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Lasers activate killer instinct in mice (nature.com)
98 points by stichers on Jan 13, 2017 | hide | past | favorite | 39 comments



If anyone is wondering, the lasers aren't an essential element of what's going on here; the point is that targeted electrical stimulation to a certain area of the brain causes this behaviour. With areas on the brain surface, you could just use a wire for this.

For areas deeper in the brain, however, you can't exactly feed a wire in there without destroying things, so instead, you use optogenetics: you get a virus to be the "end" of the wire (finding the right area of the brain to live in, and then converting light pulses into electrical pulses) and then you point a laser at the brain and the viruses "go off" in response. The virus is essentially just serving as one half of an electrical optoisolator.

As an added benefit for the optogenetic approach, the electrical pulses released by the viruses are each local to their host cells, so they won't have nearly as much "bleed-over" into surrounding tissue as you'd see with one strong pulse from a wire.


This is a really nice explanation. I think it's helpful to go a little deeper and clarify that the virus itself isn't performing any electrical activity. Rather, the virus transfects the neural cells with a channel protein [0] that opens up in response to light. By opening the channel protein, the cell allows an influx of ions, which starts the electrical activity of the neuron in a very similar way to how it is 'naturally' stimulated. Furthermore, viral transfection is one of a few methods to expresses this protein in the animal. A population of mice that express it can be bred and maintained, with no need to transfect each one.

[0] https://web.stanford.edu/group/dlab/media/papers/Zhang%20Nat...


Thats pretty much right, but it's not the viruses that are interacting with the light.

The virus is injected, and then infects cells. It re-writes their DNA, like a lot of viruses we are all made sick by, and inserts a DNA code into the cell. In wild viruses, that DNA code would make other viruses and start the process of infection all over again. Here, that DNA code is for a protein called an 'opsin'. Just like in your retina and eyes, this opsin protein is affect by light of certain colors. In the case of exciting the nerve cell to 'fire' (the other general case is inhibiting the cell from 'firing') the opsin protein is in the cell wall and opens up the cell to the extra-cellular environment. Similar to osmosis, this causes some of the ions in the fluids (Sodium, Potassium, Calcium, etc) to rush in or out of the cell. The specifics depend a lot on the particular cell, but mostly on the relative concentration of the ions in the cell and in the extracellular fluids.

Shine light, the protein (delivered via viral infection) opens, ions rush in/out, the cell 'fires'.

Also, in longer axons like in the eye or the spine, you do have cross talk like with copper wires. BUT only if those axons are un-myelinated. That is bio-talk for cells that wrap around the axons of nerve cells that are very fatty in composition. Basically, myelin is like the plastic insulation you have on copper wire. They do a lot of other things too, but in the spine and eye, they act as isolators for the nerves that have to go a long distance. When that myelin 'goes wrong', you can get disorders like ALS and such.

Here are some sources to learn more about optogentics:

https://en.wikipedia.org/wiki/Optogenetics

https://www.youtube.com/watch?v=Nb07TLkJ3Ww


A couple of quibbles:

- The "invasiveness" of optogenetics is at least as bad as electrical microstimulation, in that you need to implant cannulae to inject the virus, plus some sort of fiber. It's possible to implant very thin metal electrodes that do fairly little damage; the optical stuff is currently much bigger.

- Optogenetics does have a selectivity advantage, but it's a bit different. By finding the right promotor, you can target specific cell types so that the optical protein is only expressed in (say) a specific class of interneurons, or a specific layer, or cells that project to another brain region.

- The virus itself isn't switching things on and off. Instead, the virus infects cells and causes the cells to produce a channel which light can switch on/off.


"First, they infected the mice with a virus that made the neurons in their brains sensitive to blue light."

They can do this? This is amazing to me!

It also makes me a little afraid that I'll get infected by a virus and mind controlled.


You're safe :-)

First, the virus isn't found in the wild--it's been modified to carry the gene coding for a light-sensitive protein (opsin). When the cells are infected, they start producing these proteins themselves. To do this, the virus is typically applied directly to the brain tissue.

Light causes these opsins to change shape, which then allows specific types of ions to flow through the cell (typically sodium to excite cells, chloride to suppress them). However, for this to work, the channels need to be illuminated directly, with the correct wavelength of light, so an optical fiber is implanted in or just above the brain.

If someone were to do this to you, you would have already had a pair of fairly invasive neurosurgeries, so being mind-controlled is probably the least of your worries! However, this technique only lets you activate all neurons or all neurons of a specific type within the light's path. It would be fairly hard to induce a complex behavior, unless there's a pre-existing circuit for one (as shown here, which is why this paper is so interesting) or they can find an illumination pattern to mimic one.


So what prevents a B-movie style plot of attaching these types of proteins to influenza viruses?

Is the blood/brain barrier the ultimate savior?


does the virus have to be injected too, or does it pass the blood-brain barrier?


I think that the commonly used virus is a variant of rabies, which can definitely cross the blood brain barrier.


This paper uses AAV (adeno-associated virus), which is probably the most common viral vector for optogenetics. There are several other options, including lentivirus and--yes, rabies. They all have slightly different properties in terms of their propensity to infect different cell types, payload capacity, and so on.

Rabies has the interesting ability to move trans-synaptically. Specifically, it moves "backwards" from a post-synaptic cell into its presynaptic partners. This makes it very useful for studies where you want to label or manipulate connections between areas. On the other hand, this would make it more difficult to study all cells or all cells of a specific type in one area.

Incidentally, I'm not sure if rabies crosses the blood-brain barrier per se. It moves up to the brain via peripheral nerves instead of circulating through the blood. In fact, the blood brain barrier may be a problem for rabies because it prevents immune cells from cleaning out the virus inside the central nervous system.


If you want some real nightmare fuel, imagine a fungus that gets into your body, drives you to a high place, destroys your motor control nerves so you're stuck in place, and then fatally bursts out a fruiting body from the back of your head, spreading more spores?

Be glad you're not an ant :)

https://en.wikipedia.org/wiki/Ophiocordyceps_unilateralis


Wanna go to the top of a ten-storey building?

http://www.smbc-comics.com/comic/fungus


Toxoplasmosis may have similar (if slightly more subtle) effects on humans: http://rspb.royalsocietypublishing.org/content/273/1602/2749


You'd still need for someone to cut your skull open to shine the blue light in. At that point, you've got problems either way.


"First, they infected the mice with a virus that made their amygdala sensitive to augmented optic nerve activity in response to specific pixel patterns."


Do not look back at the image of the Parrot, shatter goggles or no shatter goggles.

http://www.infinityplus.co.uk/stories/blit.htm


This is a rudimentary form of the plot of Serenity (the Firefly movie), if I'm interpreting that correctly. Kingsmen, too.


Not if you can persuade/modify a fungus to do the same thing. This is basically the plot of https://en.wikipedia.org/wiki/The_Girl_with_All_the_Gifts


Viruses are already inserted into your DNA and your physical and emotional behavior is different when exposed to sunlight compared to darkness.


Really interesting, source?


They know they are playing with fire here. You want zombie mice? because this is how you get zombie mice.

"This left him fairly certain that the experiments were triggering predation, not hunger or aggression."


They could reuse the laser to make the next-gen cat toy. Laser mice, yay!


Correct me if I'm wrong, but this sounds like the plot of "Kingsman"

Warning violent Movie ahead: https://www.youtube.com/watch?v=25683IE5v9g


I... just had a great idea for a weapon.

Anyone know the best way to get DARPA funding?


I halfway wrote a short story in my head on this about five years ago.

The science gist of it was this:

DARPA funded a project based on the ultimate goal of being able to regenerate limbs, treat PTSD, etc... Comcast got a hold of it, Comcast makes a killing handing out "vecks" for free, but sitting in the light show costs you. The light shows are orchestrated by comcast-recruited DJs to do light shows and play with your serotonin, dopamine, and adrenaline levels. People become light junkies

The kicker is that the virus has to be activated with a proprietary sequence of light.

Meanwhile, guy from failed DARPA project, the first light junky, gets this for free as a side-effect from the DARPA project, but he has to go to his friend for it.


Very vaguely similar to the novel Terminal Man by Michael Crichton.


The scientists who already had this great idea, perhaps?


Actually, why don't you sell it to some credulous enemies?


I heard about some Doctor E. Vil, who might be interested.



> Because the central amygdala is involved in so many different behaviours, she says, future research needs to tease out the precise neuronal circuits involved in hunting. “The central amygdala has been linked to escape and flight — this is completely different from that.”

In other words, don't be precise and your soldiers will run away instead of attacking the enemy.


That's awesome. Laser-activated, killer mice (along with sharks with lasers) need to be in the next Austin Powers movie.


All I ask for is sharks with frickin' laser beams attached to their heads.


Now that is a headline!


[flagged]


We detached this subthread from https://news.ycombinator.com/item?id=13392603 and marked it off-topic.


Please do not post image memes on HN.


[flagged]


If you like how this forum is different then other forums, then we shouldn't try to bring the culture from other forums here.


I enjoy the content sure, but I didn't realize a harmless gif in reaction to an admittedly scary virus that explodes insects would draw such reactions.

I'll just log off for the day and go enjoy Friday on those other forums.


Heh, I feel that same way every time I experience something like this on here. People get way too worked up over things that don't matter at all. For some reason I keep coming back here though...




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