Awaken the beast in me: optogenetics turned mice into predators

Scientists have been able to turn on neurons that make mice behave aggressively

Unlike rats, mice appear to us as peaceful creatures that feed on seeds, love cheese and can gnaw on soap in our country house. But what many see as the unshakable foundations of the world order can be changed. “Bearded” joke “Don’t wake the beast in me. – And we are not afraid of hamsters! takes on a new sound. Scientists from Yale University have demonstrated that a rodent, whose jaws are used to eat grains, can be turned into a formidable consumer of the second order, killing prey with one bite, if you turn on his “predatory instinct.” The meaning of the research paper published in the journal Cell  , of course, not in creating an army of bloodthirsty mice or shaking the foundations of the universe by swapping the places of predators and prey. In fact, through this experiment, a network of neurons was identified that is responsible for chasing prey.

Werewolf mice

If you look for videos where a mouse is eating someone, you can probably stumble upon the opposite situation: the mice themselves are eaten by tarantulas, millipedes, and even chickens. Now imagine ordinary mice that walk around the cage and do not give themselves away. But as soon as you turn on the laser, they all turn into “zombies”, which, like in the TV series “The Walking Dead”, begin to chase and bite everything in their path, even sticks and bottle caps.

“We turned on the laser, and they began to jump on objects, grab them with their paws and bite vigorously, as if they were trying to grab and kill prey,” – this is how the head of the research group Ivan de Arujo describes the mouse metamorphoses , an assistant professor of psychiatry at the Yale University School of Medicine from the laboratory named after John Pierce.  

What is the mechanism that made laboratory mice forget about their usual behavioral patterns and start attacking everything? Like werewolves from horror stories under the beam of the full moon, these rodents begin to show predatory habits under the influence of light. But do not rush to break the light bulb in the basement, because ordinary mice will not turn into ferocious and ruthless killers just like that.

The only known exception – the giant descendants of mice, accidentally brought by ships from Gough Island (Tristan da Cunha Archipelago, Atlantic Ocean), which feed on the chicks of the endemic songbird, the Gough Rovettian Bunting , and large sea albatrosses and petrels – only confirms the rule. The rodents that bred in the absence of natural enemies were forced to find a new source of food, and what else can you profit from on the island, where huge numbers of seabirds nest? But even these mice do not kill chicks (whose parents, by the way, can weigh as much as 300 times more predators), but simply bite off pieces of them, eating them alive (although, of course, it sounds and looks no less creepy, and the damage to the population of majestic rodents cause a lot of birds).   

Optogenetics : “bulbs in the head”

Optogenetics , a new method of controlling impulses inside a living organism with the help of light , helped to find brain regions that include the hunting instincts of animals . The possibilities of this approach are impressive: electrochemical impulses are the communication between neurons, so by controlling them, you can interfere with the work of the brain, erasing and changing memories and controlling emotions.

Optogenetics can also set muscles in motion (as it works, for example, in the cyborg stingray, which Indicator.Ru wrote about in his review) and help restore vision, because the proteins on the action of which the method is based are special opsins (in this case, they became kanorhodopsin 2, which in nature helps Reingard’s Chlamydomonas to float into the light ), are related to those that are in our cones and sticks of eyes. The carriers of special opsins (more precisely, the genes encoding them) into the cell are vectors – harmless viruses that embed the desired piece of DNA into the DNA of the cell. Being in the membrane, they change their shape, reacting to light of a certain wavelength, and pass positively charged ions inside the cell, which changes the ratio of charges inside and outside. As a result, a potential difference is formed and an electrochemical signal arises, which activates the chains and networks of nerve cells. 

By selectively manipulating different types of neurons, scientists have found a group that is responsible for stalking prey, and another one responsible for killing victims. The prey was not only non-living objects such as sticks, bottle caps, moving toy beetles, but also living insects (crickets).

Scientists also tried to selectively break the connections between neurons of each type and found that without the work of the ” biting ” mechanism, mice pursue prey, but cannot kill it. The bite force of their jaws in this case is reduced by 50%, and the newly minted would-be hunters are not able to commit the very deadly bite with which real predators kill prey almost instantly.

Where predator instinct dozed

Perhaps, invasive mice on Gough Island cannot overcome the same problem , which is why they practically eat albatross chicks alive. However, the chicks do not run away and cannot offer strong resistance, which, for example, is quite possible to expect from a wildebeest or a deer, whose powerful horns and hooves left no chance for a weak or sluggish predator to eat. Thus, they stimulate natural selection, which spurred wolves, lions and other hunters to learn how to kill quickly, preferably with one bite, because the second attempt may not be presented.

But in mice from the John Pierce Laboratory, if they are shined with a laser, these systems are activated, like in real predators. The systems are located in the amygdala – two groups of nuclei, or clusters of neurons, in the temporal lobes of the brain. These areas are closely related to the formation of emotions, and not only negative ones like fear and aggression, but also pleasure, and are included in the limbic system, which is responsible for the body’s adaptation to environmental conditions. Malfunctioning or damage to the tonsils is a possible cause of increased anxiety, depression, PTSD, and even autism. It is noteworthy that the amygdala is quite different in men and women, and in people of homosexual orientation, the structure of these areas is more similar to that of people of the opposite sex. Men’s amygdala is larger, and under stressful stimuli (including watching horror movies), the left is activated, triggering actions in response to emotions, while in women, the right. It’s funny that the connection of the amygdala with hunting instincts reminds of the old as the world stereotypes about the man-hunter and hunter.

Scientists are now trying to understand what information from the senses enters the amygdala in order to determine what triggers the mechanisms of predator behavior and how two groups of neurons are coordinated, one of which is responsible for the bite, and the other for the pursuit. “We have gained control over their anatomical incarnation, so we hope to be able to control them even more precisely in the future,” says de Arajo .

The Hunger Games

It is interesting that the animals did not bite their relatives, although correlations between the activity of the amygdala and the level of aggressiveness are known. “The system does not just increase aggression,” the authors of the work explain. “It seems to be related to the animal’s interest in getting food.” But hunger turned out to be associated with hunting instincts and forced the mice to actively pursue prey.

In nature, the behavior of predators often takes on complex and complex forms that are characteristic of many jaw- toots ( infratotype Gnathostomata , including the superclasses of fish and tetrapods), including humans. “This is the main evolutionary player in the formation of the brain,” notes de Arajo . “There must be a rudimentary subcortical pathway that connects the signals from the senses with jaw movement and biting .” 

The study grew out of scientists trying to understand which neural mechanisms are responsible for feeding animals. Laboratory staff watched how the mice lived in cages and how they ate. This led them to the idea of ​​studying the areas of the brain associated with hunting and feeding. There are many zones on this list, but one is responsible only for hunting, and not just food in general. This turned out to be the very central nucleus of the amygdala, which can also control the muscles of the jaws and neck involved in hunting. According to the authors of the study, this area is ideal for “switching on” the system of movements characteristic of hunting in maxillary vertebrates.

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