Cat and Mouse: A Single Gene Matters

When a mouse smells a cat, it instinctively avoids the feline or risks becoming dinner. How? A Northwestern University study involving olfactory receptors, which underlie the sense of smell, provides evidence that a single gene is necessary for the behavior.

A research team led by neurobiologist Thomas Bozza has shown that removing one olfactory receptor from mice can have a profound effect on their behavior. The gene, called TAAR4, encodes a receptor that responds to a chemical that is enriched in the urine of carnivores. While normal mice innately avoid the scent marks of predators, mice lacking the TAAR4 receptor do not.

The study, published April 28 in the journal Nature, reveals something new about our sense of smell: individual genes matter.

Unlike our sense of vision, much less is known about how sensory receptors contribute to the perception of smells. Color vision is generated by the cooperative action of three light-sensitive receptors found in sensory neurons in the eye. People with mutations in even one of these receptors experience color blindness.

“It is easy to understand how each of the three color receptors is important and maintained during evolution,” said Bozza, an author of the paper, “but the olfactory system is much more complex.”

In contrast to the three color receptors, humans have 380 olfactory receptor genes, while mice have more than 1,000. Common smells like the fragrance of coffee and perfumes typically activate many receptors.

“The general consensus in the field is that removing a single olfactory receptor gene would not have a significant effect on odor perception,” said Bozza, an assistant professor of neurobiology in the Weinberg College of Arts and Sciences.

Bozza and his colleagues tested this assumption by genetically removing a specific subset of olfactory receptors called trace amine-associated receptors, or TAARs, in mice. Mice have 15 TAARs. One is expressed in the brain and responds to amine neurotransmitters and common drugs of abuse such as amphetamine. The other 14 are found in the nose and have been coopted to detect odors.

Bozza’s group has shown that the TAARs are extremely sensitive to amines — a class of chemicals that is ubiquitous in biological systems and is enriched in decaying materials and rotting flesh. Mice and humans typically avoid amines since they have a strongly unpleasant, fishy quality.

Bozza’s team, including the paper’s lead authors, postdoctoral fellow Adam Dewan and graduate student Rodrigo Pacifico, generated mice that lack all 14 olfactory TAAR genes. These mice showed no aversion to amines. In a second experiment, the researchers removed only the TAAR4 gene. TAAR4 responds selectively to phenylethylamine (PEA), an amine that is concentrated in carnivore urine. They found that mice lacking TAAR4 fail to avoid PEA, or the smell of predator cat urine, but still avoid other amines.

“It is amazing to see such a selective effect,” Dewan said. “If you remove just one olfactory receptor in mice, you can affect behavior.”

The TAAR genes are found in all mammals studied so far, including humans. “The fact that TAARs are highly conserved means they are likely important for survival,” Bozza said.

One idea is that the TAARs may make animals very sensitive to the smell of amines. Humans may have TAAR genes to avoid rotting foods, which become enriched in amines during the decomposition process. In fact, the TAARs may relay information to a specific part of the brain that elicits innately aversive behavior in animals.

Bozza’s lab has recently shown that neurons in the nose that express the TAARs connect to with a specific region of the olfactory bulb — the part of the brain that first receives olfactory information. This suggests that the TAARs may elicit hardwired responses to amines in mice, and perhaps humans.

“We hope this work will reveal specific brain circuits that underlie instinctive behaviors in mammals,” Bozza said. “Doing so will help us understand how neural circuits contribute to behavior.”

Monkey see, monkey do

A new experimental method allows the spontaneous synchronization of arm motions by pairs of Japanese macaques to be observed under controlled conditions

Humans often synchronize their movements when, for example, we cooperate to move a piece of furniture. We also synchronize gestures and facial expressions when we interact. Coordinated actions are in fact surprisingly common in the animal kingdom, as exemplified by the flocking of birds and the schooling of fish. Such behaviors, however, have to date only been observed in the wild. Yasuo Nagasaka and colleagues from the Laboratory for Adaptive Intelligence at the RIKEN Brain Science Institute have now devised the first method for observing coordination under experimental conditions.

The researchers individually trained three Japanese macaque monkeys to press two buttons repeatedly and alternately with one hand. They then recorded the monkeys performing this task with a video camera and motion capture device.

Nagasaka and his colleagues later paired the monkeys and had them perform the task again while facing each other. Initially, each monkey in a pair pressed the buttons at different speeds. However, after a certain amount of time, the two monkeys spontaneously synchronized their button presses by altering the speed of their actions so that their button presses became harmonized with those of their partner.  

The speed of repeated button presses differed among the three pairs of monkeys, as did the timing of the synchrony. In one pair, the button presses were synchronized but one monkey was always delayed by 1 millisecond, while in another the delay was 13 milliseconds. In all cases, however, the timing of the actions became closely matched, and the delay seemed to be dependent on exactly which monkeys had been paired together. 

The researchers then played back the video recordings of the monkeys performing the task at different speeds while a monkey watched. The monkeys sped up or slowed down their button presses to harmonize their actions with those of the ‘virtual’ monkey, and they seemed to prefer to slow down their button presses, perhaps to save energy. 

In a final set of experiments, the research team allowed the real monkeys to either see or hear the video recordings, and found that visual information is far more important than auditory information for synchronization. 

“We believe that this spontaneous synchronization plays an important role in the building of social bonds, and we are now looking for the brain areas responsible,” says Nagasaka. “This could be fundamental to understanding the brain itself, and also the social interaction deficits in conditions such as autism.”

A video showing the spontaneous synchronization of monkey actions can be found here.

Bees get a buzz from caffeine

You may need a cup of coffee to kick start the day but it seems honeybees also get their buzz from drinking flower nectar containing caffeine.

Publishing in Science, researchers have shown that caffeine improves a honeybee’s memory and could help the plant recruit more bees to spread its pollen.

In tests honeybees feeding on a sugar solution containing caffeine, which occurs naturally in the nectar of coffee and citrus flowers, were three times more likely to remember a flower’s scent than those feeding on just sugar.

Study leader Dr Geraldine Wright, Reader in Neuroethology at Newcastle University, explained that the effect of caffeine benefits both the honeybee and the plant: “Remembering floral traits is difficult for bees to perform at a fast pace as they fly from flower to flower and we have found that caffeine helps the bee remember where the flowers are.

“In turn, bees that have fed on caffeine-laced nectar are laden with coffee pollen and these bees search for other coffee plants to find more nectar, leading to better pollination.

“So, caffeine in nectar is likely to improve the bee’s foraging prowess while providing the plant with a more faithful pollinator.”

In the study, researchers found that the nectar of Citrus and Coffea species often contained low doses of caffeine. They included ‘robusta’ coffee species mainly used to produce freeze-dried coffee and ‘arabica’ used for espresso and filter coffee. Grapefruit, lemons, pomelo and oranges were also sampled and all contained caffeine.

Co-author Professor Phil Stevenson from the Royal Botanic Gardens, Kew and the University of Greenwich’s Natural Resources Institute said: “Caffeine is a defence chemical in plants and tastes bitter to many insects including bees so we were surprised to find it in the nectar.  However, it occurs at a dose that’s too low for the bees to taste but high enough to affect bee behaviour.”

The effect of caffeine on the bees’ long-term memory was profound with three times as many bees remembering the floral scent 24 hours later and twice as many bees remembering the scent after three days.

Typically, the nectar in the flower of a coffee plant contains almost as much caffeine as a cup of instant coffee. Just as black coffee has a strong bitter taste to us, high concentrations of caffeine are repellent to honeybees.

Dr Wright added: “This work helps us understand the basic mechanisms of how caffeine affects our brains. What we see in bees could explain why people prefer to drink coffee when studying.”

Dr Julie Mustard, a contributor to the study from Arizona State University, explains further: “Although human and honeybee brains obviously have lots of differences, when you look at the level of cells, proteins and genes, human and bee brains function very similarly. Thus, we can use the honeybee to investigate how caffeine affects our own brains and behaviours.”

This project was funded in part by the Insect Pollinators Initiative which supports projects aimed at researching the causes and consequences of threats to insect pollinators and to inform the development of appropriate mitigation strategies.

Population declines among bees have serious consequences for natural ecosystems and agriculture since bees are essential pollinators for many crops and wild flowering species. If declines are allowed to continue there is a risk to our natural biodiversity and on some crop production.

Professor Stevenson said: “Understanding how bees choose to forage and return to some flowers over others will help inform how landscapes could be better managed. Understanding a honeybee’s habits and preferences could help find ways to reinvigorate the species to protect our farming industry and countryside.”

Homer prevents stress-induced cognitive deficits

Before examinations and in critical situations, we need to be particularly receptive and capable of learning. However, acute exam stress and stage fright causes learning blockades and reduced memory function. Scientists from the Max Planck Institute of Psychiatry in Munich have now discovered a mechanism responsible for these cognitive deficits, which functions independently of stress hormones. In animal studies, the researchers show that social stress reduces the volume of Homer-1 in the hippocampus – a region of the brain that plays a central role in learning. This specific protein deficiency leads to altered neuronal activity followed by deterioration in the animals’ learning performance. In the experiments, it was possible to prevent the cognitive deficit by administering additional volumes of the protein to the mice. This suggests that Homer-1 could provide a key molecule for the development of drugs for the treatment of stress-induced cognitive deficits.

Klaus Wagner, a scientist at the Max Planck Institute of Psychiatry, studied the learning behaviour of mice that had been subjected to severe stress. He exposed the animals to social stress – a pressure also frequently experienced by humans today. A male mouse was placed in the cage of an aggressive member of the same species for five minutes. The latter tried to banish the “intruder” by attacking it. Unlike in nature, the test mouse was unable to flee from the cage and was under severe stress, as substantiated by measurements of the stress hormones in its blood.

Following a period of eight hours in which the animal was able to recover in its own cage, its behaviour was examined. While the mouse’s motivation, activity and sensory functions were not impaired at this time, it displayed clear deficits in its learning behaviour. A single five-minute situation of social stress was sufficient, therefore, to impair the animal’s learning performance hours later.

The researchers at the Max Planck Institute then tried to establish which mechanisms were responsible for these cognitive deficits. They identified the protein Homer-1, the concentration of which declines specifically in the hippocampus after exposure to stress. Through its interaction with the neuronal messenger substance glutamate and its receptors, Homer-1 modulates the communication in the neuronal synapses. When the volume of Homer-1 in the hippocampus falls after exposure to stress, the natural receptor activity is severely disrupted and learning capacity declines. The researchers were able to prevent this effect by increasing the Homer-1 concentration again.

Mathias Schmidt, Research Group Leader at the Max Planck Institute of Psychiatry interprets the results as follows: “With our study, we demonstrated the regulation of glutamate-mediated communication in the hippocampus, which directly controls learning behaviour. This mechanism functions independently of stress hormones for the most part. The molecule Homer-1 assumes a key role in this process and will hopefully provide new possibilities in future for targeted pharmaceutical intervention for the avoidance of cognitive deficits.”

Real Angry Birds Flip ‘the Bird’ Before a Fight

Male sparrows are capable of fighting to the death. But a new study shows that they often wave their wings wildly first in an attempt to avoid a dangerous brawl.

"For birds, wing waves are like flipping the bird or saying ‘put up your dukes. I’m ready to fight,’" said Duke biologist Rindy Anderson.

Male swamp sparrows use wing waves as an aggressive signal to defend their territories and mates from intruding males, Anderson said. The findings also are a first step toward understanding how the birds use a combination of visual displays and songs to communicate with other males.

Anderson and her colleagues published the results online Jan. 28 in the journal Behavioral Ecology and Sociobiology.

Scientists had assumed the sparrows’ wing-waving behavior was a signal intended for other males, but testing the observations was difficult, Anderson said. So she and her co-author, former Duke engineering undergraduate student David Piech (‘12), built a miniature computer and some robotics, which the team then stuffed into the body cavity of a deceased bird. The result was a ‘robosparrow’ that looked just like a male swamp sparrow, which could flip its wings just like a live male.

Anderson took the wing-waving robosparrow to a swamp sparrow breeding ground in Pennsylvania and placed it in the territories of live males. The robotic bird “sang” swamp sparrow songs using a nearby sound system to let the birds know he was intruding, while Anderson and her colleagues crouched in the swampy grasses and watched the live birds’ responses. She also performed the tests with a stuffed sparrow that stayed stationary and one that twisted from side to side. These tests showed that wing waves combined with song are more potent than song on its own, and that wing waves in particular, not just any movement, evoked aggression from live birds.

The live birds responded most aggressively to the invading, wing-waving robotic sparrow, which Anderson said she expected. “What I didn’€™t expect to see was that the birds would give strikingly similar aggressive wing-wave signals to the three types of invaders,” she said. That means that if a bird wing-waved five times to the stationary stuffed bird, he would also wing-wave five times to the wing-waving robot.

Anderson had hypothesized that the defending birds would match the signals of the intruding robots, but her team’s results suggest that the males are more individualistic and consistent in the level of aggressiveness that they want to signal, she said.

"That response makes sense, in retrospect, since attacks can be devastating," Anderson said. Because of the risk, the real males may only want to signal a certain level of aggression to see if they could scare off an intruder without the conflict coming to a fight and possible death.

Uncovering maternal to paternal communications in mice

Researchers at Japan’s Kanazawa University have proven the existence of communicative signalling from female mice that induces male parental behaviour.

Most mammalian parents use communicative signals between the sexes, but it is uncertain whether such signals affect the levels of parental care in fathers. Scientists have long suspected that female mice play a definite role in encouraging paternal relationships between male mice and their pups.

Now, a research team at Kanazawa University led by Haruhiro Higashida in collaboration with scientists across Japan, Russia and the UK, have proven the existence of auditory and olfactory (smell) signals produced by females which actively trigger paternal activity in males.

Higashida and his team conducted a series of experiments with females and males living in established family groups. Pups were removed from the cage for a short time, while one or both parents remained in the nest. The pups were then returned to the cage, away from the nest. Lone females nearly always brought the pups back to the nest, but lone males were less likely to do so.

Most interestingly, the researchers showed that males were much more likely to retrieve pups when they remained with their mate. This behaviour may be related to ultra-sonic noises emitted by females under stress. These sounds are not emitted by males, pups or non-parental females, and they encouraged the males into parental behaviours. The females also released olfactory signals in the form of pheromones, which triggered the same reaction in the males.

Higashida and his team are keen to expand on their results by analyzing neural signalling in the male brain in response to these female communications.

Chimps solve puzzles for the thrill of it

Sensitive Males Provide Clues to Mind Reading in Birds

The male Eurasian jay is an accommodating fellow. When his mate has been feasting steadily on mealworm larvae, he realizes that she’d now prefer to dine on wax moth larvae, which he feeds her himself. The finding adds to a small but growing number of studies that show that some animals have something like the human ability to understand what others are thinking.

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Chimpanzees successfully play the Ultimatum Game

Researchers at the Yerkes National Primate Research Center, Emory University, are the first to show chimpanzees possess a sense of fairness that has previously been attributed as uniquely human. Working with colleagues from Georgia State University, the researchers played the Ultimatum Game with the chimpanzees to determine how sensitive the animals are to the reward distribution between two individuals if both need to agree on the outcome.

The researchers say the findings, available in an early online edition of the Proceedings of the National Academy of Sciences (PNAS) available this week, suggest a long evolutionary history of the human aversion to inequity as well as a shared preference for fair outcomes by the common ancestor of humans and apes.

According to first author Darby Proctor, PhD, “We used the Ultimatum Game because it is the gold standard to determine the human sense of fairness. In the game, one individual needs to propose a reward division to another individual and then have that individual accept the proposition before both can obtain the rewards. Humans typically offer generous portions, such as 50 percent of the reward, to their partners, and that’s exactly what we recorded in our study with chimpanzees.”

Co-author Frans de Waal, PhD, adds, “Until our study, the behavioral economics community assumed the Ultimatum Game could not be played with animals or that animals would choose only the most selfish option while playing. We’ve concluded that chimpanzees not only get very close to the human sense of fairness, but the animals may actually have exactly the same preferences as our own species.” For purposes of direct comparison, the study was also conducted separately with human children.

In the study, researchers tested six adult chimpanzees (Pan troglodytes) and 20 human children (ages 2 – 7 years) on a modified Ultimatum Game. One individual chose between two differently colored tokens that, with his or her partner’s cooperation, could be exchanged for rewards (small food rewards for chimpanzees and stickers for children). One token offered equal rewards to both players, whereas the other token favored the individual making the choice at the expense of his or her partner. The chooser then needed to hand the token to the partner, who needed to exchange it with the experimenter for food. This way, both individuals needed to be in agreement.

Both the chimpanzees and the children responded like adult humans typically do. If the partner’s cooperation was required, the chimpanzees and children split the rewards equally. However, with a passive partner, who had no chance to reject the offer, chimpanzees and children chose the selfish option.

Chimpanzees, who are highly cooperative in the wild, likely need to be sensitive to reward distributions in order to reap the benefits of cooperation. Thus, this study opens the door for further explorations into the mechanisms behind this human-like behavior.