neurobiology - synthetic biology (2014)
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Synthetic Neurobiology & Medical ImagingChoi Hongyoon
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Stimulation
Specific Behavior
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Avatar ProtocolMaryam M, et al. Nat Commun 2013
CONTENTS
Making Biology Paradigm ShiftInspiring Me!Optogenetics - ApplicationsNuclear Medicine & Synthetic NeurobiologyImaging Optogenetics
Future DirectionBiomarker & Making Biology
Paradigm shiftMaking Biology
Paradigm ShiftBiologic PhenomenonBiologic PhenomenonObservation
Observation& InterventionMAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Paradigm Shift
Designed by HumanDesigned by God
How to Decode?How to Control?
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
: Microscopic View : Miro 8
Paradigm Shift
Channel Rhodopsin
Blue light induced neuronal activationEd Boyden et al. Nat Neurosci 2005
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
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OptogeneticsEd Boyden, MITvideoA light switch for neurons
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetics
Optogenetic Molecular Machinary ToolsBrian YC, et al. Sci Trans Med 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetics
www.optogenetic.org
Karl Deisseroth, StanfordEd Boyden, MITFeng Zhang, MIT
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetics - ApplicationInspire Me!
Optogenetics - Application& Other applications
Nature 2010Nature 2012
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Behavioral Control
D1, D2 selectively expressed ChR2(by D1-cre and D2-cre mice)
Kratvitz AV, et al. Nature, 2010
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Cre ChR2-eYFP System.16
Optogenetic Behavioral Control
Direct PathwayIndirect PathwayKratvitz AV, et al. Nature, 2010
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Behavioral ControlKratvitz AV, et al. Nature, 2010
Bilateral Stimulation Indirect PathwayBilateral Stimulation Direct Pathwayin 6-OHDA Mouse
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetics Mind Control
Nature 2012
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Mind ControlLiu X. et al. Nature 2013
C-fos induced tTA (Transgenic Mice)+tTA-TRE activation ChR2 expression (AAV)Doxycycline : TRE inhibitorC-fos : Early neural activation proteinFC: fear condition (Shock)
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Mind ControlLiu X. et al. Nature 2013
ChR2 StainingPositive control : KA induced c-fos expression
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Mind Control
Conditioned group vs. controlLiu X. et al. Nature 2013
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Mind ControlLiu X. et al. Nature 2013Fear Condition Specific Neurons of Hippocampus
Light activated the specific neurons
Fear Feeling
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetics - Application
Localized Stimulation : Where?
Complex NetworkOptogenetic Imaging
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Imaging optogeneticsNuclear Medicine & Synthetic Neurobiology
Optogenetics based large-scale activation mapStill in its infancyA key for decoding brain network
Optogenetic Imaging
Obamas Brain InitiativeWe still havent unlocked the mystery of the three pounds of matter between our earsMAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic ImagingMicroscopic Level Mapping
Lim DH, et al. Front Neurosci 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic ImagingGlobal Level Mapping
Nature 2010.
J Neurosci 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Imaging: fMRIAAV5-CaMKII Promotor :: ChR2 Cell Specific ChR2 Expression(CaMKII expressing cells)
Lee JH, et al. Nature 2010.
ChR2 IHC
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Imaging: fMRIOptogenetic Stimulation Positive BOLD signal at stimulation site (Motor Cortex)
Lee JH, et al. Nature 2010.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Imaging: fMRIOptogenetic Stimulation Positive BOLD signal at Thalamus (Effective Connectivity)
Lee JH, et al. Nature 2010.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic Imaging: FDG PETOptogenetic FDG PET
AAV2-hsyn-ChR2-EFYPControl: AAV2-GFPThanos PK, et al. J Neurosci 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Synapsin-132
Optogenetic Imaging: FDG PETNeural connectivity with Nucleus Accumbens (right)
C-Fos Expression in Hypermetabolic regionsThanos PK, et al. J Neurosci 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Optogenetic ImagingEarly-Stage TechniqueEffective Brain MappingMap for Where We Should Stimulate
Harrison TC et al. Neuron 2012.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Biomarker & Making Biology Future Direction
Biomarker for OptogeneticsOptogenetic Imaging : Biomarker & Guideline for InterventionBiologic Phenomenon
Observation& Intervention
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Biomarker for Optogenetics
Packer AM, et al. Nat Neurosci 2013.Optogenetic PETOptogenetic fMRIArtificial Feedback
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Biomarker for OptogeneticsKrook-Magnuson et al. Nat Commun 2013.
Artificial Feedback
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Biomarker for Optogenetics
Krook-Magnuson et al. Nat Commun 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond Brain : Synthetic Physiology
Light-induced signal cascadeMelanopsin .NFAT GLP-1Haifeng Ye et al. Science, 2011
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond Brain : Synthetic Physiology
Haifeng Ye et al. Science, 2011Light-induced signal cascadeControl Blood Glucose LevelIn Diabetes Mice
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond Brain : Synthetic Physiology Synthetic PhysiologyGlucose Level, HTN, etc.Role of Biomarkers
Artificial FeedbackChow BW and Boyden Ed, et al. Science 2011
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond Brain : Synthetic Physiology Imaging BiomarkerGene Expression : Reporter GeneNeural Activity : PET/MRI
Carbon nanohorn
Miyako et al. PNAS, 2012
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond Brain : Synthetic Physiology
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Imaging & Synthetic Physiology High-throughput neural activation control by fMRI
Lee JH, et al. J Neurosci Method 2013.
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
AmyEntoAcbCPAcbSSThaHpPLRImaging & Synthetic Physiology Feedback
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
Beyond BenchAAV : Gene TherapyLimitation of Optical Fiber
Heat-opened channel + Ferritin NP + RF Stanley SA, et al. Science 2012
MAKING BIOLOGYINSPIRING MENM&SYNTHETIC BIOLOGYFUTURE
V1 : Modified TRPV147
Take Home MessageMaking Biology EraSynthetic PhysiologyA Key for making medicine : Biomarker
Lets Prepare to Meet Avatar Human
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