Posts tagged rats

Posts tagged rats
Rats have a double view of the world
Scientists from the Max Planck Institute for Biological Cybernetics in Tübingen, using miniaturised high-speed cameras and high-speed behavioural tracking, discovered that rats move their eyes in opposite directions in both the horizontal and the vertical plane when running around. Each eye moves in a different direction, depending on the change in the animal’s head position. An analysis of both eyes’ field of view found that the eye movements exclude the possibility that rats fuse the visual information into a single image like humans do. Instead, the eyes move in such a way that enables the space above them to be permanently in view – presumably an adaptation to help them deal with the major threat from predatory birds that rodents face in their natural environment.
Like many mammals, rats have their eyes on the sides of their heads. This gives them a very wide visual field, useful for detection of predators. However, three-dimensional vision requires overlap of the visual fields of the two eyes. Thus, the visual system of these animals needs to meet two conflicting demands at the same time; on the one hand maximum surveillance and on the other hand detailed binocular vision.
The research team from the Max Planck Institute for Biological Cybernetics have now, for the first time, observed and characterised the eye movements of freely moving rats. They fitted minuscule cameras weighing only about one gram to the animals’ heads, which could record the lightning-fast eye movements with great precision. The scientists also used another new method to measure the position and direction of the head, enabling them to reconstruct the rats’ exact line of view at any given time.
The Max Planck scientists’ findings came as a complete surprise. Although rats process visual information from their eyes through very similar brain pathways to other mammals, their eyes evidently move in a totally different way. “Humans move their eyes in a very stereotypical way for both counteracting head movements and searching around. Both our eyes move together and always follow the same object. In rats, on the other hand, the eyes generally move in opposite directions,” explains Jason Kerr from the Max Planck Institute for Biological Cybernetics.
In a series of behavioural experiments, the neurobiologists also discovered that the eye movements largely depend on the position of the animal’s head. “When the head points downward, the eyes move back, away from the tip of the nose. When the rat lifts its head, the eyes look forward: cross-eyed, so to speak. If the animal puts its head on one side, the eye on the lower side moves up and the other eye moves down.” says Jason Kerr.
In humans, the direction in which the eyes look must be precisely aligned, otherwise an object cannot be fixated. A deviation measuring less than a single degree of the field of view is enough to cause double vision. In rats, the opposing eye movements between left and right eye mean that the line of vision varies by as much as 40 degrees in the horizontal plane and up to 60 degrees in the vertical plane. The consequence of these unusual eye movements is that irrespective of vigorous head movements in all planes, the eyes movements always move in such a way to ensure that the area above the animal is always in view simultaneously by both eyes –something that does not occur in any other region of the rat’s visual field.
These unusual eye movements that rats possess appear to be the visual system’s way of adapting to the animals’ living conditions, given that they are preyed upon by numerous species of birds. Although the observed eye movements prevent the fusion of the two visual fields, the scientists postulate that permanent visibility in the direction of potential airborne attackers dramatically increases the animals’ chances of survival.
When animals are on the hunt for food they likely use many senses, and scientists have wondered how the different senses work together.

New research from the laboratory of CSHL neuroscientist and Assistant Professor Adam Kepecs shows that when rats actively use the senses of smell (sniffing) and touch (through their whiskers) those two processes are locked in synchronicity. The team’s paper, published today in the Journal of Neuroscience, shows that sniffing and “whisking” movements are synchronized even when they are running at different frequencies.
Studies in the 1960s suggested these two sensory activities were coordinated: sniffing, a sharp, profound intake of air; and whisking, the back-and-forth movement of the whiskers to sample the near environment, akin to the sensation of touch as felt through the fingers in humans. Such coordination could be important for decisions that depend on multiple types of sensory information, for instance, locating food. “The question is how two very different streams of sensory information, touch and smell, are integrated into a single multisensory “snapshot” of the environment,” says Kepecs.
These snapshots can be taken at high frequency, up to 12 times a second. To determine whether these two sensorimotor rhythms are indeed phase-locked, Kepecs’ team, including postdocs Sachin Ranade and Balázs Hangya, simultaneously monitored sniffing and whisking in rats freely foraging for food pellets.
At different frequencies occurring between 4-12 times per second they found strong 1:1 phase locking — in other words, every time the rats extended their whiskers to feel their vicinity, they also smelled it. Surprisingly, they found even when the sniffing and whisking rhythms operating at different fundamental frequencies they were locked in phase. Key to this is that the phases of the sensory input – the start of inhalation and onset of whisking – are aligned, which facilitates multisensory integration.
This is similar to how a person’s breathing rhythm settles into place while running and is synchronized to the steps. In both cases, the coordination could be advantageous in terms of energy efficiency. A crucial difference, though, is that in humans, the breathing rate has to catch up to the running rhythm after changes in pace, while for sniffing and whisking in rats they lock into phase immediately.
Even though human behavior doesn’t seem to be overtly tied to rhythms, there are hints that it could be. “Underneath the smoothly executed movements of humans there are rhythm generators, which are sometimes revealed in some diseases, for example the tremors seen in Parkinson’s disease, or in the brain waves that result from the synchronized firing of neurons,” says Kepecs. Studying the rhythms of multisensory inputs in rodents could provide clues to a fundamental principle underlying sensory and brain rhythms that are essential to all animals, including humans.
(Source: cshl.edu)

Longer Days Bring ‘Winter Blues’—For Rats, Not Humans
Most of us are familiar with the “winter blues,” the depression-like symptoms known as “seasonal affective disorder,” or SAD, that occurs when the shorter days of winter limit our exposure to natural light and make us more lethargic, irritable and anxious. But for rats it’s just the opposite.
Biologists at UC San Diego have found that rats experience more anxiety and depression when the days grow longer. More importantly, they discovered that the rat’s brain cells adopt a new chemical code when subjected to large changes in the day and night cycle, flipping a switch to allow an entirely different neurotransmitter to stimulate the same part of the brain.
Their surprising discovery, detailed in the April 26 issue of Science, demonstrates that the adult mammalian brain is much more malleable than was once thought by neurobiologists. Because rat brains are very similar to human brains, their finding also provides a greater insight into the behavioral changes in our brain linked to light reception. And it opens the door for new ways to treat brain disorders such as Parkinson’s, caused by the death of dopamine-generating cells in the brain.
The neuroscientists discovered that rats exposed for one week to 19 hours of darkness and five hours of light every day had more nerve cells making dopamine, which made them less stressed and anxious when measured using standardized behavioral tests. Meanwhile, rats exposed for a week with the reverse—19 hours of light and five hours of darkness—had more neurons synthesizing the neurotransmitter somatostatin, making them more stressed and anxious.
“We’re diurnal and rats are nocturnal,” said Nicholas Spitzer, a professor of biology at UC San Diego and director of the Kavli Institute for Brain and Mind. “So for a rat, it’s the longer days that produce stress, while for us it’s the longer nights that create stress.”
Because rats explore and search for food at night, while humans evolved as creatures who hunt and forage during the daylight hours, such differences in brain chemistry and behavior make sense. Evolutionary changes presumably favored humans who were more active gatherers of food during the longer days of summer and saved their energy during the shorter days of winter.
“Light is what wakes us up and if we feel depressed we go for a walk outside,” said Davide Dulcis, a research scientist in Spitzer’s laboratory and the first author of the study. “When it’s spring, I feel more motivation to do the things I like to do because the days are longer. But for the rat, it’s just the opposite. Because rats are nocturnal, they’re less stressed at night, which is good because that’s when they can spend more time foraging or eating.”
But how did our brains change when humans evolved millions of years ago from small nocturnal rodents to diurnal creatures to accommodate those behavioral changes?
“We think that somewhere in the brain there’s been a change,” said Spitzer. “Sometime in the evolution from rat to human there’s been an evolutionary adjustment of circuitry to allow switching of neurotransmitters in the opposite direction in response to the same exposure to a balance of light and dark.”
A study published earlier this month in the American Journal of Preventive Medicine found some correlation to the light-dark cycle in rats and stress in humans, at least when it comes to people searching on the internet for information in the winter versus the summer about mental illness. Using Google’s search data from 2006 to 2010, a team of researchers led by John Ayers of San Diego State University found that mental health searches on Google were, in general, 14 percent higher in the winter in the United States and 11 percent higher in the Australian winter.
“Now that we know that day length can switch transmitters and change behavior, there may be a connection,” said Spitzer.
In their rat experiments, the UC San Diego neuroscientists found that the switch in transmitter synthesis in the rat’s brain cells from dopamine to somatostatin or back again was not due to the growth of new neurons, but to the ability of the same neurons there to produce different neurotransmitters.
Rats exposed to 19 hours of darkness every 24 hours during the week showed higher numbers of dopamine neurons within their brains and were more likely, the researchers found, to explore the open end of an elevated maze, a behavioral test showing they were less anxious. These rats were also more willing to swim, another laboratory test that showed they were less stressed.
“Because rats are nocturnal animals, they like to explore during the night and dopamine is a key part of our and their reward system,” said Spitzer. “It’s part of what allows them to be confident and reduce anxiety.”
The researchers said they don’t know precisely how this neurotransmitter switch works. Nor do they know what proportion of light and darkness or stress triggers this switch in brain chemistry. “Is it 50-50? Or 80 percent light versus dark and 20 percent stress? We don’t know,” added Spitzer. “If we just stressed the animal and didn’t change their photoperiod, would that lead to changes in transmitter identity? We don’t know, but those are all doable experiments.”
But as they learn more about this trigger mechanism, they said one promising avenue for human application might be to use this neurotransmitter switch to deliver dopamine effectively to parts of the brain that no longer receive dopamine in Parkinson’s patients.
“We could switch to a parallel pathway to put dopamine where it’s needed with fewer side effects than pharmacological agents,” said Dulcis.
With their whiskers rats can detect the texture of objects in the same way as humans do using their fingertips. A study, in which some scientists of SISSA have taken part, shows that it is possible to understand what specific object has been touched by a rat by observing the activation of brain neurons. A further step towards understanding how the brain, also in humans, represents the outside world.
We know the world through the sensory representations within our brain. Such “reconstruction” is performed through the electrical activation of neural cells, the code that contains the information that is constantly processed by the brain. If we wish to understand what are the rules followed by the representation of the world inside the brain we have to comprehend how electrical activation is linked to the sensory experience. For this reason, a team of researchers including Mathew Diamond, Houman Safaai and Moritz von Heimendahl of the International School for Advanced Studies (SISSA) of Trieste have analyzed the behavior and the activation of neural networks in rats while they were carrying out tactile object recognition tests.
During the experiments researchers observed the performance of rats – the animals were discriminating one texture from another – along with the activation of a group of sensory neurons. “For the first time the study has monitored the activity of multiple neurons, while until now, due to technical limitations, researchers had examined only individual neurons,” explains Diamond, who heads up the Tactile Perception and Learning Lab at SISSA. “The activity of such groups of neurons is represented in our model as multi-dimensional clouds, comprising as many dimensions as the number of cells under examination (up to ten). We have observed a different cloud for the contact with each different texture.”
By analyzing the “clouds”, Diamond and his colleagues were able to successfully decode the object contacted by the rodent. “Our method is so accurate that when the rat would mistake one object for another, the decoding would also indicate a different object from the one actually touched. And this happened because the representation made by the brain – and, as a consequence, our decoding – appeared like that of a different object. Hence the error.”
Diamond’s team has no intention of stopping here. “In real life, we generally recognize objects using more senses all together, in an integrated manner. We use touch and sight at the same time, for instance,” explains Diamond. “For this reason we are now working on new experiments employing more neurons, with more complicated stimuli, and more senses, to build ‘multimodal’ representations of objects.”
More in detail…
This kind of “mind reading” carried out on rats’ brain by Diamond and his colleagues is important to understand how the brain forms a representation of the world. “Each one of us perceives a physical world outside ourselves, yet actually all we have at our disposal to create an experience of the world is the representation that our brain makes of it through the input of sensory organs” says Diamond.
To understand that such a representation is at the very least partial it is enough to think of all the information about the world that escapes us all the time: for instance, we are blind to infrared and ultraviolet rays, we are unable to hear certain sound frequencies or smell some chemical substances or others. Some details pertaining to the physical world are completely invisible or, to put it better, imperceptible (others are interpreted incorrectly, like visual illusions, for example.)
This is a further demonstration that what we perceive is not the physical world in itself, but the neuronal activation the world evokes inside our brain.
The motivation to move: Study finds rats calculate ‘average’ of reward across several tests
Suppose you had $1,000 to invest in the stock market. How would you decide to pick one stock over another? Scientists have made great progress in understanding the neuroscience behind how people choose between similar options.
But what happens when neither choice is right?
During an economic downturn, for instance, your best option might be not to invest at all, but to wait for market conditions to improve.
Using an unusual decision-making study, Harvard researchers exploring the question of motivation found that rats will perform a task faster or slower depending on the size of the benefit they receive, suggesting that they maintain a long-term estimate of whether it’s worth it to them to invest energy in a task.
As described in an April 14 paper in Nature Neuroscience, a research team led by Naoshige Uchida, associate professor of molecular and cellular biology, found that rats averaged how much benefit they received over as many as five trials. When their brains were impaired in one region, however, the rats based their actions solely on the prior trial.
“This is a new framework to think about decision-making,” Uchida said. “There have been many studies that focused on action selection or choices, but the question of the overall pace or rate of performance has been largely ignored.”
To get at those decision-making questions, Uchida and his team designed the experiment.
In each trial, rats were presented with an apparatus that had three holes. Based on whether a sweet or sour odor was delivered through the middle hole, rats went either left or right to receive a water reward. On one side they received a large reward; the other side delivered a smaller reward.
“What we measured was, after getting the reward, how quickly they went back to initiate the next trial,” Uchida said.
What researchers found, Uchida said, was surprising. When rats received, on average, a larger reward, they were more likely to quickly initiate the next trial, which suggested that they weren’t reacting merely to the prior result, but were “averaging the size of the reward from several previous trials.”
“They essentially calculate the average over the previous five or six trials, and adjust their performance accordingly,” Uchida said. “They’re making a calculation to determine whether they’re getting something out of the task or not. If it’s worth it for them, they go faster. If not, they go slower.”
When researchers impaired part of the striatum, a brain structure that is part of the basal ganglia and is thought to be involved with associative thinking, in the rats’ brains, however, that calculation changed. Rather than considering the average of multiple trials, the rats chose whether to go slower or faster based solely on the prior result.
“They still go faster or slower depending on the size of the reward, but they base that decision only on the size of the reward they just got,” Uchida said. “So the rat becomes very myopic. They only care about what just happened, and they don’t take other trials into account.”
In addition to shedding new light on how decision-making happens, the study may also offer some hope for people suffering from Parkinson’s disease.
“This part of the striatum receives a great deal of inputs from dopamine neurons, so it may be related to Parkinson’s disease,” Uchida said. “Some people now think Parkinson’s may actually be related to the motivation, or ‘vigor’ to perform some movement. So if we can identify brain regions that are involved in the regulation of general motivation, it’s possible that it could be contributing to the symptoms of Parkinson’s disease.”
Going forward, Uchida said, he hopes to study the role dopamine plays in regulating motivation and decision making, as well as working to understand what role other areas of the striatum might play in the process.
“There are some interesting similarities between this part of the striatum in rats and in humans,” he said. “One is that this area receives very heavy inputs from the prefrontal cortex. That’s an area that may be important in integrating information over a longer period of time. Deconstructing this process is a critical step to understanding our behavior, and this could go a long way toward that.”
Bat and Rat Brain Rhythms Differ When on the Move
To get a clear picture of how humans and other mammals form memories and find their way through their surroundings, neuroscientists must pay more attention to a broad range of animals rather than focus on a single model species, say two University of Maryland researchers, Katrina MacLeod and Cynthia Moss. Their new comparative study of bats and rats reports differences between the species that suggest the need to revise models of spatial navigation.
In a paper appearing in the April 19, 2013 issue of Science, the UMD researchers and two colleagues at Boston University reported significant differences between rats’ and bats’ brain rhythms when certain cells were active in a part of the brain used in memory and navigation.
These cells behaved as expected in rats, which mostly move along surfaces. But in bats, which fly, the continuous brain rhythm did not appear, said Moss, a professor in Psychology and Biology and the Institute for Systems Research.
The finding suggests that even though rats, bats, humans and other mammals share a common neural representation of space in a part of the brain that has been linked to spatial information and memory, they may have different cellular mechanisms to create or interpret those maps, said MacLeod, an assistant research scientist in Biology.
“To understand brains, including ours, we really must study neural activity in a variety of animals,” MacLeod said. “Common features across multiple species tell us ‘Aha, this is important,’ but differences can occur because of variances in the animals’ ecology, behavior, or evolutionary history.”
The research team focused on a brain region that contains specialized “grid cells,” so named because they form a hexagonal grid of activity related to the animal’s location as it navigates through space. This brain region, the medial entorhinal cortex, sits next to the hippocampus, the place that, in humans, forms memories of events such as where a car is parked. The medial entorhinal cortex acts as a hub of neural networks for memory and navigation.
Grid cells were first noticed in rats navigating their environment, but recent work by Nachum Ulanovsky (Moss’s former postdoctoral researcher at UMD) and his research team at the Weizmann Institute in Rehovot, Israel, has shown these cells exist in bats as well.
In rats, grid cells fire in a pattern called a theta wave when the animals spatially navigate. Theta waves are fairly low-frequency electrical oscillations that also have been observed at the cellular level in the medial entorhinal cortex. The prominence of theta waves in rats suggested they were important. As a result, neuroscientists, trying to understand the relationship between theta waves and grid cells, have developed models of the brain based on the assumption that theta waves are key to spatial navigation in mammals.
However, Moss said, “recordings from the brains of bats navigating in space contain a surprise, because the expected theta rhythms aren’t continuously present as they are in the rodent.”
The new Science study doubles down on the lack of theta in bats by reporting that theta rhythms also are not present at the cellular level. “The bat neurons don’t ‘ring’ the way the rat neurons do,” says MacLeod. “This raises a lots of questions as to whether theta rhythms are actually doing what the spatial navigation theory proposes in rats or even humans.”
Research has implications for understanding memory and imagination
While studying rats’ ability to navigate familiar territory, Johns Hopkins scientists found that one particular brain structure uses remembered spatial information to imagine routes the rats then follow. Their discovery has implications for understanding why damage to that structure, called the hippocampus, disrupts specific types of memory and learning in people with Alzheimer’s disease and age-related cognitive decline. And because these mental trajectories guide the rats’ behavior, the research model the scientists developed may be useful in future studies on higher-level tasks, such as decision-making.
The details of their work were published online in the journal Nature on April 17.

“For the first time, we believe we have evidence that before a rat returns to an important place, it actually plans out its path,” says David Foster, Ph.D., assistant professor of neuroscience at the Johns Hopkins University School of Medicine. “The rat finds that location in its mind’s eye and knows how to get there.”
Foster and his team found that, at least for the purposes of navigation, the “mind’s eye” is located in the hippocampus, which is composed of two banana-shaped segments under the cerebral cortex on both sides of the brain. It is best known for creating memories. In people with Alzheimer’s, it is one of the first parts of the brain to sustain damage.
The Foster lab experiments focused on a group of neurons in the hippocampus called place cells because they are known to fire when animals are at a given location within a given environment. What was not known, Foster says, was how and when the brain uses that information.
By miniaturizing an existing technology, Foster and a postdoc in his lab, Brad Pfeiffer, Ph.D., were able to implant 20 microwires into each side of the hippocampus of four rats. The tiny wires let them record electrical activity from as many as 250 individual place cells at the same time, more than ever achieved before.
Over a two-week training period, the rats became familiar with the testing area which was surrounded by a variety of objects, so that the rats could tell where they were in relation to the objects outside. The space was 2 meters square with 36 tiny “dishes” placed at regular intervals in a grid. A single dish at a time would be filled with the rats’ reward: liquid chocolate.
The rats’ navigation tests involved as many as 40 sets of alternating “odd” and “even” trials per day. The odd trials required the rats to “forage” through the arena to find a chocolate-filled dish in a random location; the even trials required the rats to return each time to a “home” dish to receive their reward. While the rats fulfilled their tasks, the researchers recorded the firing of their place cells.
They found that as a rat travels randomly through the box without knowing where it needs to go, different combinations of place cells fire at each location along its path. The same set of cells fires every time the rat travels the same spot. These unique combinations of firings “mark” each spot in the rat’s brain and can be reconstructed into what seems like a virtual map, when needed.
When a rat is about to go to a specific location, e.g., “home,” place cells in its hippocampus fire in a sequence that creates a predictive path, which the rat then follows, somewhat like Hansel and Gretel following an imagined bread crumb trail.
Foster says that “unlike a Hansel and Gretel bread crumb trail, which only allows you to leave by the same route by which you entered, the rats’ memories of their surroundings are flexible and can be reconstructed in a way that allows them to ‘picture’ how to quickly get from point A to point B.” In order to do this, he says, the rats must already be familiar with the terrain between point A and point B, but, like a GPS, they don’t have to have previously started at point A with the goal of reaching point B.
Foster says the elderly can get lost easily, and research on aged mice shows that their place cells can fail to distinguish between different environments. His team’s research suggests that defective place cells would also affect a person’s ability to “look ahead” in their imaginations to predict a way home. Similarly, he says, higher-order brain functions, like problem solving, also require people to “look ahead” and imagine themselves in a different scenario.
“The hippocampus seems to be directing the movement of the rats, making decisions for them in real time,” says Foster. “Our model allows us to see this happening in a way that’s not been possible before. Our next question is, what will these place cells do when we put obstacles in the rats’ paths?”