Optogentics

Imagine you are going out with your shy single friend to a party, he / she is talking to a nice potential match, but your friend starts to melt down. Your role as the wing person is to save the conversation and you just do that, not with starting a new topic or saying something interesting, but simply by switching the light on and off again and instantly your friend returns to his/ her normal state. Is that totally freaky science fiction? Actually, it's not.

Genetics and optics were united to form the new field of optogentics to control events within chosen cells of living organisms. However, thanks to ethical regulations, the above scenario would not be seen in the foreseeable future. On the other hand, realistically, this approach could allow us to understand more about and treat complicated diseases such as anxiety and Parkinson disease.

So how does it work? Optogenetics is based on a simple concept, which is the transfer of certain genes that have the ability to invoke light response in cells from one organism to another. If we concentrate on the use of optogentics in the nervous system, we find that the brain consists of neuronal cells that form a circuit, continuously, passing information from one hub to another in the form of neuronal signals also known as action potentials. Action potentials are formed through the passage of ions from and into the cell membrane through special channels called ion channels.

An interesting protein called Channelrhodopsin-2 (ChR2) can open an ion channel if activated by light. This protein is added to the mammalian brain through an ingenious method:

1. The protein (in the form of its DNA sequence) is added to a virus genome.

2. The virus is injected into the mammalian (mouse) brain.

3. The virus (carrying our interesting gene) integrates its genome with the mouse genome.

4. The mouse genome machinery translate its own genome including the virus genome and our gene of interest into proteins making the particular area in the mouse brain in which this gene ends up in responsive to light.

Thus, we can control it by switching the light (in that case, blue light at 480 nm) on or off to induce action potential. Delivering the light inside the brain is done through fine electrodes that are surgically implemented in the brain region we want to investigate.

A nice example to illustrate the applications of this technique is its use in treating anxiety symptoms in mice. This is done by controlling the centromedial (CeM) part of the brain. This part when excited initiates anatomic and behavioural responses associated with fear. CeM itself is controlled by the basolateral amygdala (BLA) neurons that excite the centrolateral (CeL) neurons which in turn form a feed-forward loop to CeM neurons. The problem is that BLA controls other parts of the brain and up till recently there weren't any available methods that allowed us to control the signal coming from BLA to CeM, without affecting other behaviour aspects of the patients. In 2011 researchers at the bioengineering department at Stanford University found that optogenetics can actually control this pathway. By inhibiting the particular BLA terminals associated with CeL using light they could increase anxiety in the investigated mice. On the other hand, astonishingly, they found that optogenetic stimulation of the same region produced an antianxiety agent effect.

This exciting finding was reported in nature article in 2011 under the title "Amygdala circuitry mediating reversible and bidirectional control of anxiety". However it is fair to say that the field of optogenetics is still in its early stages, where much development could be done, on light sources, transfection methods and electrodes design.