Scientists manage to give mice ‘eating disorders’ by knocking out one gene

By Rachel Feltman

If you give a mouse an eating disorder, you might just figure out how to treat the disease in humans. In a new study published Thursday in Cell Press, researchers created mice who lacked a gene associated with disordered eating in humans. Without it, the mice showed behaviors not unlike those seen in humans with eating disorders: They tended to be obsessive compulsive and have trouble socializing, and they were less interested in eating high-fat food than the control mice. The findings could lead to novel drug treatments for some of the 24 million Americans estimated to suffer from eating disorders.

In a 2013 study, the same researchers went looking for genes that might contribute to the risk of an eating disorder. Anorexia nervosa and bulimia nervosa aren’t straightforwardly inherited — there’s definitely more to an eating disorder than your genes — but it does seem like some families might have higher risks than others. Sure enough, the study of two large families, each with several members who had eating disorders, yielded mutations in two interacting genes. In one family, the estrogen-related receptor α (ESRRA) gene was mutated. The other family had a mutation on another gene that seemed to affect how well ESRRA could do its job.

So in the latest study, they created mice that didn’t have ESRRA in the parts of the brain associated with eating disorders.

“You can’t go testing this kind of gene expression in a human,” lead author and University of Iowa neuroscientist Michael Lutter said. “But in mice, you can manipulate the expression of the gene and then look at how it changes their behavior.”

It’s not a perfect analogy to what the gene mutation might do in a human, but the similarities can allow researchers to figure out the mechanism that causes the connection between your DNA and your eating habits.

The mice without ESRRA were tested for several eating-disorder-like behaviors: The researchers tested how hard they were willing to work for high fat food when they were hungry (less, it seemed, so much so that they weighed 15 percent less than their unaltered littermates), how compulsive they were, and how they behaved socially.

In general, the ESRRA-lacking mice were twitchier: They tended to overgroom, a common sign of anxiety in mice, and they were more wary of novelty, growing anxious when researchers put marbles into their cages. They also showed an inability to adapt: When researchers taught the mice how to exit a maze and then changed where the exit was, the mice without ESRRA spent way more time checking out the area where the exit should have been before looking for where it had gone.

The social changes were even more striking: Mice will usually show more interest in a new mouse than one they’ve met before, but in tests the modified mice showed the opposite preference, socializing with a familiar mouse when a new one was also presented.

They were also universally submissive to other mice, something the researchers detected with a sort of scientific game of chicken. Two mice are placed at either end of a tube, and one always plows past the other to get to the opposite side. It’s just the way mice size each other up — someone has to be on top. But every single one of the modified mice let themselves get pushed around.

“100% of the mice lacking this gene were subordinate,” Lutter said. “I’ve never seen an experiment before that produced a 0% verses 100% result.”

The avoidance of fats has an obvious connection to human disorders. But the social anxiety and rigidity are also close analogies to disordered eating in humans.

Now that Lutter and his colleagues know that the gene does something similar in mice, they can start looking for the actual mechanism that’s tripping these switches in the brain. They know that the gene’s pathway is very important for energy metabolism, especially in the breakdown of glucose. It’s possible that mutations in the gene cause some kind of impairment in neurons’ ability to get and process energy, but they can’t be sure yet.

They’ll see if they can pinpoint affected neurons and fix them. They’re also going to test some drugs that are known to affect this gene and its pathways. It’s possible that they’ll land on a treatment that helps calm these negative behaviors in affected mice, leading to treatments for humans with the mutation.

http://www.washingtonpost.com/news/speaking-of-science/wp/2015/04/09/scientists-manage-to-give-mice-eating-disorders-by-knocking-out-one-gene/

Open Access Article here: http://www.cell.com/cell-reports/abstract/S2211-1247(15)00301-0

Scientists achieve implantation of memory into the brains of mice while they sleep

Sleeping minds: prepare to be hacked. For the first time, conscious memories have been implanted into the minds of mice while they sleep. The same technique could one day be used to alter memories in people who have undergone traumatic events.

When we sleep, our brain replays the day’s activities. The pattern of brain activity exhibited by mice when they explore a new area during the day, for example, will reappear, speeded up, while the animal sleeps. This is thought to be the brain practising an activity – an essential part of learning. People who miss out on sleep do not learn as well as those who get a good night’s rest, and when the replay process is disrupted in mice, so too is their ability to remember what they learned the previous day.

Karim Benchenane and his colleagues at the Industrial Physics and Chemistry Higher Educational Institution in Paris, France, hijacked this process to create new memories in sleeping mice. The team targeted the rodents’ place cells – neurons that fire in response to being in or thinking about a specific place. These cells are thought to help us form internal maps, and their discoverers won a Nobel prize last year.

Benchenane’s team used electrodes to monitor the activity of mice’s place cells as the animals explored an enclosed arena, and in each mouse they identified a cell that fired only in a certain arena location. Later, when the mice were sleeping, the researchers monitored the animals’ brain activity as they replayed the day’s experiences. A computer recognised when the specific place cell fired; each time it did, a separate electrode would stimulate brain areas associated with reward.

When the mice awoke, they made a beeline for the location represented by the place cell that had been linked to a rewarding feeling in their sleep. A brand new memory – linking a place with reward – had been formed.

It is the first time a conscious memory has been created in animals during sleep. In recent years, researchers have been able to form subconscious associations in sleeping minds – smokers keen to quit can learn to associate cigarettes with the smells of rotten eggs and fish in their sleep, for example.

Previous work suggested that if this kind of subconscious learning had occurred in Benchenane’s mice, they would have explored the arena in a random manner, perhaps stopping at the reward-associated location. But these mice headed straight for the location, suggesting a conscious memory. “The mouse develops a goal-directed behaviour to go towards the place,” says Benchenane. “It proves that it’s not an automatic behaviour. What we create is an association between a particular place and a reward that can be consciously accessed by the mouse.”

“The mouse is remembering enough abstract information to think ‘I want to go to a certain place’, and go there when it wakes up,” says neuroscientist Neil Burgess at University College London. “It’s a bigger breakthrough [than previous studies] because it really does show what the man in the street would call a memory – the ability to bring to mind abstract knowledge which can guide behaviour in a directed way.”

Benchenane doesn’t think the technique can be used to implant many other types of memories, such as skills – at least for the time being. Spatial memories are easier to modify because they are among the best understood.

His team’s findings also provide some of the strongest evidence for the way in which place cells work. It is almost impossible to test whether place cells function as an internal map while animals are awake, says Benchenane, because these animals also use external cues, such as landmarks, to navigate. By specifically targeting place cells while the mouse is asleep, the team were able to directly test theories that specific cells represent specific places.

“Even when those place cells fire in sleep, they still convey spatial information,” says Benchenane. “That provides evidence that when you’ve got activation of place cells during the consolidation of memories in sleep, you’ve got consolidation of the spatial information.”

Benchenane hopes that his technique could be developed to help alter people’s memories, perhaps of traumatic events (see “Now it’s our turn”, below).

Loren Frank at the University of California, San Francisco, agrees. “I think this is a really important step towards helping people with memory impairments or depression,” he says. “It is surprising to me how many neurological and psychiatric illnesses have something to do with memory, including schizophrenia and obsessive compulsive disorder.”

“In principle, you could selectively change brain processing during sleep to soften memories or change their emotional content,” he adds.

Journal reference: Nature Neuroscience, doi:10.1038/nn.3970

http://www.newscientist.com/article/dn27115-new-memories-implanted-in-mice-while-they-sleep.html#.VP_L9uOVquD

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

Brain decoder can eavesdrop on your inner voice

brainy_2758840b

Talking to yourself used to be a strictly private pastime. That’s no longer the case – researchers have eavesdropped on our internal monologue for the first time. The achievement is a step towards helping people who cannot physically speak communicate with the outside world.

“If you’re reading text in a newspaper or a book, you hear a voice in your own head,” says Brian Pasley at the University of California, Berkeley. “We’re trying to decode the brain activity related to that voice to create a medical prosthesis that can allow someone who is paralysed or locked in to speak.”

When you hear someone speak, sound waves activate sensory neurons in your inner ear. These neurons pass information to areas of the brain where different aspects of the sound are extracted and interpreted as words.

In a previous study, Pasley and his colleagues recorded brain activity in people who already had electrodes implanted in their brain to treat epilepsy, while they listened to speech. The team found that certain neurons in the brain’s temporal lobe were only active in response to certain aspects of sound, such as a specific frequency. One set of neurons might only react to sound waves that had a frequency of 1000 hertz, for example, while another set only cares about those at 2000 hertz. Armed with this knowledge, the team built an algorithm that could decode the words heard based on neural activity alone (PLoS Biology, doi.org/fzv269).

The team hypothesised that hearing speech and thinking to oneself might spark some of the same neural signatures in the brain. They supposed that an algorithm trained to identify speech heard out loud might also be able to identify words that are thought.

Mind-reading

To test the idea, they recorded brain activity in another seven people undergoing epilepsy surgery, while they looked at a screen that displayed text from either the Gettysburg Address, John F. Kennedy’s inaugural address or the nursery rhyme Humpty Dumpty.

Each participant was asked to read the text aloud, read it silently in their head and then do nothing. While they read the text out loud, the team worked out which neurons were reacting to what aspects of speech and generated a personalised decoder to interpret this information. The decoder was used to create a spectrogram – a visual representation of the different frequencies of sound waves heard over time. As each frequency correlates to specific sounds in each word spoken, the spectrogram can be used to recreate what had been said. They then applied the decoder to the brain activity that occurred while the participants read the passages silently to themselves.

Despite the neural activity from imagined or actual speech differing slightly, the decoder was able to reconstruct which words several of the volunteers were thinking, using neural activity alone (Frontiers in Neuroengineering, doi.org/whb).

The algorithm isn’t perfect, says Stephanie Martin, who worked on the study with Pasley. “We got significant results but it’s not good enough yet to build a device.”

In practice, if the decoder is to be used by people who are unable to speak it would have to be trained on what they hear rather than their own speech. “We don’t think it would be an issue to train the decoder on heard speech because they share overlapping brain areas,” says Martin.

The team is now fine-tuning their algorithms, by looking at the neural activity associated with speaking rate and different pronunciations of the same word, for example. “The bar is very high,” says Pasley. “Its preliminary data, and we’re still working on making it better.”

The team have also turned their hand to predicting what songs a person is listening to by playing lots of Pink Floyd to volunteers, and then working out which neurons respond to what aspects of the music. “Sound is sound,” says Pasley. “It all helps us understand different aspects of how the brain processes it.”

“Ultimately, if we understand covert speech well enough, we’ll be able to create a medical prosthesis that could help someone who is paralysed, or locked in and can’t speak,” he says.

Several other researchers are also investigating ways to read the human mind. Some can tell what pictures a person is looking at, others have worked out what neural activity represents certain concepts in the brain, and one team has even produced crude reproductions of movie clips that someone is watching just by analysing their brain activity. So is it possible to put it all together to create one multisensory mind-reading device?

In theory, yes, says Martin, but it would be extraordinarily complicated. She says you would need a huge amount of data for each thing you are trying to predict. “It would be really interesting to look into. It would allow us to predict what people are doing or thinking,” she says. “But we need individual decoders that work really well before combining different senses.”

http://www.newscientist.com/article/mg22429934.000-brain-decoder-can-eavesdrop-on-your-inner-voice.html

New research may help explain why curiosity promotes better memory

Everyone knows it’s easier to learn about a topic you’re curious about. Now, a new study reveals what’s going on in the brain during that process, revealing that such curiosity may give a person a memory boost.

When participants in the study were feeling curious, they were better at remembering information even about unrelated topics, and brain scans showed activity in areas linked to reward and memory.

The results, detailed October 2 in the journal Neuron, hint at ways to improve learning and memory in both healthy people and those with neurological disorders, the researchers said.

“Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” Matthias Gruber, a memory researcher at the University of California, Davis, said in a statement. “These findings suggest ways to enhance learning in the classroom and other settings.”

Gruber and his colleagues put people in a magnetic resonance imaging (MRI) scanner and showed them a series of trivia questions, asking them to rate their curiosity about the answers to those questions. Later, the participants were shown selected trivia questions, then a picture of a neutral face during a 14-second delay, followed by the answer. Afterward, the participants were given a surprise memory test of the faces, and then a memory test of the trivia answers.

Not surprisingly, the study researchers found that people remembered more information about the trivia when they were curious about the trivia answers. But unexpectedly, when the participants were curious, they were also better at remembering the faces, an entirely unrelated task. Participants who were curious were also more likley than others to remember both the trivia information and unrelated faces a day later, the researchers found.

The brain scans showed that, compared with when their curiosity wasn’t piqued, when people were curious, they showed more activation of brain circuits in the nucleus accumbens, an area involved in reward. These same circuits, mediated by the neurochemical messenger dopamine, are involved in forms of external motivation, such as food, sex or drug addiction.

Finally, being curious while learning seemed to produce a spike of activity in the hippocampus, an area involved in forming new memories, and strengthened the link between memory and reward brain circuits.

The study’s findings not only highlight the importance of curiosity for learning in healthy people, but could also give insight into neurological conditions. For example, as people age, their dopamine circuits tend to deteriorate, so understanding how curiosity affects these circuits could help scientists develop treatments for patients with memory disorders, the researchers said.

http://www.livescience.com/48121-curiosity-boosts-memory-learning.html

Our Brains Immediately Judge the Trustworthiness of People

Brain, artwork

Even if we cannot consciously see a person’s face, our brain is able to make a snap decision about how trustworthy they are.

According to a new study published in the Journal of Neuroscience, the brain immediately determines how trustworthy a face is before it’s fully perceived, which supports the fact that we make very fast judgments about people.

Researchers at Dartmouth College and New York University showed a group of participants photos of real people’s faces, as well as computer-generated faces that were meant to look either trustworthy or untrustworthy. It’s been shown in the past that people generally think that faces with high inner eyebrows and prominent cheekbones are more trustworthy, and the opposite features are untrustworthy, which the researchers were able to confirm.

In a second part of their experiment, the researchers showed a separate group of participants the same images but for only about 30 milliseconds while they were in a brain scanner. They then did something called “backward masking,” which consists of showing a participant an irrelevant image or “mask” immediately after quickly showing them a face. The procedure makes the brain incapable of processing the face.

Even though the patients were not able to process the faces, their brains did. The researchers focused on activity in the amygdala, a part of the brain responsible for social and emotional behavior, and found that specific areas of the amygdala were activated based on judgments of trustworthiness or non-trustworthiness. This, the researchers conclude, is evidence that our brains make judgments of people before we even process who they are or what they look like.

Thanks to Pete Cuomo for bringing this to the attention of the It’s Interesting community.

http://time.com/?xid=newsletter-brief#3083667/brain-trustworthiness/

7 Very Bizarre (and Very Rare) Psychotic Hallucinations

brain

The many documented cases of strange delusions and neurological syndromes can offer a window into how bizarre the brain can be.

It may seem that hallucinations are random images that appear to some individuals, or that delusions are thoughts that arise without purpose. However, in some cases, a specific brain pathway may create a particular image or delusion, and different people may experience the same hallucination.

In recent decades, with advances in brain science, researchers have started to unravel the causes of some of these conditions, while others have remained a mystery.

Here is a look at seven odd hallucinations, which show that anything is possible when the brain takes a break from reality.

1. Alice-in-Wonderland syndrome
This neurological syndrome is characterized by bizarre, distorted perceptions of time and space, similar to what Alice experienced in Lewis Carroll’s “Alice’s Adventures in Wonderland.”

Patients with Alice-in-Wonderland syndrome describe seeing objects or parts of their bodies as smaller or bigger than their actual sizes, or in an altered shape. These individuals may also perceive time differently.

The rare syndrome seems to be caused by some viral infections, epilepsy, migraine headaches and brain tumors. Studies have also suggested that abnormal activity in parts of the visual cortex that handle information about the shape and size of objects might cause the hallucinations.

It’s also been suggested that Carroll himself experienced the condition during migraine headaches and used them as inspiration for writing the tale of Alice’s strange dream.

English psychiatrist John Todd first described the condition in an article published in the Canadian Medical Association Journal in 1955, and that’s why the condition is also called Todd’s syndrome. However, an earlier reference to the condition appears in a 1952 article by American neurologist Caro Lippman. The doctor describes a patient who reported feeling short and wide as she walked, and referenced “Alice’s Adventures in Wonderland” to explain her body image illusions.

2. Walking Corpse Syndrome
This delusion, also called Cotard’s Syndrome, is a rare mental illness in which patients believe they are dead, are dying or have lost their internal organs.

French neurologist Jules Cotard first described the condition in 1880, finding it in a woman who had depression and also symptoms of psychosis. The patient believed she didn’t have a brain or intestines, and didn’t need to eat. She died of starvation.

Other cases of Cotard’s syndrome have been reported in people with a range of psychiatric and neurological problems, including schizophrenia, traumatic brain injury and multiple sclerosis.

In a recent case report of Cotard’s syndrome, researchers described a previously healthy 73-year-old woman who went to the emergency room insisting that she was “going to die and going to hell.” Eventually, doctors found the patient had bleeding in her brain due to a stroke. After she received treatment in the hospital, her delusion resolved within a week, according to the report published in January 2014 in the journal of Neuropsychiatry.

3. Charles Bonnet syndrome
People who have lost their sight may develop Charles Bonnet syndrome, which involves having vivid, complex visual hallucinations of things that aren’t really there.

People with this syndrome usually hallucinate people’s faces, cartoons, colored patterns and objects. It is thought the condition occurs because the brain’s visual system is no longer receiving visual information from the eye or part of the retina, and begins making up its own images.

Charles Bonnet syndrome occurs in between 10 and 40% of older adults who have significant vision loss, according to studies.

4. Clinical lycanthropy
In this extremely rare psychiatric condition, patients believe they are turning into wolves or other animals. They may perceive their own bodies differently, and insist they are growing the fur, sharp teeth and claws of a wolf.

Cases have also been reported of people with delusional beliefs about turning into dogs, pigs, frogs and snakes.

The condition usually occurs in combination with another disorder, such as schizophrenia, bipolar disorder or severe depression, according to a review study published in the March issue of the journal History of Psychiatry in 2014.

5. Capgras delusion
Patients with Capgras delusion believe that an imposter has replaced a person they feel close to, such as a friend or spouse. The delusion has been reported in patients with schizophrenia, Alzheimer’s disease, advanced Parkinson’s disease, dementia and brain lesions.

One brain imaging study suggested the condition may involve reduced neural activity in the brain system that processes information about faces and emotional responses.

6. Othello syndrome
Named after Shakespeare’s character, Othello syndrome involves a paranoid belief that the sufferer’s partner is cheating. People with this condition experience strong obsessive thoughts and may show aggression and violence.

In one recent case report, doctors described a 46-year-old married man in the African country Burkina Faso who had a stroke, which left him unable to communicate and paralyzed in half of his body. The patient gradually recovered from his paralysis and speaking problems, but developed a persistent delusional jealousy and aggression toward his wife, accusing her of cheating with an unidentified man.

7. Ekbom’s syndrome
Patients with Ekbom’s syndrome, also known as delusional parasitosis or delusional infestations, strongly believe they are infested with parasites that are crawling under their skin. Patients report sensations of itching and being bitten, and sometimes, in an effort to get rid of the pathogens, they may hurt themselves, which can result in wounds and actual infections.

It’s unknown what causes these delusions, but studies have linked the condition with structural changes in the brain, and some patients have improved when treated with antipsychotic medications.

http://www.livescience.com/46477-oddest-hallucinations.html

Neuroscientist Says NIH Funding Squeeze Causing ‘Crisis’ in Biomedical Enterprise

By Jeannie Baumann

Many scientists now spend more time scrambling to raise money for their work than actually doing the research because of the erosion of NIH funding over the last decade, the president of a biomedical research university said during a June 18 congressional briefing.

Mark Tessier-Lavigne said the 25 percent decline in the National Institutes of Health’s purchasing power has led to grants being funded at historically low rates, causing promising young scientists to leave the field altogether and threatening the future of the biomedical research workforce.

“The financial squeeze has triggered a crisis in the biomedical research enterprise,” according to Tessier-Lavigne, who is president of the Rockefeller University in New York and investigates how neural circuits in the brain form during embryonic development. “Renewing NIH funding is an essential investment, not just for our health, but also for our economy.”

Tessier-Lavigne was the main speaker at the Capitol Hill briefing, “Paying Dividends: How Federally Funded Biomedical Research Fuels the Pharmaceutical Industry in the U.S.,” which was organized by the Coalition for the Life Sciences and theCongressional Biomedical Research Caucus as part of the 2014 caucus briefing series.

The key point of Tessier-Lavigne’s presentation—that scientific opportunity has never been greater while federal funding for basic research is at a low—has been echoed, especially by NIH Director Francis S. Collins when testifying before lawmakers in both the House and the Senate.

“We live in a golden age of biological research, of disease research, and of drug discovery that’s been enabled by a revolution in the biosciences that’s occurred over the past 40 years, thanks to the development of very powerful technologies,” said Tessier-Lavigne, citing as examples recombinant DNA, gene sequencing, human genetics and imaging. “We can now tackle disease systematically and that is enabling systematic drug discovery.”

The research ecosystem requires early investment through NIH funding to academia to yield the treatments and cures from the pharmaceutical industry, Tessier-Lavigne said.

“There’s a division of labor,” he said. “Most of the scientific discovery that leads to the insights that are built upon are made in academia, in research labs, in research institutes, in universities supported by the NIH. At the other end of the spectrum, industry—mostly large pharmaceutical companies and large biotech companies—are responsible for making the drugs and taking them through human clinical trials.”

Tessier-Lavigne has worked at both ends of the spectrum, serving as chief scientific officer at biotechnology company Genentech before taking over at Rockefeller. He rejected the idea that drug companies could take on funding the basic research. The cost and time lines of drug discovery and development are already too great, he said.

“To make a drug, to get a drug approved there’s huge attritions,” he said. The process starts with targeting 24 projects, and scientists try to make drugs to fight them that yields on average about nine drug candidates that make it into clinical trials.

“But of those nine, only a single one will make it over the finish line as an approved drug,” he said.

That drug-making process takes an average of 13 years, including five years to make the drug candidates and eight years to get to clinical approval. Including failures, he estimated those costs at anywhere between $2 billion to $4 billion per drug.

“So companies that do this are already struggling to succeed just at this. There are no more resources to fund the ferment back here that leads to the identification of new knowledge. The companies can’t do it and they won’t do it,” he said.

“Couldn’t we just rely on other nations to generate the basic knowledge and then industry here could continue to do the translational work?” Tessier-Lavigne asked rhetorically.

“Well, that’s not how it works. Industry wants its R&D [research and development] sites to be located next to the sites of innovation. It’s as simple as that,” he said.

Over the past 30 years, Tessier-Lavigne said, there has been a “massive” transfer of industry from Europe to the U.S. because of the prominence of the U.S. biomedical enterprise.

“If we don’t maintain, sustain our investment in our basic biomedical enterprise, industry will pick up and move to the other sites,” he said, adding that countries like China are where these companies will move, taking jobs with them.
Rep. Jackie Speier (D-Calif.), co-chairman of the Congressional Biomedical Research Caucus, also mentioned that the U.S. may lose its position as the leader in R&D.

“We still lead in terms of patents and overall research, but China is about to eat our lunch,” said Speier, whose district includes the Bay Area and Genentech’s headquarters. “In fact, China has just about eclipsed Japan now in terms of research and within the next 10 years, it is anticipated that they will indeed overcome us in terms of research and development. And that would indeed be a tragic set of circumstances.”
Action Plan

Tessier-Lavigne proposed an action plan that primarily involves gradually restoring NIH funding in absolute dollars to its 2003 level—the final year of a five-year doubling. Since the 2003 doubling, the NIH’s budget has remained flat at about $30 billion. Collins has said that his agency would have about a $40 billion annual budget if the NIH had continued to receive the steady, 3 percent increases it received from the 1970s onward.

Restoring funding to the 2003 levels would relieve the squeeze on existing programs so scientists can focus on their work as well as stimulate new initiatives to accelerate progress and open new areas of discovery, Tessier-Lavigne said.

At the same time, the academic sector has a responsibility to make sure it spends these dollars effectively while developing a pipeline of new talent. And all stakeholders—academia, the NIH, disease foundations and the private sector—must ensure research discoveries are effectively translated into new therapies and cures.

The next congressional briefing is scheduled for July 16 on the advances and potential of embryonic stem cell research, withLawrence Goldstein, director of the University of California, San Diego, Stem Cell Program.

Thanks to Pete Cuomo for bringing this to the attention of the It’s Interesting community.

Brief History of 8 Hallucinogens

Humans have been ingesting mind-altering substances for a very long time. Hallucinogen-huffing bowls 2,500 years old (http://www.livescience.com/5240-ancient-family-heirlooms-snort-hallucinogens.html) have been found on islands in the Lesser Antilles, and traditional cultures from the Americas to Africa use hallucinogenic substances for spiritual purposes. Here are some notable substances that send the mind tripping.

LSD is commonly known as “acid,” but its scientific name is a mouthful: lysergic acid diethylamaide. The drug was first synthesized in 1938 from a chemical called ergotamine. Ergotamine, in turn, is produced by a grain fungus that grow on rye.

LSD was originally produced by a pharmaceutical company under the name Delysid, but it got a bad reputation in the 1950s when the CIA decided to research its effects on mind control. The test subjects of the CIA project MKULTRA proved very difficult to control indeed, and many, like counter-culture writer Ken Kesey, started taking the drug for fun (and for their own form of 1960s enlightenment).

ayahuasca-vine-110929

Ayahuasca is a hallucinatory mixture of Amazonian infusions centered around the Banisteriopsis caapi vine. The brew has long been used by native South American tribes for spiritual rituals and healing, and like other hallucinogens, ayahuasca often triggers very intense emotional experiences (vomiting is also common). In 2006, National Geographic writer Kira Salak described her experience with ayahuasca in Peru for the magazine.

” I will never forget what it was like. The overwhelming misery. The certainty of never-ending suffering. No one to help you, no way to escape. Everywhere I looked: darkness so thick that the idea of light seemed inconceivable,” Salak wrote. “Suddenly, I swirled down a tunnel of fire, wailing figures calling out to me in agony, begging me to save them. Others tried to terrorize me. ‘You will never leave here,’ they said. ‘Never. Never.'”

Nonetheless, Salak wrote, when she broke free of her hallucinations, her crippling depression was alleviated. It’s anecdotal experiences like this that have led researchers to investigate the uses of hallucinogens as therapy for mental disorders such as anxiety, depression and post-traumatic stress disorder.

Peyote is a cactus that gets its hallucinatory power from mescaline. Like most hallucinogens, mescaline binds to serotonin receptors in the brain, producing heightened sensations and kaleidoscopic visions.

Native groups in Mexico have used peyote in ceremonies for thousands of years, and other mescaline-producing cacti have long been used by South American tribes for their rituals. Peyote has been the subject of many a court battle because of its role in religious practice; currently, Arizona, Colorado, New Mexico, Nevada and Oregon allow some peyote possession, but only if linked to religious ceremonies, according to Arizona’s Peyote Way Church of God.

The “magic” ingredient in hallucinogenic mushrooms is psilocybin, a compound that breaks down into psilocin in the body. Psilocin bonds to serotonin receptors all over the brain, and can cause hallucinations as well as synesthesia, or the mixture of two senses. Under the influence, for example, a person might feel that they can smell colors.

In keeping with the human tradition of eating anything that might alter your mind, people have been ingesting psilocybin-continuing mushrooms for thousands of years. Synthetic psilocybin is now under study as a potential treatment for anxiety, depression and addiction.

Best known by its street name, “angel dust,” PCP stands for phencyclidine. The drug blocks receptors in the brain for the neurotransmitter glutamate. It’s more dangerous than other hallucinogens, with schizophrenia-like symptoms and nasty side effects.

Those side effects are why PCP has no medical uses. The drug was tested as an anesthetic in the 1950s and used briefly to knock out animals during veterinary surgeries. But by the 1960s, PCP had hit the streets and was being used as a recreation drug, famous for the feelings of euphoria and invincibility it bestowed on the user. Unfortunately, a side effect of all that euphoria is sometimes truly destructive behavior, including users trying to jump out of windows or otherwise self-mutilating. Not to mention that high enough doses can cause convulsions.

Derived from the African iboga plant, ibogaine is another hallucinogen with a long history of tribal use. More recently, the drug has shown promise in treating addiction, although mostly in Mexico and Europe where ibogaine treatment is not prohibited as it is in the U.S.

Using ibogaine as therapy is tricky, however. The drug can cause heart rhythm problems, and vomiting is a common side effect. The Massachusetts-based Multidisciplinary Association for Psychedelic Research (MAPS) reports that an estimated 1 in 300 ibogaine users die due to the drug. The group is studying the long-term effects of ibogaine on patients in drug treatment programs in New Zealand and Mexico.

Salvia divinorum, also known as seer’s or diviner’s sage, grows in the cloud forest of Oaxaca, Mexico. The native Mazatec people have long used tea made out of the leaves in spiritual ceremonies, but the plant can also be smoked or chewed for its hallucinogenic effects.

Salvia is not currently a controlled substance, according to the National Institute on Drug Abuse, but it is under consideration to be made illegal and placed in the same drug class as marijuana.

Ecstasy, “E” or “X” are the street names for MDMA, or (get ready for a long one) 3,4-methylenedioxymethamphetamine. The drug acts on serotonin in the brain, causing feelings of euphoria, energy and distortions of perception. It can also nudge body temperatures up, raising the risk of heat stroke. Animal studies suggest that MDMA causes long-term and potentially dangerous changes in the brain, according to the National Institute on Drug Abuse.

MDMA was first synthesized by a chemist looking for substances to stop bleeding in 1912. No one paid the compound much mind for the next half-decade, but by the 1970s, MDMA had hit the streets. It was popular at raves and nightclubs and among those who liked their music psychedelic. Today, ecstasy is still a common street drug, but researchers are investigating whether MDMA could be used to treat post-traumatic stress disorder and cancer-related anxiety.

http://www.livescience.com/16286-hallucinogens-lsd-mushrooms-ecstasy-history.html

Mice run for fun on wheels out in the wild.

By James Gorman

If an exercise wheel sits in a forest, will mice run on it?

Every once in a while, science asks a simple question and gets a straightforward answer.

In this case, yes, they will. And not only mice, but also rats, shrews, frogs and slugs.

True, the frogs did not exactly run, and the slugs probably ended up on the wheel by accident, but the mice clearly enjoyed it. That, scientists said, means that wheel-running is not a neurotic behavior found only in caged mice.

They like the wheel.

Two researchers in the Netherlands did an experiment that it seems nobody had tried before. They placed exercise wheels outdoors in a yard and in an area of dunes, and monitored the wheels with motion detectors and automatic cameras.

They were inspired by questions from animal welfare committees at universities about whether mice were really enjoying wheel-running, an activity used in all sorts of studies, or were instead like bears pacing in a cage, stressed and neurotic. Would they run on a wheel if they were free?

Now there is no doubt. Mice came to the wheels like human beings to a health club holding a spring membership sale. They made the wheels spin. They hopped on, hopped off and hopped back on.

“When I saw the first mice, I was extremely happy,” said Johanna H. Meijer at Leiden University Medical Center in the Netherlands. “I had to laugh about the results, but at the same time, I take it very seriously. It’s funny, and it’s important at the same time.”

Dr. Meijer’s day job is as a “brain electrophysiologist” studying biological rhythms in mice. She relished the chance to get out of the laboratory and study wild animals, and in a way that no one else had.

She said Konrad Lorenz, the great-grandfather of animal behavior studies, once mentioned in a letter that some of his caged rats had escaped and then returned to his garden to use running wheels placed there.

But, Dr. Meijer said, the Lorenz observation “was one sentence.”

For the experiment, the wheels were enclosed so that small animals could come and go but so that larger animals could not knock them over. Dr. Meijer set up motion sensors and automatic video cameras. Several years and 12,000 snippets of video later, she and Yuri Robbers, also a Leiden researcher, reported the results. They were released in the Proceedings of the Royal Society B.

Gene D. Block, chancellor of the University of California, Los Angeles, was not involved with the paper but knows Dr. Meijer and had seen the wheel set up in her garden. He said the study made it clear that wheel-running is “some type of rewarding behavior” and “probably not driven by stress or anxiety.”

Mice accounted for 88 percent of the wheel-running events, and spent one minute to 18 on the wheel. The other animals each accounted for less than 1 percent. Frogs, though there were very few, were seen to get on the wheel, get off and get back on.

Russell Foster, a circadian rhythm researcher at Oxford University, said he read the paper and sent it out to other scientists on behalf of the Proceedings and was delighted when peer reviews from other scientists were positive.

Marc Bekoff, a professor of ecology and evolutionary biology at the University of Colorado who is active in the animal welfare movement, said in an email that he thought the paper did show that wheel-running could be a “voluntary activity,” but that mice in labs may be doing more of it because of the stress of confinement.

“Wild bears will often pace back and forth,” he wrote, “but in captivity, the rate of doing it seems to be greatly heightened.”

As to why the mice, frogs or perhaps even slugs run, or move, on the wheel, Dr. Meijer said she thought that “there is an intrinsic motivation for animals, or should I say organisms, to be active.”

Huda Akil, co-director of the Molecular and Behavioral Neuroscience Institute at the University of Michigan, who has studied reward systems, said: “It’s not a surprise. All you have to do is watch a bunch of little kids in a playground or a park. They run and run and run.”

Dr. Akil said that in humans, running activates reward pathways in the brain, although she pointed out that there are innate differences in temperament in all sorts of animals, including humans. Rats that do not like to run can be bred. And plenty of people do all they can to avoid jogging, cycling and elliptical machines.

Presumably, the same is true of wild mice. While some were setting the wheel on fire with their exertions, others, out of camera range, may have been sprawled out on the mouse equivalent of a lounge chair, shaking their whiskers in dismay and disbelief.

Thanks to Dr. Nakamura for bringing this to the attention of the It’s Interesting community.

Parenting Rewires the Male Brain

By Elizabeth Norton

Cultures around the world have long assumed that women are hardwired to be mothers. But a new study suggests that caring for children awakens a parenting network in the brain—even turning on some of the same circuits in men as it does in women. The research implies that the neural underpinnings of the so-called maternal instinct aren’t unique to women, or activated solely by hormones, but can be developed by anyone who chooses to be a parent.

“This is the first study to look at the way dads’ brains change with child care experience,” says Kevin Pelphrey, a neuroscientist at Yale University who was not involved with the study. “What we thought of as a purely maternal circuit can also be turned on just by being a parent—which is neat, given the way our culture is changing with respect to shared responsibility and marriage equality.”

The findings come from an investigation of two types of households in Israel: traditional families consisting of a biological mother and father, in which the mother assumed most of the caregiving duties, though the fathers were very involved; and homosexual male couples, one of whom was the biological father, who’d had the child with the help of surrogate mothers. The two-father couples had taken the babies home shortly after birth and shared caregiving responsibilities equally. All participants in the study were first-time parents.

Researchers led by Ruth Feldman, a psychologist and neuroscientist at Bar-Ilan University in Ramat Gan, Israel, visited with the families in their homes, videotaping each parent with the child and then the parents and children alone. The team, which included collaborators at the Tel Aviv Sourasky Medical Center in Israel, also took saliva samples from all parents before and after the videotaped sessions to measure oxytocin—a hormone that’s released at times of intimacy and affection and is widely considered the “trust hormone.” Within a week of the home visit, the participants underwent functional magnetic resonance imaging scanning to determine how their brains reacted to the videotapes of themselves with their infants.

The mothers, their husbands, and the homosexual father-father couples all showed the activation of what the researchers term a “parenting network” that incorporated two linked but separate pathways in the brain. One circuit encompasses evolutionarily ancient structures such as the amygdala, insula, and nucleus accumbens, which handle strong emotions, attention, vigilance, and reward. The other pathway turns up in response to learning and experience and includes parts of the prefrontal cortex and an area called the superior temporal sulcus.

In the mothers, activation was stronger in the amygdala-centered network, whereas the heterosexual fathers showed more activity in the network that’s more experience-dependent. At first glance, Feldman says, the finding would seem to suggest that mothers are more wired up to nurture, protect, and possibly worry about their children. The fathers, in contrast, might have to develop these traits through tending, communicating, and learning from their babies what various sounds mean and what the child needs.

“It’s as if the father’s amygdala can shut off when there’s a woman around,” Feldman observes. It could be assumed, she says, that this circuitry is activated only by the rush of hormones during conception, pregnancy, and childbirth.

But the brains of the homosexual couples, in which each partner was a primary caregiver, told a different story. All of these men showed activity that mirrored that of the mothers, with much higher activation in the amygdala-based network, the team reports online today in the Proceedings of the National Academy of Sciences.

This finding argues strongly that the experience of hands-on parenting, with no female mother anywhere in the picture, can configure a caregiver’s brain in the same way that pregnancy and childbirth do, Feldman says.

She adds that in the heterosexual fathers, the activation of the amygdala-based network was proportional to the amount of time they spent with the baby, though the activity wasn’t as high as in the mothers or in the two-father couples.

Feldman does not believe that the brain activity of the primary-caregiving fathers differed because they were gay. Previous imaging studies, she notes, show no difference in brain activation when homosexual and heterosexual participants viewed pictures of their loved ones.

Future studies, Pelphrey says, might focus more closely on this question. “But it’s clear that we’re all born with the circuitry to help us be sensitive caregivers, and the network can be turned up through parenting.”

http://news.sciencemag.org/brain-behavior/2014/05/parenting-rewires-male-brain