Optogenetics
Consolato Sergi, M.D., Ph.D.
University of Alberta Hospital
12-10-14
Optogenetics
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Signals

Single-electrode recordings - Limitations
- Intracellular recordings: Only a few neurons and difficult in vivo
- Extracellular recordings: No capture information about subthreshold activity, bias against small cells, poorly defined cell identity

2-deoxyglucose (2DG) imaging (H3 or C14) - Limitations
- Visualization of active brain areas or neurons (post-mortem)
- Temporal resolution in min or hrs, not msec.
- ‘One-shot’ or ‘two-shot’ ways.
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Signals Cont’



PET/fMRI: poor spatio-temporal resolution,
hemodynamic transformation, drug receptor activation
patterns.
Optical Intrinsic Signal Imaging (OISI): hemodynamic
response in local capillaries related to local activity.
Voltage Sensitive Dye Imaging (VSDI): membrane
voltage, mostly sub-threshold activity in neurons and glia
cells.
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Optogenetics
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Optogenetics - Applications
 Fast depolarization / hyperpolarization of specific cells in
living animals
 Precise control and study of cell population dynamics
 The identification of causal positive and negative proof
with cell specificity
 Superior targeting & biocompatibility vs. electrical
stimulation
 Visual confirmation of target morphology using
fluorescent labeling
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Zhang F, Wang L-P, Boyden ES and Deisseroth K (2006)
Channelrhodopsin-2 and optical control of excitable cells.
Nature Methods 3(10): 785–792.
Chlamydomonas
reinhardtii- Wikipedia
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Zhang et al (2007) Multimodal fast optical
interrogation of neural circuitry. Nature 446: 633–641.
Archaea –
Wikipedia
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Halorhodopsin (NpHR)
•
Light-activated chloride pump
•
Archaebacterium Natronomas
pharaonis
•
•
22 mW/mm2 @ 560 +/- 27 nm
Inactivates after ~1 sec
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Current Status of Applications
Some published work in animals (e.g. mouse & zebrafish):
• Control and mapping of the function of motor cortex
• Expression restores light responses in retinal ganglion cells
• Dissection of Parkinson’s circuitry
• Dissection of role of DA neurons in behavioral conditioning
• Temporally precise in vivo control of intracellular signaling
• Potential control of epileptiform activity
• High-speed mapping of synaptic connectivity
• Dissection of a behavioral module in the spinal cord
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Take Home Message
Optogenetics is Nature Method of the Year 2010 and is
going to have more biology applications in the future!!!
...but how much is there to be discovered?
…is it up to us?
More Information on Pub Med and on
website of Dr. Chou Hung, Ph.D.
vision.ym.edu.tw/courses/methods/Presenta
tion2.ppt
12-10-14
Thank you
Optogenetics
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