经回路功能和行为联系起来
- 批准号:
10461226 - 财政年份:2021
- 资助金额:
$ 96.08万 - 项目类别:
Elucidating cellular activity patterns underlying spinal cord function
阐明脊髓功能背后的细胞活动模式
- 批准号:
9912873 - 财政年份:2019
- 资助金额:
$ 96.08万 - 项目类别:
Elucidating cellular activity patterns underlying spinal cord function
阐明脊髓功能背后的细胞活动模式
- 批准号:
10381704 - 财政年份:2019
- 资助金额:
$ 96.08万 - 项目类别:
Genetically encoded indicators for large-scale sensing of neuromodulatory signaling in behaving animals
用于大规模感知行为动物神经调节信号的基因编码指标
- 批准号:
9533713 - 财政年份:2017
- 资助金额:
$ 96.08万 - 项目类别:
Overcoming barriers in the study of in vivo spinal cord function
克服体内脊髓功能研究的障碍
- 批准号:
8739332 - 财政年份:2013
- 资助金额:
$ 96.08万 - 项目类别:
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