By: Andrew Huhn, 3rd year PhD candidate in the Neuroscience Program

Optogenetics is one of the most significant advances in neuroscience in the last decade. The very concept of optogenetics appears to come straight from a science fiction novel: we can control the brain with a laser! Okay, so that’s a bit of an overstatement, but not by much.

Optogenetics allows scientists to selectively excite or inhibit discrete areas of an animal brain using a beam of light. Moreover, scientists can control a single type of neuron within that region, providing fine-tuned control that was unachievable with earlier methods. But how exactly is this accomplished? And what implications does this have on biomedical research?

Before we talk about the medical implications of such a tool, we first need a better understanding of optogenetics.

You may remember an earlier post I wrote about the science of vision, i.e. how the retina turns a photon of light into a biochemical signal using the protein rhodopsin. Well, back in the 2002, scientists at the Max-Planck Institute in Germany were studying algae and discovered channelrhodopsin, a protein that allows algae to find the right depth in sea water based on wavelengths of light.

While rhodopsin allows us to perceive light (and thus the world around us), channelrhodopsin allows algae to perceive water depth using light: the deeper they go, the less light there is. These proteins control ion channels, making them capable of generating an action potential in neurons.

By replicating the gene for this protein, and using a lenti-virus to insert it into an animal (work first done by the Diesseroth lab at Stanford), scientists were able to take control of a subtype of neurons simply by shining light on them.

But how does the beam of light get through the skull?

Generally, mice undergo stereotaxic surgery to mount an LED light or optical fiber. A particular area of the brain can then be “switched on” by light alone. Even more exciting is that, using genetic selection processes, different types of neurons can be selectively turned on, offering excellent spatial resolution.

It is this resolution that allows scientists to study regions of the brain, such as the prefrontal cortex, with high specificity.

How will optogenetics contribute to functional brain mapping?

It will help scientists to better understand neural components of behavior, autonomic function (such as stress response), and sensory/motor skills. In fact, it has already been used in several studies focused on reward, addiction, and motor control. For example, a recent publication in the journal Addiction Biology uses optogenetics to extinguish cocaine use in addicted rats; by selectively inhibiting neurons in the brain’s “reward system,” addictive behavior was abolished.

So, controlling animal brains is great, but are there any direct medical implications for optogenetics?

The future?

Some scientists believe optogenetics could be used to directly treat disease in humans. In the future, it may be possible to use optogenetics to treat neurodegenerative disorders. One example is Parkinson’s disease.

Treatment of Parkinson’s disease already involves alternative methods such as deep brain stimulation, which targets a small population of neurons; it’s not far off to think that optogenetics could offer a more refined approach. While deep brain stimulation uses a probe to excite the brain region where neurons are dying, optogenetic therapy could target the individual type of neurons and leave the rest of that region unaffected.

Optogenetics is quickly becoming one of the most powerful tools in neuroscience. It will not only shed light on functional brain mapping, it will increase our understanding of complex neural diseases potentially leading to revolutionary treatments.

References:

Boyden ES et al. (2005). “Millisecond-timescale, genetically targeted optical control of neural activity” Nature Neuroscience 8 (9): 1263-8.

Nagel G et al. (2002). “Channelrhodopsin-1: a light gated proton channel in green algae” Science 296 (5577): 2395-8.

Stefanik MT et al. (2013). “Optogenetic inhibition of cocaine seeking in rats” Addiction Biology 18 (1): 50-3.