In Your Lab:
Looking at a Bright Future: Optogenetics In Your Lab
Have you heard about optogenetics yet?
If not, you soon will. Optogenetics techniques are sweeping neuroscience research. Named as the Method of the Year in 2010 by Nature Methods, optogenetics techniques are becoming widespread. The reason is clear: optogenetics offer the unprecedented ability to manipulate specific cells in real-time in freely behaving animals essentially by controlling a light switch. This allows for the dissection of intricate microcircuits that was previously impossible. Specific brain regions and neuronal types can be turned on and off at will. The effect on animal behavior of activation of a specific neuronal circuit can be observed immediately. This is an exciting and far-reaching opportunity to fine-tune functional and neuroanatomical knowledge.
The technology began as the result of long-time collaborations between Drs. Edward Boyden and Karl Deisseroth, among others (Boyden 2011). To better define the roles of individual neurons, these pioneers sought a way to drive or silence specific neurons embedded in intact brain circuitry. They found the way using an ion channel expressed in the green alga Chlamydomonas reinhardtii: channelrhodopsin-2 (ChR-2). ChR-2 is a cation-selective ion channel that is directly light-gated. In green alga, ChR-2serves to direct the alga to or from a light source to facilitate photosynthesis (Sineshchekov et al., 2002). When inserted into neurons, ChR-2 mediates light-driven spiking (Boyden et al., 2005). Viral transfection was first used to successfully express ChR-2 in neurons in vivo, thus opening the field of optogenetics to animal models (Arenkiel et al., 2007).
For in vivo use, an optical fiber is implanted into the brain for either acute or chronic use. Once the light is turned on, the cells expressing ChR-2 will be activated as the channel depolarizes the cell. Alternately, halorhodopsin expression is used to hyperpolarize a cell upon illumination, thus inactivating it at will (Tye and Deisseroth, 2012). In many cases, this will shorten the time frame required for behavioral experiments, as intervention with optogenetics requires no “wash-out” period, as pharmacological manipulations would (Tye and Deisseroth, 2012).
We had the good fortune to speak with Dr. Kay Tye, assistant professor at the Picower Institute of Learning and Memory at MIT, who incorporated optogenetic techniques into her postdoctoral work in the laboratory of Karl Deisseroth at Stanford University and has brought the techniques to her current laboratory. Much of her work now involves adapting classic behavioral tasks to a real-time, optogenetic paradigm for her studies defining the neural circuits involved in anxiety and depression. This research has huge potential, as psychiatric conditions such as these currently have inadequate available treatments, and optogenetic techniques can provide tremendous insight toward new targets for potential therapies.
In a paper (Tye et al., 2012) published this week in Nature, Tye et al. were able to directly test the hypothesis that the mesolimbic dopamine system is responsible for stress-induced depression and motivated behaviors. Using optogenetics, they directly activated dopaminergic neurons in the ventral tegmental area in freely behaving mice and rats. Activation of dopamine neurons in this region reduced depressive behaviors in the forced swim and tail suspension tests. Activation also increased sucrose preference in depressed animals. Inhibition of the neurons acutely induced depressive behaviors. As an example of the impressive methodological possibilities inherent in optogenetics, the authors were able to obtain electrophysiological recordings from the nucleus accumbens during the forced swim test, while simultaneously administering light to dopamine neurons in the ventral tegmental area and obtaining behavioral data using classical methods.
The field of optogenetics, while only in existence since 2005, has truly exploded in the past few years. “People with no background have been setting up optogenetics in their laboratories with success,” Dr. Tye said. In fact, with the right materials and knowledge, she says it is possible to add optogenetics techniques to a behavioral laboratory within a few months. To make this powerful technique even more accessible, the tools have traditionally been distributed freely by Drs. Deisseroth and Boyden, and helpful details are posted regularly at their websites: http://syntheticneurobiology.org/ and http://www.stanford.edu/group/dlab/optogenetics/
The future looks bright for optogenetics research. The literature is filling up with papers using the techniques. Specific neuronal circuits for many brain systems are being delineated as we speak, and the potential for precise understanding of pathological conditions is huge. And it isn’t just for neuroscience either: optogenetics are even being used to engineer better muscle tissue for robots (Sakar et al., 2012). We wish the Tye laboratory and everyone embarking on optogenetic research the best of luck, and can’t wait to see and hear more from you!
Arenkiel BR, Peca J, Davison IG, Feliciano C, Deisseroth K, Augustine GJ, Ehlers MD, Feng G. (2007). In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron. Apr 19;54(2):205-18.
Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. Sep;8(9):1263-8.
Boyden ES. (2011). A history of optogenetics: the development of tools for controlling brain circuits with light. F1000 Biol Rep. 3:11.
Method of the Year 2010. (2011). Nature Methods: 8,1. Published online 20 December 2010. doi:10.1038/nmeth.f.321
Sakar MS, Neal D, Boudou T, Borochin MA, Li Y, Weiss R, Kamm RD, Chen CS, Asada HH. (2012). Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. Lab Chip. Dec 7;12(23):4976-85.
Sineshchekov OA, Govorunova EG, Spudich JL. (2002). Photosensory functions of channelrhodopsins in native algal cells. Photochem Photobiol. Mar-Apr;85(2):556-63.
Tye KM, Deisseroth K. 2012. Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci. Mar 20;13(4):251-66.
Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB,Deisseroth K. (2012). Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature. Dec 12.
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