Biochemists rejoice as they receive optogenetic control of signaling pathways

18 March 2009 by Noah Gray, posted in Uncategorized

Optogenetic tools have already changed the face of neuroscience research. From its humble beginnings as a cation-selective algal channel, channelrhodopsin and its variants have been employed to do many things:

But all these experiments involved a direct manipulation of the electrical circuitry connecting various brain nuclei or cortical layers, making this channel the darling of the electrophysiologists’ world. What about the biochemist? Yeah, that guy/gal pouring neurotoxic acrylamide gels to assist in the dissection of signaling pathways, asking which phosphorylated protein was connected to another, either physically or functionally. They like light too, don’t they? (at least when we let them out of the basement lab…). (cont.)
Well fret no longer, Mr/s. Biochemist. The lab of Karl Deisseroth has introduced to you a brand new set of optogenetic tools designed for the manipulation of signaling pathways with the specificity of genetic targeting and the precision of light control. In their new paper, published AOP in Nature today, Deisseroth and colleagues demonstrate the use of chimeric GPCRs — with the external bits of rhodopsin for light activation and the internal bits of either the β2-adrenergic receptor or the α1-adrenergic receptor. These adrenergic receptors are coupled to different G-protein signaling pathways, which can influence excitability in neurons and alter the threshold to fire action potentials. Since only the internal portions of the adrenergic receptors are used, there are no additional signaling responses by the chimeras when catecholamines are released, only upon light exposure.
In the paper, the authors demonstrate that these tools are not only functional in vitro, but also in vivo. In a really cool experiment, the OptoXRs (as they are called) were expressed in the nucleus accumbens, known to play a role in reward-based signaling in the brain. A conditioned place preference (CPP) experiment was carried out where the signaling pathways in the NuAcc neurons were turned on using a fiber optic cable every time the freely moving mouse was in a particular corner of the cage. This was designed to mimic reward. In subsequent trials, the mice spent a significantly longer period of time in the corner where the light bursts were delivered, the same behavior rodents display when they receive a drug or food reward in a particular spot. So not only did the optogenetic activation influence behavior, it essentially acted as a surrogate for reward. In theory, from the reward circuitry perspective, the mouse could not discern actual reward from reward circuit activation. Man, does this open up a lot of doors for future work…
Only time will tell what other neuroscience labs will be able to accomplish with these new toys, but at least now the biochemists can join the light-activated party.

Airan, R., Thompson, K., Fenno, L., Bernstein, H., & Deisseroth, K. (2009). Temporally precise in vivo control of intracellular signalling Nature DOI: 10.1038/nature07926

4 Responses to “Biochemists rejoice as they receive optogenetic control of signaling pathways”

  1. Mo Costandi | Permalink

    Very cool stuff, and a nice summary.

    Sooner or later, someone will come up with a wireless, light-emitting implant made with carbon nanotubes.

  2. Noah Gray | Permalink

    That’s all you want, Mo? Well then, check out what these guys are doing. From what I’ve seen, this is some of the closest to even hinting at what you describe. The optrode is actually quite cool.

  3. Mo Costandi | Permalink

    I’m just saying that wireless implants would be the next logical step. Should’ve know that someone’s already working on it – thanks for the link.

  4. namrata shinde | Permalink

    Leave apart the war between biochemists and electrophysiologists… this matter must be interesting to both groups. It’s very much exciting and promising. We can literally sieve brains of experimental animals expressing these genetically encoded optical tools (‘optoXRs’). And the way it can be used to provide a temporally precise non invasive control of activities in desired brain areas is very encouraging.

    This could have therapeutic applications if we could use it in humans or animals not expressing the genes for ‘optoXRs’. Can a method or system or something be developed to insert these chimeric GPCRs in membranes of desired neuronal populations in animals not modified genetically; without dissecting the brain? If it can be done safely we’ll enjoy a host of therapeutic applications. For example in depression we can keep the reward systems functioning for longer time; we can reach the depths of violent cruel brains and teach them to associate pleasure of others to their reward systems. We can use this to treat host of psychiatric disorders like kleptomania, phobias; neurological diseases like epilepsy… something like a magic stick.

    Well, this was my daydreaming. I’m not in a position to suggest ways to do it. Not an expert in neuroscience, I’m just a student. But I’m extremely curious and interested in this research. You say this was published on 18 Mach 2009; one year has passed since then any new advancement in this area of studies? Any other researches related to this?


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