The new year has barely started and neuroscience already has new discoveries to offer. Like, did you know how to turn a mouse into a blood-thirsty maniac? How to make single neurons commit suicide? How to train Bacteria to kill? And what the hell does it all have to do with the brain? Read on for the answers!
First off, optogenetics has struck again -- in two new studies (both concerned with killing, in one way or another).
The first study1 has used light to find and manipulate the brain circuitry that orchestrates predatory hunting in mice. Now let me get it out of the way before we start: despite how good and click-baity it might sound, the scientists did not turn mice into mind-controlled killing zombies. They just prompted mice to show behavior they already show in the wild anyway: savage hunting. So how was it done? First, they injected mouse brain with a virus carrying a light-sensitive protein and made sure that only neurons they are interested in are affected by it. Now that these neurons could be influenced by light the researchers were able to activate and deactivate them by shining light on them via an optical fiber cable. The region of interest was chosen to be central amygdala -- a cluster of cells in amygdala, a structure involved in emotion and motivation, which seems to be almost primarily responsible for hunting behavior (in mice, mind you, not humans).
So when the researchers artificially activated central amygdala by shining a laser on it the mice launched predatory attacks on both live and artificial crickets as well as sticks and bottle caps (nothing is safe in the way of a hunter mouse). They intensively bit the prey and used their forepaws to kill it (or to scratch it in case of sticks and bottle caps). The fascinating story doesn’t end here. The scientists also identified that there are two cooperating separate sets of neurons in central amygdala -- one responsible for chasing the prey and another one controlling its killing. When they selectively deactivated the prey-chasing set the mice became super slow and uninterested in pursuing the prey; when the killing set was deactivated, however, the mice chased the crickets alright but failed to land the killing blow -- the biting force of their jaws was reduced by 50%. This is explained by the fact that the first set is connected to regions responsible for locomotion while the second one connects to regions telling the neck and jaw muscles to bite and kill.
So while this is not completely a Walking Dead episode the precision and opportunities opened by optogenetics are fascinating.
Blood-thirsty hunter. Courtesy of Ivan de Araujo/Cell Pres
Speaking of which, optogenetics has also been recently used to selectively eliminate single neurons from brain networks of a fruit fly2. Researchers at UC San Francisco developed an extremely precise tool called miniSOG2 which can cause single cells to become so desperate with life that they self-destruct.
The cells on the death row were genetically modified to have a tiny oxygen-producing machine (miniSOG2) in them. Then, like in the previous study, they were injected with a protein that reacts to light and activates the cell when a laser shines on it. Activation by light triggered miniSOG2 to produce oxidants which poison and damage the cell ultimately leading to its decision to destruct itself.
Neuron number two, before and after being shone on. Courtesy of Xiaokun Shu.
The researchers didn’t stop with brain cells though -- they used this tool to delete certain cells in a developing fly larva which led to specific changes in the adult fly’s wings. With this level of precision we can zoom in and study how individual cells contribute to the whole!
The next piece of news also nicely fits in the “killing” category. Salmonella, the bacteria normally causing you to spend twenty-four hours in the loo, was successfully reprogrammed into being a cancer-seeking weapon which caused brain tumors to self-destruct3. The researchers from Duke University genetically modified salmonella to attack glioblastoma, a very aggressive brain cancer, instead of your stomach. First, the bacteria was stripped of an important chemical of which glioblastomas happen to be a great source. Apart from inciting salmonella to go seek the tumor the scientists made it produce two compounds which lead cells to self-destruct. So now the bacteria would find the tumor, happily multiply in it and coincidentally produce these chemicals instigating the tumor cells (and ultimately the bacteria itself in the end) to commit suicide.
This treatment worked in 20% of the injected rats expanding their lifespan by 100 days (ca. 10 human years) and causing the tumor to go into remission. This is a great improvement as compared to the current median survival time of 15 months and the 5-year survival rate of 10%. The reason for the failure in the remaining 80% is not completely clear; however, all the rats showed initial signs of improvement right after injections. Maybe the tumor growth was too quick for bacteria to keep up, maybe one treatment was not enough, maybe something else was at work. Still, a 20% cure rate is a big deal -- even a small improvement is a big victory when fighting such an unstoppable disease.
Bacteria (pink) sneakily infiltrating tumor cells (blue). Credit: Duke University
