CH391L/S13/Optogenetics

Introduction to Optogenetics

"Before we can find the answers, we need the power to ask new questions." -Karl Deisseroth

In essence, optogenetics is a neural modulation technique used to control neurons in vitro for the purpose of affecting the physiology of neural circuits and ultimately behavior of the studied organism. However, in recent studies, optogenetic techniques have been used to modify nonneuronal tissues, such as cardiac tissue and beta cells, willfully controlling the respective cell-specific roles. Although the implications of optogenetics seem like a panacea for many genetic diseases, much of the field is new; in terms of therapeutics, research is regretfully far behind. Currently, optogenetic techniques are attempted mostly on rodent specimens since primate studies lack profound electrophysical and behavior effects. Optogenetic is widely associated with neuroscience research- sometimes thought as the synergy between neuroscience and synthetic biology. Current optogenetically-related research aims to ascertain brain function of multiple neural circuits, but future endeavors include gene therapy for neurodegenerative diseases and neuroprosthetics.

The basis is optogentics is quite simple. The neuron in question is spliced with a specific opsin gene carried by viral vector, usually a modified lentivirus. Subsequently, the encoded opsin attached to the cell membrane. Opsin are photosensitive G protein receptors or ion channels that are induced by a specific wavelength of visible light via fiber optic cable or optrode. In turn, the opsin undergoes a conformational change, eliciting a change in membrane potential. For neuronal cells, changes in membrane potential give rise to action potentials. The strength of the depolarizing current (incoming positive charged ions) is encoded in the frequency of the action potentials generated. Furthermore, synapses (gap junction between neurons) can conduct spatial or temporal summation. Even neuronal cells can be silenced with hyperpolarizing current (incoming negative or outgoing positive charged ions). In short, optogenetics provides neuroscientists with an “on/off” switch for targeted neurons.

History

"The brain is a world consisting of a number of unexplored continents and great stretches of unknown territory." - Santiago Ramón y Cajal

Applications of Optogenetics

IGEM Take-home Message

http://2012.igem.org/Team:Washington/Optogenetics http://2006.igem.org/wiki/index.php/University_of_Texas_2006 http://2006.igem.org/wiki/index.php/UT_Austin_2005 http://2004.igem.org/austin.cgi

References

1. Mei Y and Zhang F. Molecular tools and approaches for optogenetics. Biol Psychiatry. 2012 Jun 15;71(12):1033-8. DOI:10.1016/j.biopsych.2012.02.019 |
2. Yizhar O, Fenno L, Zhang F, Hegemann P, and Diesseroth K. Microbial opsins: a family of single-component tools for optical control of neural activity. Cold Spring Harb Protoc. 2011 Mar 1;2011(3):top102. DOI:10.1101/pdb.top102 |
3. Zemelman BV, Lee GA, Ng M, and Miesenböck G. Selective photostimulation of genetically chARGed neurons. Neuron. 2002 Jan 3;33(1):15-22. DOI:10.1016/s0896-6273(01)00574-8 |
4. LaLumiere RT. A new technique for controlling the brain: optogenetics and its potential for use in research and the clinic. Brain Stimul. 2011 Jan;4(1):1-6. DOI:10.1016/j.brs.2010.09.009 |
5. Doroudchi MM, Greenberg KP, Liu J, Silka KA, Boyden ES, Lockridge JA, Arman AC, Janani R, Boye SE, Boye SL, Gordon GM, Matteo BC, Sampath AP, Hauswirth WW, and Horsager A. Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. Mol Ther. 2011 Jul;19(7):1220-9. DOI:10.1038/mt.2011.69 |
6. Boyden ES, Zhang F, Bamberg E, Nagel G, and Deisseroth K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. 2005 Sep;8(9):1263-8. DOI:10.1038/nn1525 |