Opto- and chemogenetic neural activity recording with diverse reporters
使用不同的记者记录光和化学遗传学神经活动
基本信息
- 批准号:10373012
- 负责人:
- 金额:$ 34.32万
- 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:2019-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:BehaviorBindingBrainCalmodulinCell NucleusCellsColorCytoplasmEngineeringEnzymesExposure toFeelingGenesGeneticGenetic TranscriptionGoalsHealthHumanImageKineticsLightLinkMembraneMethodsMicroscopeMicroscopyNatureNeuronsPeptide HydrolasesPharmaceutical PreparationsPopulationProteinsReporterReportingResolutionSpecimenStimulusSubstrate InteractionSystemTEV proteaseTechniquesThinkingTimeTobacco DependenceVariantbasebrain volumedesignenzyme activityexperimental studyfluorophoregenetic approachimprovedmind controlneural circuitneural patterningoperationoptogeneticsreconstitutionreconstructionrelating to nervous systemresponsesmall moleculestemsuccesstobacco etch virustool
项目摘要
PROJECT SUMMARY/ABSTRACT
The brain's control of our thoughts, feelings, and behaviors stems from neural circuits, which perform logical
operations based on the temporal patterns of neural activity and the connectivity of the neurons as the circuit
traverses the brain. Recent studies have produced many strategies for visualizing and controlling a circuit's
neural activity. In some cases, specialized microscopy systems have enabled imaging of entire brain volumes
on the timescale of neural activity and during behavior, enabling the reconstruction of neural circuitry at cellular
resolution. However, recording neural activity from whole brain volumes to reconstruct neural circuitry is a
significant challenge when working with larger brains, less specialized microscopes, or stimuli and behaviors
that are not conducive to concurrent imaging. In these situations, strategies that enable permanent recording
of neural activity during defined time windows for later readout would be highly beneficial.
In this proposal, we describe an approach for permanent recording of neural activity using Ca2+-dependent
enzymatic activation of genetically encoded substrates. We focus our efforts on the Tobacco Etch Virus (TEV)
protease because it does not have endogenous substrates in vertebrate systems, it has been employed in
living neurons, it has been extensively re-engineered to record interactions between diverse binding partners,
and its split fragments dissociate in the absence of reconstituting binding partners. We propose a strategy for
engineering a Ca2+-dependent TEV protease that involves a split version of the enzyme with each half attached
to the Ca2+-binding partners calmodulin and M13. These TEV fragments are designed so that in the absence of
neural activity they will remain separate and inactive, but in the presence of neural activity and high Ca2+, the
association of calmodulin and M13 will permit TEV reconstitution and enzyme activity. Once active, the split
TEV protease can cleave a variety of genetically encoded substrates that link TEV protease activity with
transcription of a desired gene or direct creation of a fluorophore. Thus, using this strategy will enable users to
control neurons activated by a given stimulus or behavior (e.g., by expressing optogenetic tools in response to
TEV activity) or to visualize neurons active during distinct epochs (e.g., by expressing a photoactivatable
mOrange in response to one stimulus or behavior, photoconverting the mOrange, and then recording the
second stimulus). Finally, the split TEV protease and substrate interactions can be controlled with modular
optogenetics tools to provide precise temporal control over the time period of recording.
项目总结/文摘
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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Scott T. Laughlin其他文献
Hierarchical assembly in PLA-PEO-PLA hydrogels with crystalline domains and effect of block stereochemistry.
PLA-PEO-PLA 水凝胶中的分层组装,具有晶域和嵌段立体化学效应。
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Xuechen Yin;David R. O. Hewitt;Alyssa N Preston;L. Heroux;M. Agamalian;Suan P. Quah;Bingqian Zheng;Andrew J. Smith;Scott T. Laughlin;R. B. Grubbs;S. Bhatia - 通讯作者:
S. Bhatia
Stable cyclopropene-containing analogs of the amino acid neurotransmitter glutamate
氨基酸神经递质谷氨酸的稳定的含环丙烯类似物
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:1.8
- 作者:
Pratik Kumar;Wei Huang;David Shukhman;Frank M Camarda;Scott T. Laughlin - 通讯作者:
Scott T. Laughlin
Scott T. Laughlin的其他文献
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{{ truncateString('Scott T. Laughlin', 18)}}的其他基金
Opto- and chemogenetic neural activity recording with diverse reporters
使用不同的记者记录光和化学遗传学神经活动
- 批准号:
10133168 - 财政年份:2019
- 资助金额:
$ 34.32万 - 项目类别:
Opto- and chemogenetic neural activity recording with diverse reporters
使用不同的记者记录光和化学遗传学神经活动
- 批准号:
10582675 - 财政年份:2019
- 资助金额:
$ 34.32万 - 项目类别:
Opto- and chemogenetic neural activity recording with diverse reporters
使用不同的记者记录光和化学遗传学神经活动
- 批准号:
9902558 - 财政年份:2019
- 资助金额:
$ 34.32万 - 项目类别:
Examining the neural circuit for an instinctive olfactory-induced behavior in lar
检查 lar 中本能嗅觉诱发行为的神经回路
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8576294 - 财政年份:2013
- 资助金额:
$ 34.32万 - 项目类别:
Examining the neural circuit for an instinctive olfactory-induced behavior in lar
检查 lar 中本能嗅觉诱发行为的神经回路
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8680205 - 财政年份:2013
- 资助金额:
$ 34.32万 - 项目类别:
Examining the neural circuit for an instinctive olfactory-induced behavior in lar
检查 lar 中本能嗅觉诱发行为的神经回路
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8789878 - 财政年份:2013
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