Enlarge /. 11 September 2019, Brandenburg, Niederfinow: A house mouse (Mus musculus) sits on a biologist's glove.
Hibernating animals experience a variety of amazing changes. The metabolism drops and is completely rewired so that it works without food. Body temperatures and activity decrease. Despite all these changes, the animals remain somewhat functional – bears manage to give birth to their cubs while they are hibernating.
We have very little idea how all of these transformations take place. This week, two different research groups published articles describing the neurons that control a similar state known as congealing in mice. While mice do not hibernate, these results suggest an obvious target in mammals that hibernate. And there is a prospect that hibernation-like conditions could be available to all mammals, including us.
While mice do not go into hibernation like some other species, they have a similar condition called stiffness. Solidification can be triggered by a combination of low temperatures and lack of food. There is a significant overlap between hibernation and hibernation because the body temperature and activity of mice decrease, as does breathing and heart rate. In contrast to hibernation, the phases of solidification are relatively short, and the mice mix in phases of aggressive foraging.
Despite these differences, mice are great for studying the process, and not just because they are easier to work with than bears. In decades of research, we have developed a variety of tools that allow us to understand the genetics and physiology of mice in a detail that is simply not possible with other species. These tools enabled the two groups to identify the neurons that control entry into solidification.
The first team to work in Boston started by inducing stiffness in mice and then staining their brain in areas of high neuronal activity. The researchers next compared them to the areas that were illuminated in mice that did not solidify. Mice obviously don't have a lack of things in their brains, regardless of whether they freeze – they're cold and hungry after all – and freezing is likely to take a lot of brain activity to do. Therefore, researchers had to rely on a combination of Allen Brain Atlas and machine learning to identify the specific regions that differed between torpored mice and controls. Even then, they ended up with 190 different regions.
Which are critical?
To find out which of these 190 were critical, the researchers injected a manipulated virus that contained a gene that they could use to activate neurons with a drug. This would only infect cells near where the virus was injected. By injecting them into different locations in a large collection of mice, the researchers created a series of partially overlapping brain areas that could be activated at will. By determining which of these mice would become paralyzed in response to the drug, they could narrow the locations that cause paralysis.
They developed a region called the anterior hypothalamus, which had already been linked to body temperature and energy control. The activation of specific neurons in this region caused a dramatic drop in mouse activity and body temperature. The inactivation disrupted the mouse's ability to enter the solidification even when it was kept hungry and cold.
Follow the genes
The second research group based in Japan did things very differently. These researchers started with a protein that we didn't even know existed until computer algorithms found it in the genome sequence. Early studies linked it to food intake and anxiety, but the researchers were curious to learn more. So they identified cells in the brain that produced the protein and began examining them.
The researchers designed mice so that all the cells that produced the protein would also produce the same drug-activated gene that the Boston research team had used. This enabled them to activate the same neurons. Thirty minutes after receiving the drug, the mice reduced their activity dramatically, just as if they went into solidification. As in the previous study, there were a number of cells that made the protein, so the researchers had to inject a little to identify the specific cells involved.
This team spent some time characterizing the state of solidification that could be induced by these cells. Mice usually have a body temperature above 40 ° C. When the cells are activated, they fall below 30 ° C for 48 hours. Heart rate drops dramatically and oxygen consumption also decreases. In fact, breathing became so shallow that the researchers could not see it with the instruments they had.
Although it wasn't hibernation, it looked very similar.
Hibernation is actually widespread in mammals that are not necessarily closely related in evolutionary terms. This suggests that the differences between numbness and true hibernation are more a question of degree than differences in the process that triggers it. It also suggests that animals that don't show up either – a group we belong to – could go through a torporal process if these neurons are activated.
Nature, 2020. DOI: 10.1038 / s41586-020-2387-5 and 10.1038 / s41586-020-2163-6 (About DOIs).