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Mice Choose Best Escape Route Without Ever Experiencing Threat

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Summary: After only ten minutes in a novel environment, mice are able to learn the shortest escape route even if they have no experience of a threat in the location.

Source: Sainsbury Wellcome Center

Escaping imminent danger is essential for survival. Animals must learn a new environment fast enough for them to be able to choose the shortest route to safety. But how do they do this without ever having experienced threat in the new environment?

Neuroscientists at the Sainsbury Wellcome Centre at UCL explored how mice learn about their spatial environment and the behavioral strategies they use to take the shortest route to a shelter when they are scared.

In a new study, published today in Current Biology, the researchers show that mice learn the shortest route to escape after only 10 minutes of exploring the environment and they do not need previous experience of threat.

“In many neuroscience studies, mice are trained to solve complex mazes and are given lots of time to learn how to do so. But in nature, mice do not have that luxury – when faced with threat, they must escape to shelter as quickly as possible. The question is how do mice learn this very quickly, without the opportunity of trial and error,” said Tiago Branco, Group Leader at the Sainsbury Wellcome Centre and corresponding author on the paper.

To explore this question, the SWC researchers carried out a series of behavioral experiments where they gave mice a choice of two or three routes back to a shelter. The scientists used a loud sound or looming stimulus, simulating a predator, to scare the mice and then observed their route back to shelter.

Firstly, the neuroscientists blocked the direct path to shelter and found that the mice learned to use one of the other routes. Next, the researchers explored whether the mice could choose correctly between two paths of different lengths. The experiments took place in the dark, meaning that the mice could not see the shortest route.

However, the researchers observed that mice indeed prefer the shorter path, particularly when there is a larger difference between the lengths of the two paths.

To understand how the mice learn this, the researchers studied those that were experiencing threat for the first time and observed that the inexperienced mice already had a preference for the shorter route. Thus, the mice must acquire this information through natural exploration and do not have to first experience threat to learn how to choose the best escape route. Furthermore, the mice learned this after only 10 minutes of exploring the environment.

“Mice are predated on by many species and so for a mouse it’s very important to know how to escape to safety. If you put a mouse in a new environment, its priority is to map out space and figure out how to get to a safe place. This is in the natural repertoire of the mouse’s behaviour and does not have to be explicitly instructed,” said Tiago Branco.

Traditionally, the way that animals are thought to learn is to experience the value of something and map that onto the spatial geometry. For example, if mice were repeatedly exposed to threat many times and felt stressed by taking the long path back to safety, they would assign the longer path a lower value and learn to take the shorter path instead.

However, in this experiment, the animals were not doing that. Instead, the mice assumed that the short route was best for escape. The researchers refer to this assumption as an innate heuristic. Through evolution, mice have acquired a set of neural circuits that give them the ability to make these innate choices after natural exploration.

“Animals are very good at learning about the things that matter to them. To understand the mouse brain and the algorithms and neural circuits that support learning, it is important to look at the behaviours that the mouse has evolved to do and the constraints that they are under to learn fast and efficiently,” commented Tiago Branco.

To explore the algorithms the brain might be using to enable the mice to choose the best escape route, the researchers looked at three different computational models and asked whether the artificial algorithms could perform as well as the mice in the task.

They found that the three algorithms all worked very well if the artificial mouse was allowed to explore for a long time. However, the real mouse only had 10 minutes to explore.

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And so the researchers fed the artificial mouse with the trajectories that the real mouse took and they found that the simplest possible algorithm, called model-free, could not learn to choose the shortest path.

The two more complex models, called model-based, could learn the best escape route but they were only correct around half of the time. This gives the researchers some insights into what the brain needs for the mice to be able to select the optimal escape route.

The next steps for the researchers are to delve deeper into how this works in the brain and how mice map value onto actions in this natural paradigm. This question is one small piece of the larger puzzle of how animals choose what actions they are going to do based on their expectation of what is going to be best in the short-term or long-term.

The neuroscientists hope to understand this form of value mapping in an action behaviour to gain a glimpse into the kinds of algorithms the brain may be using to implement rapid learning.

Scientists Caught ‘Undead’ Genes Coming Alive After Death.

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What really happens to us after death? Once a person stops breathing, and their heart ceases to pump blood, they’re what doctors consider “clinically dead.” On a biological level, the eventual decomposition of cells, organs, and brain tissue signal its final and irreversible stages.

But what if that’s not actually the end? Two new studies claim that hundreds of genes actually kept expressing—and, in some cases, become more active—after death occurred. This came as a surprise to the researchers, because forensic pathologists have long suspected that gene activity degrades postmortem, which is why their rate of change is sometimes used to calculate time of death.

According to the lead author of both papers, microbiologist Peter Noble of the University of Washington, the discovery of “undead” genes could help to improve the preservation of organs destined for transplantation. The two studies are currently available on the pre-print server bioRxiv, and it’s important to note that neither have undergone peer review yet.

Noble says his most recent research was inspired by a three-year-old study published in Forensic Science International that discovered a host of genes that remained active in human cadavers for up to 12 hours after death.

In order to investigate the unwinding of the genetic clock, in these latest studies, the team extracted and measured messenger RNA (mRNA) levels in the tissue of recently deceased mice and zebrafish. Since mRNA plays an important role in gene expression, higher levels of this molecule should indicate more genetic activity.

In one of the studies, Noble and his colleagues were able to describe more than 1,000 genes that stayed “alive” postmortem. A total of 515 mice genes continued to operate for up to two days, while 548 zebrafish genes remained functional for an entire four days after death.

“It’s an experiment of curiosity to see what happens when you die,” Noble told Science Magazine.

One of the most surprising findings, however, was that hundreds of genes actually fired up—boosting their activity—within the first 24 hours after the animals had died. Noble suspects that many of them might have been suppressed or shut off by a network of other genes when their host was alive, and only after death were they free to “reawaken.”

The team also found that many of the genes that persisted postmortem are typically active during embryonic development, which led them to theorize that, on a cellular level, newly developing lifeforms might share a lot in common with degenerating corpses.

Other genes they identified were associated with promoting the growth of cancerous cells. These researchers believe the activation of cancer-related genes postmortem could partly explain why many transplant recipients are at higher risk of developing cancer after receiving a new organ, although this has long been attributed to the immunosuppressive drugs they’re typically prescribed. A lot more research still needs to be done.

“Since our results show that the system has not reached equilibrium yet,” one of the studies broadly speculates, “it would be interesting to address the following question: what would happen if we arrested the process of dying by providing nutrients and oxygen to tissues? It might be possible for cells to revert back to life or take some interesting path to differentiating into something new or lose differentiation altogether, such as in cancer.”

In addition to offering potentially valuable new insights into the expiration of vital transplant organs, the researchers hope their findings can also be used by forensic scientists to more accurately pinpoint time of death, which is apparently harder than it sounds.

“The headline of this study is that we can probably get a lot of information about life by studying death,” said Noble.

 

Human brain gene turns mice into fast-learners

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Scientists have spliced a key human brain gene into mice, that demonstrated accelerated learning as a result.

In the first study designed to assess how partially ‘humanising’ brains of a different species affects key cognitive functions, scientists report that mice carrying Foxp2 – a human gene associated with language – learned new ways to find food in mazes faster than normal mice.

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By isolating the effects of one gene, the research sheds light on its function and hints at the evolutionary changes that led to the unique capabilities of the human brain, the scientists say.

The findings were published in the Proceedings of the National Academy of Sciences.

“No one knows how the brain makes transitions from thinking about something consciously to doing it unconsciously,” says Ann Graybiel of the Massachusetts Institute of Technology, one of the study authors. “But mice with the human form of Foxp2 did much better.”

In a 2009 study, mice carrying human Foxp2 developed more complex neurons and more efficient brain circuits.

Building on that, Graybiel lead a team who took hundreds of mice genetically engineered to carry the human version of Foxp2, and trained them to find chocolate in a maze.

The animals had two options – use landmarks like lab equipment and furniture visible from the maze (“at the T-intersection, turn toward the chair”) or by the feel of the floor (“smooth, turn right;” “nubby, turn left”).

Mice with the human gene learned the route as well, by seven days, as regular mice did by 11, the scientists report.

Surprisingly, however, when the scientists removed all the landmarks in the room so mice could only learn by the feel-of-the-floor rule, the regular rodents did as well as the humanized ones. They also did just as well when the landmarks were present but the floor textiles were removed.

It was only when mice could use both learning techniques that those with the human brain gene excelled.

That suggested, Graybiel says, that what the human gene does is increase cognitive flexibility – it lets the brain segue from remembering consciously in what’s called declarative learning (“turn left at the petrol station”) to remembering unconsciously (take a right once the floor turns from tile to carpet).

Unconscious, or procedural, learning is the kind the feel-of-the-floor cue produced – the mice didn’t have to consciously think about the meaning of rough or smooth. They felt, they turned – much as people stop consciously thinking about directions on a regular route and navigate automatically.

If Foxp2 produces the cognitive flexibility to switch between forms of learning, that may help explain its role in speech and language.

When children learn to speak, they transition from consciously mimicking words they hear to speaking automatically. That suggests that switching from declarative to procedural memory, as the humanized mice did so well thanks to Foxp2, “is a crucial part of the process,” Graybiel says.

SCIENTISTS DISCOVER AREA OF BRAIN RESPONSIBLE FOR EXERCISE MOTIVATION

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Scientists at Seattle Children’s Research Institute have discovered an area of the brain that could control a person’s motivation to exercise and participate in other rewarding activities – potentially leading to improved treatments for depression.

Dr. Eric Turner, a principal investigator in Seattle Children’s Research Institute’s Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain – the dorsal medial habenula – controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.

Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression.

“Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression,” Turner said. “But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain’s activity.”

Dr. Turner’s study, titled “Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement,” was published today by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner’s team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington’s Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner’s genetically engineered mice also lost their preference for sweetened drinking water.

“Without a functioning dorsal medial habenula, the mice became couch potatoes,” Turner said. “They were physically capable of running but appeared unmotivated to do it.”

In a second group of mice, Dr. Turner’s team activated the dorsal medial habenula using optogenetics – a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could “choose” to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.

Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula.

“Traditional methods of stimulation could not isolate this part of the brain,” Turner said. “But cutting-edge technology at Seattle Children’s Research Institute makes discoveries like this possible.”

As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients.

“Working in mental health can be frustrating,” Turner said. “We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness.”

Blood Protein Rejuvenates Aging Heart.

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A molecule found only in the blood of young mice dramatically reverses thickening and stiffening of the heart muscle in old mice.

Using proteomics in combination with a 19th-century surgical technique in which the circulatory systems of two mice are joined together, researchers have demonstrated that a protein found only in the blood of young mice reverses the effects of aging in old mice, according to a study published this week (May 9) in Cell.

“I think it’s a stunning result that, for the first time, points at a secreted protein that maintains the heart in a young state,” cardiologist Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease in San Francisco, who was not involved with the research, told Nature. “That’s pretty remarkable.”

Heart failure in elderly people is often caused by cardiac hypertrophy, a thickening of the heart muscle that results in the shrinking of the chambers within. To understand what causes this age-related thickening, and to search for a way to reverse it, stem cell biologists from Harvard University tested the effect of circulating factors in young blood on aging hearts.

To do so, they turned to a centuries-old technique called heterochronic parabiosis, in which two live animals of different ages are surgically joined together to share blood circulation. Having surgically linked the blood supply of five 2-year-old mice with five 2-month-old mice, the researchers found that, after 4 weeks of exposure to young blood, the older mice’s heart muscles had dramatically thinned and softened.

Using protein-analysis techniques to narrow down the list of what could be responsible for this reversal, the researchers identified a molecule called growth differentiation factor 11 (GDF-11), a circulating factor in young mice that declines with age. The team then showed old mice treated with GDF-11 for 30 days experienced that same heart rejuvenation as those in the parabiosis experiment, demonstrating that the molecule—which also appears in human blood—may hold promise for treating cardiac aging.

“It’s conceivable that this is just an interesting mouse story,” Richard Lee of the Harvard Stem Cell Institute told ScienceNOW, “but we’re hoping to get data that might tell us that it pertains to humans.”

Source: http://www.the-scientist.com