optogenetics: what you see is what you think syeda anika imam, amandeep taank, dana zaitoun, seo...
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Optogenetics: What you see is what you think
Syeda Anika Imam, Amandeep Taank, Dana Zaitoun, Seo Hyun Lee
http://www.livescience.com/29340-optogenetics-brain-research-breakthrough-nsf-bts.html
PHM142 Fall 2015Coordinator: Dr. Jeffrey HendersonInstructor: Dr. David Hampson
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What is Optogenetics?• Optogenetics is a branch of biotechnology which combines genetic engineering with optical methods
• Research tool to obtain insights into complex tissue function such as Parkinson’s disease
• Optogenetics is subdivided into:
• Sensors: monitor neural circuits
• Effectors: manipulate neural circuits
• Basic concept: expressing a light activated ion channel in a specific group of cells such as neurons then illuminating the cells to control activity
http://web.stanford.edu/group/dlab/optogenetics/
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How it works: Neurons
•Every neuron has a pump and channel proteins that control the flow of ions across the membrane
•Resting membrane potential is negative
•When a signal arrives, an influx of Na+ ions causes depolarization
http://antranik.org/synaptic-transmission-by-somatic-motorneurons/
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Photosensory Molecules
•Molecules that convert light into electricity
•Can be naturally occurring or chemically modified Channelrhodopsin (ChR2) - found in algae Chlamydomonas reinhardtii Halorhodopsin (NpHR) – found in archaeon Natronomonas pharaonic
•Genes that code for these molecules can be delivered by:- Transfection (introducing nucleic acids into cells, non-viral methods in eukaryotic cells)- Viral transduction- Creation of transgenic animal lines
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Channelrhodopsin•Cation channel
•Activated by blue light (470nm)
•Allows Na+ influx across the membrane and depolarizes the neuron, thus activating it
•Acts as the on switch
Halorhodopsin•Chloride pump
•Activated by yellow light (580 nm)
•Triggers influx of Cl- which hyperpolarizes the cell and inhibits the neuron
•Acts as the Off switch
Pastrana, E. (2011). Optogenetics: Controlling cell function with light. Nature Methods, 8(1), 24-25. DOI:10.1038/nmeth.f.323
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Deisseroth, K. (2011). Optogenetics. Nature Methods, 8(1), 26-29.
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Parkinson’s Disease (PD)
• Neurological disorder due to degeneration of neurons that produce dopamine (dopaminergic neurons)
• Decrease in dopamine leads to abnormal brain activity, and diseases such as PD• Symptoms include:
• tremors• bradykinesia• stiff muscles• loss of involuntary movements• speech problems• other motor problems
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Optogenetic Application to PD Treatment
• Cell replacement therapy: integrating engineered dopamine releasing (DA) neurons into the brain network
• Engineered DA neurons express halorhodopsin• in vitro conditions, release of dopamine in DA neurons inhibited when exposed to light• after grafting the DA neurons into lesion-induced PD mice, the subjects showed substantial
recovery of motor symptoms, but when yellow light shines on DA neurons, motor recovery of mice was lost
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Deep Brain Stimulation (DBS)
Deisseroth, K., & Tye, K. (2012). Optogenetic investigation of neural circuits underlying brain disease in animal models. Neuroscience Nat. Rev., 13, 251-266.
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Currently used to investigate…
• Schizophrenia• Anxiety and Mood Disorders• Addiction• Autism
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Pros and Cons
Pros of Optogenetics Cons of OptogeneticsExcellent spatial and temporal solution Viral infections and exogenous proteins can lead to
structural abnormalities/toxicity
Significant experimental control Damage to surrounding tissue
Can be applied to many fields
Can be used as disease models
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References(2010). Optogenetics. Research Papers of the Max Planck Society, 24-25.
Butler, J. (2012). Optogenetics: Shining a light on the brain. Bioscience Horizons, 5, 1-8. doi: 10.1093/biohorizons/hzr020
Deisseroth, K. (2011). Optogenetics. Nature Methods, 8(1), 26-29.
Deisseroth, K., & Tye, K. (2012). Optogenetic investigation of neural circuits underlying brain disease in animal models. Neuroscience Nat. Rev., 13, 251-266.
Dugue, G.P. et., al. (2012). A comprehensive concept of optogenetics. Progress in brain research, 196, 1-28.
Fowler, C.D., et., al. (2014). Using Optogenetics and Designer Receptors Exclusively Activated by Designer Drugs (DREADDS). 1-3.
Lamballais, S. (2013). Optogenetics and its Applications in Psychology: Manipulating the Brain Using Light. Journal of European Psychology Students, 4, 87-100.
Liu, X., Tonegawa, S. (2010). Optogenetics 3.0. Cell, 141, 22-24.
Steinbeck, J.A., Choi, S.J., Mrejeru, A., Ganat, Y., Deisseroth, K., Sulzer, D., Mosharov, E.V., Studer, L. (2015). Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model. Nature Biotechnology, 33 (2): 204-209. doi: 10.1038/nbt.3124.
Pastrana, E. (2011). Optogenetics: Controlling cell function with light. Nature Methods, 8(1), 24-25. DOI:10.1038/nmeth.f.323
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Summary• Optogenetics is a branch of biotechnology which combines genetic engineering with optical methods
to observe and control the function of genetically targeted groups of cells with light
• Channelrhodopsin = ion channel that is activated by blue light and depolarizes a neuron
• Halorhodopsin = Chloride channel that is activated by yellow light and inhibits neuronal action
• Parkinson’s disease (PD): neurological disorder due to degeneration of neurons that produce
dopamine
• Cell replacement therapy uses halorhodopsin to test validity
• Deep Brain Stimulation (DBS) is a current therapy used for PD, where you have a pace maker that
stimulates the brain
• Optogenetics is used to determine the mechanism of DBS
• Pros: excellent spatial and temporal resolution
• Cons: can lead to structural abnormalities and toxicity