Optogenetics: The ultimate ‘light bulb’ moment

If the system underlying the ‘mind’ is a network of neurons constantly firing and wiring, then surely ‘mind control’ could be achieved by controlling the activity of neurons? Imagine being able to switch groups of neurons on and off instantaneously as simply as flipping a light switch. In fact, why not use light itself to control neurons; to control minds? How would you turn neurons deep in the dark depths of your brain into light-responders?……….Welcome to optogenetics (‘opto’ comes from ‘optos’, Greek for ‘visible’).

Science has yet again used a once thought ‘lower’ organism to make massive steps in understanding the way our biology works. The simple algae Chlamydomonas reinhardtii looks pretty unremarkable – it swims about generally doing what algae do: photosynthesise, swim, repeat, etc. What makes it interesting, however, is that it can detect which way to swim using its ‘eyespot’. This eyespot, found on the surface of the alga, contains a pore called channel rhod-opsin that opens in response to light (in particular, blue light). When this channel is open, it lets calcium into the cell. In this case, calcium acts like the alga’s engine ignition. The calcium ions activate propeller-like flagellae, which do a sort of tiny breast-stroke towards the source of light.

As well as being an unexpectedly neat way of guiding this humble green blob towards the sun’s rays, this system is also a massively useful experimental tool. Until recently when scientists wanted to activate neurons they tended to rely on either drugs or electrical stimulation. These methods are far from perfect since drugs can be slow and may cause unwanted side effects; whilst electrical stimulation is too imprecise to target very specific groups of cells. Algae have now inspired scientists into designing similar light-responsive systems that they can whack into groups of neurons. With a bit of tinkering these systems can be targeted to any number of different neuron types and can respond to a variety of different coloured light. Some systems are slight tweaks on the basic channel rhod-opsin unit whilst others combine opsins from other types of algae or microbes that react to different coloured lights or for different lengths of time. Whatever the mechanism, these are tools that let you change the activity of specific groups of neurones at will – with millisecond precision.

So what can you do with these light-responsive systems – or ‘phototriggers’? Let’s start with flies. First install the DNA for a phototrigger system into neurons at the base of a fly’s wing, now from this DNA those neurons can construct their very own light-responsive receptors. These neurons become active when a light is shone on them, just like the algae. Shine a light, the neurons become active and fire, telling the wings to beat. Result: we have take-off. And just in case you’re thinking the fly just sees the light and tries to flee, the same happens in decapitated flies. Gross but true! If you want to know more or need to see it to believe it: see here.

So what else can we do with this amazing technology? Well, it has been used experimentally to help us understand a number of brain functions. For example, in order to understand how choices are made, optogenetic techniques were used to switched on and off a flies’ preference for certain smells. This led to the amazing discovery of the fly’s inner critic, an assembly of 12 neurones that govern the decisions flies make. Scientists have also inserted light-responsive elements into more complex animals in an attempt to prove a causal relationship between certain groups of brain cells and a specific behaviour. In the video below, a mouse runs around every time a blue light is shone into its brain, meaning that the switching on of the light-activated brain cells causes the mouse to run. Another study made a mouse ‘prefer’ to freeze on the spot by illuminating – and therefore activating – its reward centres every time it chanced upon a particular place in its cage. These experiments are elegant and powerful because they identify the particular set of brain cells that cause, or lead to some pretty complex actions. More recently, in a bid to unravel the mysteries of how the brain deals with fear and rewards, scientists have used a similar light sensitive system to make rats remember a fearful situation. If mice or rats have minds (the complexities of which, we don’t know), then surely this counts as mind control?

 

When I first heard about optogenetics, I was gobsmacked at how clever and insightful the technology sounded. A small part of me was originally hesitant, however. I’ve obviously watched too many films that make me almost suspicious of a tool that could potentially enable mind control, or, dare I say it, ‘brainwashing’. Anthony Burgess’ Clockwork Orange springs to mind: “When a man cannot choose, he ceases to be a man.” (Anthony Burgess). The implications of this technology are massive and, without wanting to sound like too much of a film nerd, ‘with great power comes great responsibility’ (Spiderman, if you’re wondering). Luckily, though, after reading up on optogenetics, I’ve come round to realise that its potential for good far outweighs the fearsome idea that the technology would be used to construct an army full of mindless, Jason Bourne-esque zombies. Like I said, I watch far too many films.

Instead, the ability to manipulate the brain as we’ve never been able to in the past is being put to good use. Awful diseases like Parkinson’s, Alzheimer’s, multiple sclerosis – to name but a few – are currently not curable. In an aging population more prone to age-related brain disorders, it’s an increasingly big problem. Optogenetics is a valuable tool with which to study these diseases in order to find treatments. It may even prove a valuable tool in itself – for some Parkinson’s patients, who currently rely on drugs to switch on faulty neurones, optogenetics might offer a powerful alternative with no dodgy side effects. Not only that, but how the brain works is still, to a large extent, a mystery. Optogenetics allows scientists to essentially break the brain apart into its different components to isolate different groups of cells to study how each of them work and affect each other: ultimately leading to our ability to sense, think and act .

Post by: Natasha Bray

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