Remote controlled rodents

05 February 2019

Interview with

Kay Maxine Tye, MIT

RODENT

A rat grooming

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The technique called “optogenetics” involves adding a light-sensing gene to nerve cells. This makes the nerve cells become light-sensitive themselves, enabling scientists to switch on and off different brain areas by implanting a small light-source into the brain. Georgia Mills spoke to Kay Maxine Tye, who uses optogenetics at MIT to understand how the different parts of the nervous system contribute to brain function and the generation of complex behaviours. She first of all explained how you make nerve cells light-sensitive...

Kay - The first projects well that became really popular was channelrhodopsin and channelrhodopsin is an algal protein so it's found an algae pond scum. And somehow this single-celled organism 'knows' that it needs to swim towards light where, actually, how it does this is that there is a light-sensitive channel and when that light hits that channel it opens. That, in the case of an algae, makes a little flagellum flap so that the algae moves forward. In neurons, it would make the neuron fire an action potential which is the means by which neurons can communicate with each other.

Georgia - Right. So by putting this protein; making sure it's expressed in certain parts of the brain when light is present you can basically switch them on.

Kay - Exactly.

Georgia - How do you get the protein to express only in the neurons you're interested in? 

Kay - A common way is to use a viral vector. There are all different types of viruses and you can express any gene of interest in a virus. The virus infects the cell and then the cell starts producing whatever that gene codes for. So in the case of channelrhodopsin I can package it into a virus and then use the virus to infect certain cells. Based on the cell type we can control the expression of channelrhodopsin.

Georgia - So what kinds of things are people using optogenetics for?

Kay - It's a really powerful tool because it allows us to go in and, you know the brain is just this big grey ball of mush, and how do we know how it works? We can piece by piece test what happens to the rest of the brain as well as to the animal's behaviour when we manipulate the activity of select populations of neurons. We can define those populations of neurons by what they produce, what type of neuron they are, what their connections are, and that helps us sort of dissect the circuitry of the brain.

Georgia - Could you give me a couple of examples of what you've actually made animals do?

Kay - Yes. So in our group, we publish a paper in 2015 and found that if you activate GABAergic, these are inhibitory neurons that project from the lateral hypothalamus to the ventral tegmental area, which is where most dopamine neurons are found... If you activate these GABAergic neurons what you get is - you know, we place the animal in an empty chamber and you start stimulating these neurons and the animal will begin licking the floor and then it will shift its way and engage as if it's picking up food from the ground and eating it, except that there's no food it's an empty cage. So their paws are empty, yet they're sitting back holding it up to their face and engaging in what looks like feeding behaviour. Another result that we've seen is you stimulate certain populations of neurons, for example, in the brain stem and you'll get all sorts of really robust escape-related behaviour: animals leaping out of their cage, jumping off of apparatus. One of my students once called this the popcorn mouse we got popcorn mice because the mice are just leaping all over, and that suggests that we're tapping into an escape related circuit.

Georgia - It sounds like this is quite a young field but there's amazing things being done already. How far do you think this could go? Could we get to the stage where we have like remote controlled mice?

Kay - I don't think remote controlled mice is very far off at all, I mean, wireless stimulation devices exist. I mean, the hardest part would be like the battery life of the wireless control. I mean, that we basically have now. I think that if that doesn't exist now it's, you know, a few months away from making possible.

Georgia - Wow. So you're telling me you could get a mouse and sort of say: "forward, left, right". That kind of thing?

Kay - Yeah, yeah! I mean, we can control motor cortex, we can make mice run in a circle. If we had two different lights on the different sides you could make the mice run left or right, or forward or freeze. I think running backwards is a little bit trickier. I mean, to me, a remote control mouse feels very much within reach.

Georgia - Do you think it could ever be done in humans?

Kay - I think the biggest concern that I would have about using it in the brain for humans - although I believe optogenetics is already being used for retinal prosthetics for people who are blind and to help them see, and for bladder control. Things are on the periphery of cases in which function is already completely lost and so there's relatively little to risk. But I think in terms of using it in the brain we still are just beginning to understand brain function. And so I think that is still quite dangerous because the viral tools that we have for expressing these transgenes which will be the only way to get into a human would be potentially feasible if, and only if, they could become stable and safe. And I think that is a big 'if'. Currently all the viral vector tools that I'm aware of and familiar with and have used have some level of toxicity.

Georgia - All right. So you don't have to worry about being remote controlled humans just this minute?

Kay - No! I think there's all sorts of ethical concerns that I hope will prevent irresponsible exploration!

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