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December 19, 2014 | By:  Daniel Kramer
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Controlling Neurons Using Light

I hoped I would never have to say this, but we don't use only 10% of our brains. There could be many reasons why this idea started and continues to this day. It could come from early studies of animal brain dissections that didn't lead to noticeable changes in behavior. Whatever the cause, I think the perpetuation of this myth represents something larger, that the brain still feels a bit like black magic.

Initial studies into the specific functions of different regi

ons of the brain involved investigating lesions in the brain and correlating phenotypes with the region that was lost. A good example of this is the work done by Brenda Milner and her patient H.M. H.M. suffered severe damage to his hippocampus and entorhinal cortex of his brain. From her research, it was determined that the hippocampus and the surrounding areas play a vital role in forming new memories. But, as is true so often with the brain, this doesn't paint the complete picture of these regions. There is rarely a hard and fast specificity within the brain. The boundaries between regions are hardly distinct and strict, and there is certainly overlap.

While a broad map of the brain is essential, part of the reason why the brain remains a mystery is the vast amount of complexity involved in neuronal communications. We need to know specifics about how individual neurons interact with each other and create circuits. This will give us a higher definition picture of what exactly is going on between our ears.

In order to better understand the mysteries of the brain, neuroscientists are using optogenetics. This involves engineering neuronal proteins so researchers can use light to activate or deactivate these neurons. Although the field has been building momentum for nearly a decade, it is still flying under the radar of those outside of the field. Optogenetics is based around genetically engineered ion channels. Ion channels, among other things, sit in the receiving portion of a neuron called the dendrite. These ion channels are usually closed, but when they come in contact with neurotransmitters released from neighboring neurons at synapses, they open and allow action potentials to continue through the receiving neuron.

To make the ion channels sensitive to light, scientists use specific molecules that are photoactivatable; they change their shape or activity when light is shined on them. They can attach one side of the photoactivatable molecule to a neurotransmitter and the other to the ion channel that responds to the neurotransmitter. When they hit the activatable molecule with light, it changes its conformation, bends, and puts the neurotransmitter into the receptor site of the ion channel, activating and opening it. Another way scientists engineer ion channels with photoactivatable molecules is by modifying them to contain a protein named channelrhodopsin, which interacts with a protein in the brain called retinol. Retinol changes its conformation when hit with light, and this change activates channelrhodopsin, opening the ion channel it is associated with.

These techniques are very powerful and allow for the control of small sets of specific neurons at the timescales that researchers are interested in. They can open and close channels by shining different wavelengths of light on the neurons to alter the conformation of the photoactivatable molecules. A scientist can pick whether they want a channel that halts activity or activates activity. By using particular promoters, they can also express the engineered channels in very specific neurons in the brain. Activating or inactivating the neurons with light enables researchers to observe how the selected neurons lead to certain firing patterns or even control certain behaviors in animals.

As an example, scientists recently used channelrhodopsin in the cortical amygdala of mice. By activating and inactivating these neurons using light, they could turn on and off fear responses to smells that are instinctively frightening to mice, like fox odors. Their work showed that the cortical amygdala plays a role in innate odor responses, but not learned odor responses. This is just one recent example of many that show the power in the field of optogenetics.

The brain is most certainly still a mystery, but enabling us to work out small circuits within the brain, optogenetics provides a groundwork for understanding how neurons interact with each other. The biotechnology discussed is still a burgeoning field, and there will undoubtedly be further advances. Maybe the brain won't remain a black box for long.


Szobota, S. & Isacoff, E. Y. Optical Control of Neuronal Activity, Annual Reviews of Biophysics 39, 329-348 (2010). (Image is augmented from Figure 1 of this publication)

Root, C. M. et al. The participation of cortical amygdala in innate, odour-driven behaviour. Nature 515, 269-273 (2014).

Image credits:

the picture above comes from the Szobota & Isacoff paper in Annual Reviews of Biophysics.

1 Comment
December 27, 2014 | 02:36 AM
Posted By:  Eric Sawyer
Dan-- Nice inaugural post! I'm glad the blog is in capable hands, and best of luck! --Eric
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