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


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OptogeneticsEd Boyden, MITvideoA light switch for neurons



Optogenetics

Optogenetic Molecular Machinary ToolsBrian YC, et al. Sci Trans Med 2013.


Optogenetics

www.optogenetic.org

Karl Deisseroth, StanfordEd Boyden, MITFeng Zhang, MIT


Optogenetics - ApplicationInspire Me!

Optogenetics - Application& Other applications

Nature 2010Nature 2012


Optogenetic Behavioral Control

D1, D2 selectively expressed ChR2(by D1-cre and D2-cre mice)

Kratvitz AV, et al. Nature, 2010


Cre ChR2-eYFP System.16

Optogenetic Behavioral Control

Direct PathwayIndirect PathwayKratvitz AV, et al. Nature, 2010


Optogenetic Behavioral ControlKratvitz AV, et al. Nature, 2010

Bilateral Stimulation Indirect PathwayBilateral Stimulation Direct Pathwayin 6-OHDA Mouse


Optogenetics Mind Control

Nature 2012


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)


Optogenetic Mind ControlLiu X. et al. Nature 2013

ChR2 StainingPositive control : KA induced c-fos expression


Optogenetic Mind Control

Conditioned group vs. controlLiu X. et al. Nature 2013


Optogenetic Mind ControlLiu X. et al. Nature 2013Fear Condition Specific Neurons of Hippocampus

Light activated the specific neurons

Fear Feeling


Optogenetics - Application

Localized Stimulation : Where?

Complex NetworkOptogenetic Imaging


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.


Optogenetic ImagingGlobal Level Mapping

Nature 2010.

J Neurosci 2013.


Optogenetic Imaging: fMRIAAV5-CaMKII Promotor :: ChR2 Cell Specific ChR2 Expression(CaMKII expressing cells)

Lee JH, et al. Nature 2010.

ChR2 IHC


Optogenetic Imaging: fMRIOptogenetic Stimulation Positive BOLD signal at stimulation site (Motor Cortex)



Optogenetic Imaging: fMRIOptogenetic Stimulation Positive BOLD signal at Thalamus (Effective Connectivity)



Optogenetic Imaging: FDG PETOptogenetic FDG PET

AAV2-hsyn-ChR2-EFYPControl: AAV2-GFPThanos PK, et al. J Neurosci 2013.


Synapsin-132

Optogenetic Imaging: FDG PETNeural connectivity with Nucleus Accumbens (right)

C-Fos Expression in Hypermetabolic regionsThanos PK, et al. J Neurosci 2013.


Optogenetic ImagingEarly-Stage TechniqueEffective Brain MappingMap for Where We Should Stimulate

Harrison TC et al. Neuron 2012.


Biomarker & Making Biology Future Direction

Biomarker for OptogeneticsOptogenetic Imaging : Biomarker & Guideline for InterventionBiologic Phenomenon

Observation& Intervention


Biomarker for Optogenetics

Packer AM, et al. Nat Neurosci 2013.Optogenetic PETOptogenetic fMRIArtificial Feedback


Biomarker for OptogeneticsKrook-Magnuson et al. Nat Commun 2013.

Artificial Feedback


Biomarker for Optogenetics

Krook-Magnuson et al. Nat Commun 2013.


Beyond Brain : Synthetic Physiology

Light-induced signal cascadeMelanopsin .NFAT GLP-1Haifeng Ye et al. Science, 2011



Haifeng Ye et al. Science, 2011Light-induced signal cascadeControl Blood Glucose LevelIn Diabetes Mice


Beyond Brain : Synthetic Physiology Synthetic PhysiologyGlucose Level, HTN, etc.Role of Biomarkers

Artificial FeedbackChow BW and Boyden Ed, et al. Science 2011


Beyond Brain : Synthetic Physiology Imaging BiomarkerGene Expression : Reporter GeneNeural Activity : PET/MRI

Carbon nanohorn

Miyako et al. PNAS, 2012




Imaging & Synthetic Physiology High-throughput neural activation control by fMRI

Lee JH, et al. J Neurosci Method 2013.


AmyEntoAcbCPAcbSSThaHpPLRImaging & Synthetic Physiology Feedback


Beyond BenchAAV : Gene TherapyLimitation of Optical Fiber

Heat-opened channel + Ferritin NP + RF Stanley SA, et al. Science 2012


V1 : Modified TRPV147

Take Home MessageMaking Biology EraSynthetic PhysiologyA Key for making medicine : Biomarker

Lets Prepare to Meet Avatar Human

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