Neurodegeneration’s Spread

Aggregates of the Huntington’s disease-associated protein, huntingtin, can spread among neurons, according to a study published last month  in Nature Neuroscience, giving credence, experts suggest, to the idea that the propagation of mutant proteins may be a unifying feature of neurodegenerative diseases.

Huntington’s disease, a progressive neurodegenerative disorder that impairs both movement and cognition, is caused by dominant mutations in the huntingtin gene that lead to abnormally long stretches of the amino acid glutamine in the huntingtin protein. These proteins tend to clump in affected neurons, although whether the aggregates are a cause of neurodegeneration or perhaps some kind of cellular response to the mutant protein is still a matter of debate.

The huntingtin gene is expressed throughout the nervous system, so it is hard to tell whether huntingtin aggregates originate within the cells in which they are observed.

To answer this question, researchers from the Novartis Institutes for Biomedical Research in Basel, Switzerland, and their academic colleagues introduced neurons with the wild-type huntingtin gene into mutant brain tissue—both in cell culture and in a mouse model. After several weeks, they observed that aggregates of mutant huntingtin protein had appeared in the wild-type neurons, indicating that the protein from the mutant neurons had spread.

“This paper reports for the first time that mutant huntingtin can spread between neurons,” lead author F. Paolo Di Giorgio, who studies Huntington’s and other neurodegenerative diseases at the Novartis Institutes, told The Scientist.

Neurodegenerative diseases including Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS), and frontotemporal lobar degeneration have been shown to involve the propagation of aggregate pathology from cell to cell. Evidence is mounting that neurodegenerative diseases share mechanisms with prion diseases—exemplified by mad cow disease and its human counterpart, Creutzfeldt-Jakob disease, in which misfolded, deleterious proteins propagate over long distances and cause other molecules to misfold.

“This is the first time that diseases involving what are called polyglutamine-expanded proteins have been found to involve a process of transneuronal propagation,” said Albert La Spada, who studies neurodegenerative disease at the University of California, San Diego, School of Medicine and penned a companion article about the study but was not involved in the work. Polyglutamine expansion is a feature of eight neurodegenerative diseases, including Huntington’s, La Spada said. “That’s significant because it extends the scope of this mechanism more broadly across potentially all neurodegenerative diseases. That’s what makes this study particularly exciting.”

To see if huntingtin aggregates could propagate, the researchers first grew human embryonic stem cells alongside brain slices from either mice with a Huntington’s-like disease or wild-type mice. The stem cells differentiated into neurons and formed connections with the mutant neurons of the brain slices.  By six weeks of this co-culture, the introduced wild-type neurons exhibited mutant huntingtin aggregates. They also had shorter and fewer appendages than did neurons co-cultured with wild-type brain slices. Further, introduced neurons that exhibited huntingtin aggregates had significantly narrower cell bodies and fewer projections than those that did not.

“Cells that bear these aggregates show abnormal pathology that is more pronounced [with] respect to cells that don’t bear the aggregates,” said Di Giorgio, “so it seems that when the neurons uptake mutant huntingtin—wild-type neurons that don’t carry any mutation—they will start to show signs of cellular atrophy.”

Huntington’s disease typically begins in the striatum, a brain region involved in movement control, and progresses to the cortex. To examine the way Huntington’s disease might affect this neuronal pathway, the researchers co-cultured striatal and cortical brain slices from wild-type and mutant mice. They found that when mutant cortical neurons and wild-type striatal brain slices were cultured together, functional neuronal connections formed between the brain slices, and mutant huntingtin spread to the wild-type neurons.

When researchers tried the reverse approach—linking mutant striatum and wild-type cortex—the two regions did not form neuronal connections, suggesting that mutant huntingtin within the striatum could disrupt corticostriatal connections.

To explore the corticostriatal pathway in vivo, the researchers used a virus to introduce the polyglutamine-repeat-encoding part of the huntingtin gene into the cortical neurons of wild-type mice. The neurons that were infected with the virus developed aggregates as expected, as did the striatal neurons with which the infected cells made connections.

Finally, in order to probe the mechanism of mutant huntingtin spreading, the researchers returned to their original experimental setup—co-cultures of wild-type human neurons and mutant mouse brain slices—and inhibited the synaptic vesicle pathway using botulinum toxin. Blocking the synaptic transmission reduced the spread of the huntingtin aggregates.  

Taken together, these results lend support to the idea that Huntington’s disease shares features with other neurodegenerative diseases, and with prion diseases.

“If neurodegenerative diseases have a unifying feature,” neurobehavioral geneticist X. William Yang from the University of California, Los Angeles, told The Scientist in an e-mail, “then understand[ing] the mechanisms or developing therapies against such common features may have more general implications/utility for all such disorders.” 

“If spreading occurs and drives disease progression, then blocking the spreading process could be a viable treatment approach,” added La Spada. “If the spreading process occurs extracellularly … then immunizing patients against a disease protein could be explored as a therapy.”

Outside views are often badges of seniority or achievement in the work world… But new evidence suggests employers should look at daylight exposure less as a mark of accomplishment and more as a matter of public health. So says an interdisciplinary team of architects and medical researchers that recently conducted a small case study comparing people exposed to natural light at their jobs with those who aren’t. The window workers scored better on common self-report health and sleep surveys; they also slept 46 minutes more a night, on average, as measured by a sleep monitor.

Researchers find that windowless offices make workers lose sleep at night – which makes sense given how important daylight exposure is to regulating our internal clocks

Ongoing coverage of sleep here.

(via explore-blog)

How playing an instrument benefits your brain

Recent research about the mental benefits of playing music has many applications, such as music therapy for people with emotional problems, or helping to treat the symptoms of stroke survivors and Alzheimer’s patients. But it is perhaps even more significant in how much it advances our understanding of mental function, revealing the inner rhythms and complex interplay that make up the amazing orchestra of our brain.
Did you know that every time musicians pick up their instruments, there are fireworks going off all over their brain? On the outside they may look calm and focused, reading the music and making the precise and practiced movements required. But inside their brains, there’s a party going on.

From the TED-Ed lesson How playing an instrument benefits your brain - Anita Collins

Animation by Sharon Colman Graham

houseofmind:

Measuring nurture: Study shows how “good mothering” hardwires the infant brain

By carefully watching nearly a hundred hours of video showing mother rats protecting, warming, and feeding their young pups, and then matching up what they saw to real-time electrical readings from the pups’ brains, researchers have found that the mother’s presence and social interactions -— her nurturing role -— directly molds the early neural activity and growth of her offsprings’ brain.
For the study, a half-dozen rat mothers and their litters, of usually a dozen pups, were watched and videotaped from infancy for preset times during the day as they naturally developed. One pup from each litter was outfitted with a miniature wireless transmitter, invisibly placed under the skin and next to the brain to record its electrical patterns.
Specifically, study results showed that when rat mothers left their pups alone in the nest, infant cortical brain electrical activity, measured as local field potentials, jumped 50 percent to 100 percent, and brain wave patterns became more erratic, or desynchronous. Researchers point out that such periodic desynchronization is key to healthy brain growth and communication across different brain regions.
During nursing, infant rat pups calmed down after attaching themselves to their mother’s nipple. Brain activity also slowed and became more synchronous, with clearly identifiable electrical patterns.
However, these brain surges progressively declined during weaning, as infant pups gained independence from their mothers, leaving the nest and seeking food on their own as they grew past two weeks of age.
Additional experiments with a neural-signaling blocking agent, propranolol, confirmed that maternal effects were controlled in part by secretion of norepinephrine, a key neurotransmitter and hormone involved in most basic brain and body functions, including regulation of heart rate and cognition. Noradrenergic blocking in infant rats mostly dampened all previously observed effects induced by their mothers.

More work coming out of the lab :) Click on the title for link to ScienceDaily write-up. 
Source: 
Sarro, Wilson and Sullivan (2014). Maternal Regulation of Infant Brain State. Current Biology 24 (14): 1664-9. 

houseofmind:

Measuring nurture: Study shows how “good mothering” hardwires the infant brain

By carefully watching nearly a hundred hours of video showing mother rats protecting, warming, and feeding their young pups, and then matching up what they saw to real-time electrical readings from the pups’ brains, researchers have found that the mother’s presence and social interactions -— her nurturing role -— directly molds the early neural activity and growth of her offsprings’ brain.

For the study, a half-dozen rat mothers and their litters, of usually a dozen pups, were watched and videotaped from infancy for preset times during the day as they naturally developed. One pup from each litter was outfitted with a miniature wireless transmitter, invisibly placed under the skin and next to the brain to record its electrical patterns.

Specifically, study results showed that when rat mothers left their pups alone in the nest, infant cortical brain electrical activity, measured as local field potentials, jumped 50 percent to 100 percent, and brain wave patterns became more erratic, or desynchronous. Researchers point out that such periodic desynchronization is key to healthy brain growth and communication across different brain regions.

During nursing, infant rat pups calmed down after attaching themselves to their mother’s nipple. Brain activity also slowed and became more synchronous, with clearly identifiable electrical patterns.

However, these brain surges progressively declined during weaning, as infant pups gained independence from their mothers, leaving the nest and seeking food on their own as they grew past two weeks of age.

Additional experiments with a neural-signaling blocking agent, propranolol, confirmed that maternal effects were controlled in part by secretion of norepinephrine, a key neurotransmitter and hormone involved in most basic brain and body functions, including regulation of heart rate and cognition. Noradrenergic blocking in infant rats mostly dampened all previously observed effects induced by their mothers.

More work coming out of the lab :) Click on the title for link to ScienceDaily write-up. 

Source: 

Sarro, Wilson and Sullivan (2014). Maternal Regulation of Infant Brain State. Current Biology 24 (14): 1664-9. 

Has it ever struck you … that life is all memory, except for the one present moment that goes by you so quickly you hardly catch it going? It’s really all memory … except for each passing moment.

Eric Kandel, “In Search of Memory: The Emergence of a New Science of Mind”
Why Does Sleeping In Just Make Me More Tired?
We’ve all been there: It’s been a long week at work, so Friday night, you reward yourself by going to bed early and sleeping in. But when you wake up the next morning (or afternoon), light scathes your eyes, and your limbs feel like they’re filled with sand. Your brain is still lying down and you even have faint headache. If too little sleep is a problem, then why is extra sleep a terrible solution?
Oversleeping feels so much like a hangover that scientists call it sleep drunkenness. But, unlike the brute force neurological damage caused by alcohol, your misguided attempt to stock up on rest makes you feel sluggish by confusing the part of your brain that controls your body’s daily cycle.
Your internal rhythms are set by your circadian pacemaker, a group of cells clustered in the hypothalamus, a primitive little part of the brain that also controls hunger, thirst, and sweat. Primarily triggered by light signals from your eye, the pacemaker figures out when it’s morning and sends out chemical messages keeping the rest of the cells in your body on the same clock.
Scientists believe that the pacemaker evolved to tell the cells in our bodies how to regulate their energy on a daily basis. When you sleep too much, you’re throwing off that biological clock, and it starts telling the cells a different story than what they’re actually experiencing, inducing a sense of fatigue. You might be crawling out of bed at 11am, but your cells started using their energy cycle at seven. This is similar to how jet lag works.
But oversleep isn’t just going to ruin your Saturday hike. If you’re oversleeping on the regular, you could be putting yourself at risk for diabetes, heart disease, and obesity. Harvard’s massive Nurses Health Study found that people who slept 9 to 11 hours a night developed memory problems and were more likely to develop heart disease than people who slept a solid eight. (Undersleepers are at an even bigger risk). Other studies have linked oversleep to diabetes, obesity, and even early death.
Oversleep doesn’t just happen as a misguided attempt at rewarding yourself. The Harvard Nurses Study estimated that chronic oversleep affects about 4 percent of the population. These are generally people who work odd hours, have an uncomfortable sleep situation, or a sleeping disorder.
People who work early morning or overnight shifts might be oversleeping to compensate for waking up before the sun rises or going to sleep when it’s light out. Doctors recommend using dark curtains and artificial lights to straighten things out rather than medication or supplements. Apps like the University of Michigan’s Entrain can also help people reset their circadian clock by logging the amount and type of light they get throughout the day.
When you go to bed, your body cycles between different sleep stages. Your muscles, bones, and other tissues do their repair work during deep sleep, before you enter REM. However, if your bed or bedroom is uncomfortable—too hot or cold, messy, or lumpy—your body will spend more time in light, superficial sleep. Craving rest, you’ll sleep longer.
If everything’s just fine with your sleep zone but you still can’t get under the eight hour mark, you might need to go see a doctor. It could be a symptom of narcolepsy, which makes it hard for your body to regulate fatigue and makes you sleep in more. Sleep apnea is a potentially more serious disorder where you stop breathing while you slumber. It’s typically caused by an obstructed airway, which leads to snoring. However, in a small number of sufferers, the brain simply stops telling the muscles to breathe, starving the brain and eventually forcing a gasping response. In addition to all the other terrifying aspects of this disease, it’s not doing your quality of sleep any favors.
No surprise, drugs and alcohol might also be causing you to sleep too much, as does being depressed (In fact, oversleep can contribute to even more depression). But no matter what’s causing it, too much sleep is not good for your long term health. Rather than kicking the can down the road, try getting some equilibrium between your weekend and weekday sleep.

Why Does Sleeping In Just Make Me More Tired?

We’ve all been there: It’s been a long week at work, so Friday night, you reward yourself by going to bed early and sleeping in. But when you wake up the next morning (or afternoon), light scathes your eyes, and your limbs feel like they’re filled with sand. Your brain is still lying down and you even have faint headache. If too little sleep is a problem, then why is extra sleep a terrible solution?

Oversleeping feels so much like a hangover that scientists call it sleep drunkenness. But, unlike the brute force neurological damage caused by alcohol, your misguided attempt to stock up on rest makes you feel sluggish by confusing the part of your brain that controls your body’s daily cycle.

Your internal rhythms are set by your circadian pacemaker, a group of cells clustered in the hypothalamus, a primitive little part of the brain that also controls hunger, thirst, and sweat. Primarily triggered by light signals from your eye, the pacemaker figures out when it’s morning and sends out chemical messages keeping the rest of the cells in your body on the same clock.

Scientists believe that the pacemaker evolved to tell the cells in our bodies how to regulate their energy on a daily basis. When you sleep too much, you’re throwing off that biological clock, and it starts telling the cells a different story than what they’re actually experiencing, inducing a sense of fatigue. You might be crawling out of bed at 11am, but your cells started using their energy cycle at seven. This is similar to how jet lag works.

But oversleep isn’t just going to ruin your Saturday hike. If you’re oversleeping on the regular, you could be putting yourself at risk for diabetes, heart disease, and obesity. Harvard’s massive Nurses Health Study found that people who slept 9 to 11 hours a night developed memory problems and were more likely to develop heart disease than people who slept a solid eight. (Undersleepers are at an even bigger risk). Other studies have linked oversleep to diabetes, obesity, and even early death.

Oversleep doesn’t just happen as a misguided attempt at rewarding yourself. The Harvard Nurses Study estimated that chronic oversleep affects about 4 percent of the population. These are generally people who work odd hours, have an uncomfortable sleep situation, or a sleeping disorder.

People who work early morning or overnight shifts might be oversleeping to compensate for waking up before the sun rises or going to sleep when it’s light out. Doctors recommend using dark curtains and artificial lights to straighten things out rather than medication or supplements. Apps like the University of Michigan’s Entrain can also help people reset their circadian clock by logging the amount and type of light they get throughout the day.

When you go to bed, your body cycles between different sleep stages. Your muscles, bones, and other tissues do their repair work during deep sleep, before you enter REM. However, if your bed or bedroom is uncomfortable—too hot or cold, messy, or lumpy—your body will spend more time in light, superficial sleep. Craving rest, you’ll sleep longer.

If everything’s just fine with your sleep zone but you still can’t get under the eight hour mark, you might need to go see a doctor. It could be a symptom of narcolepsy, which makes it hard for your body to regulate fatigue and makes you sleep in more. Sleep apnea is a potentially more serious disorder where you stop breathing while you slumber. It’s typically caused by an obstructed airway, which leads to snoring. However, in a small number of sufferers, the brain simply stops telling the muscles to breathe, starving the brain and eventually forcing a gasping response. In addition to all the other terrifying aspects of this disease, it’s not doing your quality of sleep any favors.

No surprise, drugs and alcohol might also be causing you to sleep too much, as does being depressed (In fact, oversleep can contribute to even more depression). But no matter what’s causing it, too much sleep is not good for your long term health. Rather than kicking the can down the road, try getting some equilibrium between your weekend and weekday sleep.

9-year-old girl dies from brain-eating amoeba in water

A brain-eating amoeba that lurks in fresh water has prompted warnings from Kansas officials after it killed a 9-year-old girl.

Hally Yust was an avid water skier and spent the past few weeks swimming in several bodies of fresh water. She died last week from Naegleria fowleri, a brain-eating parasite that lives in warm, standing water.

At Hally’s funeral Monday, her family wore matching T-shirts with the logo of her water-skiing club, CNN affiliate WDAF said. Relatives honored the young athlete by announcing the Hally Yust Women’s Basketball Scholarship at Kansas State University.

"Our precious daughter, Hally, loved life and part of her great joy was spending time playing in the water," her family said in a statement.

"Her life was taken by a rare amoeba organism that grows in many different fresh water settings. We want you to know this tragic event is very, very rare, and this is not something to become fearful about."

'It just causes destruction'

While Naegleria fowleri infections are rare, they can have devastating effects.

"The amoeba … finds itself way back in our noses and then can work its way into our central nervous system, around our brains," said Dr. William Schaffner of Vanderbilt University Medical Center. "And once it’s there, it just causes destruction."

Symptoms usually show up five days after infection, the Kansas Department of Health and Environment said.

In addition to a severe headache, fever, nausea and vomiting, Naegleria fowleri infections often cause death.

More frequent in summer

The cases are often reported in the summer, when more swimmers take a dip in fresh water.

Last summer, 12-year-old Zachary Reyna of Florida became infected after he went knee-boarding in fresh water near his home. He later died.

Also last summer, Kali Hardig of Arkansas went for a swim and was infected by the parasite. Despite incredible odds against her, Kali survived.

Over the past 50 years, about 130 Naegleria fowleri infections have been reported. Of those, only three people — including Kali — have survived.

While humans can get infected swimming in fresh water, people cannot get infected from drinking water contaminated with the amoeba, the Centers for Disease Control and Prevention said.

How to protect yourself

The extreme rarity and randomness of infections can make it difficult to predict where they might occur.

"It is unknown why certain persons become infected with (Naegleria fowleri) while millions of others exposed to warm recreational fresh waters do not, including those who were swimming with people who became infected," the CDC said.

The Kansas health department advises swimmers to use nose plugs when swimming in fresh water.

It also suggests not stirring up the sediment at the bottom of shallow freshwater areas and keeping your head above the water in hot springs and other untreated thermal waters.

But Naegleria fowleri is far from the biggest danger in summertime water activities. While 34 people were infected with the amoeba in the U.S. between 2004 and 2013, there were more than 34,000 drowning deaths in the United States between 2001 and 2010, the CDC said.

theartofeviscerator:

Surgical Steel

Beyond Salty and Sweet: A Budding Club of Tastes

Sweet, salty, sour and bitter — every schoolchild knows these are the building blocks of taste. Our delight in every scrumptious bonbon, every sizzling hot dog, derives in part from the tongue’s ability to recognize and signal just four types of taste.

But are there really just four? Over the last decade, research challenging the notion has been piling up. Today, savory, also called umami, is widely recognized as a basic taste, the fifth. And now other candidates, perhaps as many as 10 or 20, are jockeying for entry into this exclusive club.

“What started off as a challenge to the pantheon of basic tastes has now opened up, so that the whole question is whether taste is even limited to a very small number of primaries,” said Richard D. Mattes, a professor of nutrition science at Purdue University.

Taste plays an intrinsic role as a chemical-sensing system for helping us find what is nutritious (stimulatory) and as a defense against what is poison (aversive). When we put food in our mouths, chemicals slip over taste buds planted into the tongue and palate. As they respond, we are thrilled or repulsed by what we’re eating.

But the body’s reaction may not always be a conscious one. In the late 1980s, in a windowless laboratory at Brooklyn College, the psychologist Anthony Sclafani was investigating the attractive power of sweets. His lab rats loved Polycose, a maltodextrin powder, even preferring it to sugar.

That was puzzling for two reasons: Maltodextrin is rarely found in plants that rats might feed on naturally, and when human subjects tried it, the stuff had no obvious taste.

More than a decade later, a team of exercise scientists discovered that maltodextrin improved athletic performance — even when the tasteless additive was swished around in the mouth and spit back out. Our tongues report nothing; our brains, it seems, sense the incoming energy.

“Maybe people have a taste for Polycose,” Dr. Sclafani said. “They just don’t recognize it consciously, which is quite an intriguing possibility.”

Dr. Sclafani and others are finding evidence that taste receptors on the tongue are also present throughout the intestine, perhaps serving as a kind of unconscious guide to our behavior. These receptors influence the release of hormones that help regulate food intake, and may offer new targets for diabetes treatments, Dr. Sclafani said.

Many tastes are consciously recognized, however, and they are distinguished by having dedicated sets of receptor cells. Fifteen years ago, molecular biologists began figuring out which of these cells in the mouth elicit bitter and sweet tastes.

By “knocking out” the genes that encode for sweet receptors, they produced mice that appeared less likely to lap from sweet-tasting bottles. Eventually, the putative receptors for salty and sour also were identified.

In 2002, though, as taste receptors were identified, the evidence largely confirmed the existence of one that scientist had been arguing about for years: savory.

Umami is subtle, but it is generally described as the rich, meaty taste associated with chicken broth, cured meats, fish, cheeses, mushrooms, cooked tomatoes and seaweed. Some experts believe it may have evolved as an imperfect surrogate for detecting protein.

Since then, researchers have proposed new receptor cells on the tongue for detecting calcium, water and carbonation. The growing list of putative tastes now includes soapiness, lysine, electric, alkaline, hydroxide and metallic.

“The taste field has been absolutely revolutionized,” said Michael Tordoff, a biologist at the Monell Chemical Senses Center. “We’ve made more progress in the last 15 years than in the previous 100.”

One candidate for the next basic taste appears to have emerged as the front-runner: fattiness. The idea has been around for a while, and many scientists thought it was not a specific taste, more like a texture or an aroma.

But researchers recently identified two taste receptors for unsaturated fats on the tongue. And fat evokes a physiological response, Dr. Mattes has found that blood levels of fat rise when we put dietary fat in our mouths, even without swallowing or digesting it.

Hours after a meal, the taste of fatty acids alone can elevate triglyceride levels, even when the nose is plugged. But fat, like umami, does not have a clear, perceptible sensation, and it is hard to distinguish a texture from a taste.

Dr. Mattes says that fat may have a texture that we like (rich and gooey) and a taste that we don’t (rancid).

If so, the taste may serve as part of our sensory alert system. When food spoils, he notes, it often contains high levels of fatty acids, and the taste of them may be “a warning signal.”

Although there is still no consensus beyond sweet, salty, sour, bitter and savory, the research makes clear there is more to taste than a handful of discrete sensations on the tongue. Before long, scientists may have to give up altogether on the idea that there are just a few basic tastes.

“If you’re talking three, four, five, six, you can still call it a pretty exclusive club,” Dr. Mattes said. “If you start getting beyond that, is the concept really useful?”

Nanoparticles may harm the brain
A simple change in electric charge may make the difference between someone getting the medicine they need and a trip to the emergency room—at least if a new study bears out. Researchers investigating the toxicity of particles designed to ferry drugs inside the body have found that carriers with a positive charge on their surface appear to cause damage if they reach the brain.
These particles, called micelles, are one type of a class of materials known as nanoparticles. By varying properties such as charge, composition, and attached surface molecules, researchers can design nanoparticles to deliver medicine to specific body regions and cell types—and even to carry medicine into cells. This ability allows drugs to directly target locations they would otherwise be unable to, such as the heart of tumors. Researchers are also looking at nanoparticles as a way to transport drugs across the blood-brain barrier, a wall of tightly connected cells that keeps most medication out of the brain. Just how safe nanoparticles in the brain are, however, remains unclear.
So Kristina Bram Knudsen, a toxicologist at the National Research Centre for the Working Environment in Copenhagen, and colleagues tested two types of micelles, which were made from different polymers that gave the micelles either a positive or negative surface charge. They injected both versions, empty of drugs, into the brains of rats, and 1 week later they checked for damage. Three out of the five rats injected with the positively charged micelles developed brain lesions. The rats injected with the negatively charged micelles or a saline control solution did not suffer any observable harm from the injections, the team will report in an upcoming issue of Nanotoxicology.
Knudsen speculates that one of the attributes that makes positive micelles and similar nanoparticles such powerful drug delivery systems may also be what is causing the brain damage. Because cells have a negative charge on their outside, they attract positively charged micelles and bring them into the cell. The micelles’ presence in the cell or alteration of the cell’s surface charge, she says, may disrupt the cell’s normal functioning.
Negatively charged nanoparticles can also enter cells, according to other research. However, they do so less readily and must be able to overcome the repulsion between themselves and the cell surface. It is possible that the reason the negatively charged micelles were not found to be toxic was that they did not invade cells to the same extent as the positively charged micelles. 
The findings are intriguing, says biomedical engineer Jordan Green of Johns Hopkins University in Baltimore, Maryland. But he cautions that there is no evidence that all positively charged nanoparticles behave this way. Other factors can also play a role in the toxicity of nanoparticles, adds pharmaceutical expert Jian-Qing Gao of Zhejiang University in Hangzhou, China. The size and concentration of the particles, as well as the strain of rat used, could all have influenced the results, he says.

Nanoparticles may harm the brain

A simple change in electric charge may make the difference between someone getting the medicine they need and a trip to the emergency room—at least if a new study bears out. Researchers investigating the toxicity of particles designed to ferry drugs inside the body have found that carriers with a positive charge on their surface appear to cause damage if they reach the brain.

These particles, called micelles, are one type of a class of materials known as nanoparticles. By varying properties such as charge, composition, and attached surface molecules, researchers can design nanoparticles to deliver medicine to specific body regions and cell types—and even to carry medicine into cells. This ability allows drugs to directly target locations they would otherwise be unable to, such as the heart of tumors. Researchers are also looking at nanoparticles as a way to transport drugs across the blood-brain barrier, a wall of tightly connected cells that keeps most medication out of the brain. Just how safe nanoparticles in the brain are, however, remains unclear.

So Kristina Bram Knudsen, a toxicologist at the National Research Centre for the Working Environment in Copenhagen, and colleagues tested two types of micelles, which were made from different polymers that gave the micelles either a positive or negative surface charge. They injected both versions, empty of drugs, into the brains of rats, and 1 week later they checked for damage. Three out of the five rats injected with the positively charged micelles developed brain lesions. The rats injected with the negatively charged micelles or a saline control solution did not suffer any observable harm from the injections, the team will report in an upcoming issue of Nanotoxicology.

Knudsen speculates that one of the attributes that makes positive micelles and similar nanoparticles such powerful drug delivery systems may also be what is causing the brain damage. Because cells have a negative charge on their outside, they attract positively charged micelles and bring them into the cell. The micelles’ presence in the cell or alteration of the cell’s surface charge, she says, may disrupt the cell’s normal functioning.

Negatively charged nanoparticles can also enter cells, according to other research. However, they do so less readily and must be able to overcome the repulsion between themselves and the cell surface. It is possible that the reason the negatively charged micelles were not found to be toxic was that they did not invade cells to the same extent as the positively charged micelles. 

The findings are intriguing, says biomedical engineer Jordan Green of Johns Hopkins University in Baltimore, Maryland. But he cautions that there is no evidence that all positively charged nanoparticles behave this way. Other factors can also play a role in the toxicity of nanoparticles, adds pharmaceutical expert Jian-Qing Gao of Zhejiang University in Hangzhou, China. The size and concentration of the particles, as well as the strain of rat used, could all have influenced the results, he says.

explore-blog:

Legendary neurologist Oliver Sacks, who is 81 today, on memory and the necessary forgettings of creativity 

explore-blog:

Legendary neurologist Oliver Sacks, who is 81 today, on memory and the necessary forgettings of creativity 

Secrets of the Creative Brain

A leading neuroscientist who has spent decades studying creativity shares her research on where genius comes from, whether it is dependent on high IQ—and why it is so often accompanied by mental illness. 

by Nancy Andreasen

 As a psychiatrist and neuroscientist who studies creativity, I’ve had the pleasure of working with many gifted and high-profile subjects over the years, but Kurt Vonnegut—dear, funny, eccentric, lovable, tormented Kurt Vonnegut—will always be one of my favorites. Kurt was a faculty member at the Iowa Writers’ Workshop in the 1960s, and participated in the first big study I did as a member of the university’s psychiatry department. I was examining the anecdotal link between creativity and mental illness, and Kurt was an excellent case study.

He was intermittently depressed, but that was only the beginning. His mother had suffered from depression and committed suicide on Mother’s Day, when Kurt was 21 and home on military leave during World War II. His son, Mark, was originally diagnosed with schizophrenia but may actually have bipolar disorder. (Mark, who is a practicing physician, recounts his experiences in two books, The Eden Express and Just Like Someone Without Mental Illness Only More So, in which he reveals that many family members struggled with psychiatric problems. “My mother, my cousins, and my sisters weren’t doing so great,” he writes. “We had eating disorders, co-dependency, outstanding warrants, drug and alcohol problems, dating and employment problems, and other ‘issues.’ ”)

While mental illness clearly runs in the Vonnegut family, so, I found, does creativity. Kurt’s father was a gifted architect, and his older brother Bernard was a talented physical chemist and inventor who possessed 28 patents. Mark is a writer, and both of Kurt’s daughters are visual artists. Kurt’s work, of course, needs no introduction.

For many of my subjects from that first study—all writers associated with the Iowa Writers’ Workshop—mental illness and creativity went hand in hand. This link is not surprising. The archetype of the mad genius dates back to at least classical times, when Aristotle noted, “Those who have been eminent in philosophy, politics, poetry, and the arts have all had tendencies toward melancholia.” This pattern is a recurring theme in Shakespeare’s plays, such as when Theseus, in A Midsummer Night’s Dream, observes, “The lunatic, the lover, and the poet / Are of imagination all compact.” John Dryden made a similar point in a heroic couplet: “Great wits are sure to madness near allied, / And thin partitions do their bounds divide.”

Compared with many of history’s creative luminaries, Vonnegut, who died of natural causes, got off relatively easy. Among those who ended up losing their battles with mental illness through suicide are Virginia Woolf, Ernest Hemingway, Vincent van Gogh, John Berryman, Hart Crane, Mark Rothko, Diane Arbus, Anne Sexton, and Arshile Gorky.

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What Happens If You Apply Electricity to the Brain of a Corpse?
Some habits die hard. Like humans zapping their brains. We did this back in Ancient Greece, when medics used electric fish to treat headaches and other ailments. Today we’re still at it, as neuroscientists apply electric currents to people’s brains to boost their mental function, treat depression, or give them lucid dreams.
Subjecting the brain to external electricity has an influence on mental function because our neurons communicate with each other using electricity and chemicals. This has become relatively common knowledge today, but only two centuries ago scientists were still quite baffled by the mystery of nerve communication.
Issac Newton and others suggested that our nerves communicate with each other, and with the muscles, via vibrations. Another suggestion of the time was that the nerves emit some kind of fluid. Most opaque, and still popular, was the idea – first mooted in ancient times – that the brain and nerves are filled with mysterious “animal spirits”.
“Animal electricity”
During the eighteenth century our understanding of electricity was growing apace, and the use of electricity to treat a range of physical and mental ailments, known as electrotherapy, was incredibly popular. But still it wasn’t obvious to scientists at the time that the human nervous system produces its own electric charge, and that the nerves communicate using electricity.
Among the first scientists to make this proposal was the Italian physician Luigi Galvani (1737-1798). Most of Galvani’s experiments were with frogs’ legs and nerves, and he was able to show that lightning or man-made electrical machines could cause the frogs’ muscles to twitch. He subsequently came up with the idea of “animal electricity” – that animals, humans included, have their own intrinsic electricity.
“I believe it has been sufficiently well established that there is present in animals an electricity which we … are wont to designate with the general term ‘animal’ … “ he wrote. “It is seen most clearly … in the muscles and nerves.”
Neuroscience’s macabre past
However, to Galvani’s frustration, he failed to show that zapping the brain had an effect on the facial or peripheral muscles. Here, he was helped in dramatic, macabre fashion by his nephew Giovanni Aldini (1762-1834).
In 1802, Aldini zapped the brain of a decapitated criminal by placing a metal wire into each ear and then flicking the switch on the attached rudimentary battery. “I initially observed strong contractions in all the muscles of the face, which were contorted so irregularly that they imitated the most hideous grimaces,” he wrote in his notes. “The action of the eylids was particularly marked, though less striking in the human head than in that of the ox.”
During this era, there was fierce scientific debate about the role of electricity in human and animal nervous systems. Galvani’s influential rival, Alessandro Volta, for one, did not believe in the notion that animals produce their own electricity. In this context, the rival camps engaged in public relations exercises to promote their own views. This played to Aldini’s strengths. Something of a showman, he took his macabre experiments on tour. In 1803, he performed a sensational public demonstration at the Royal College of Surgeons, London, using the dead body of Thomas Forster, a murderer recently executed by hanging at Newgate. Aldini inserted conducting rods into the deceased man’s mouth, ear, and anus.
One member of the large audience later observed: “On the first application of the process to the face, the jaw of the deceased criminal began to quiver, the adjoining muscles were horribly contorted, and one eye was actually opened. In the subsequent part of the process, the right hand was raised and clenched, and the legs and thighs were set in motion. It appeared to the uninformed part of the bystanders as if the wretched man was on the eve of being restored to life.”
Although Frankenstein author Mary Shelley was only five when this widely reported demonstration was performed, it’s obvious that she was inspired by contemporary scientific debates about electricity and the human body. Indeed, publication of her novel coincided with another dramatic public demonstration performed in 1818 in Glasgow by Andrew Ure, in which application of electric current to a corpse appeared to cause it to resume heavy breathing, and even to point its fingers at the audience.
Death is a process
If a body is dead, how come its nerves are still responsive to external electric charge? In 1818, one popular but mistaken suggestion was that electricity is the life force, and that the application of electricity to the dead could literally bring them back to life. Indeed, so disturbed were many members of the audience at Ure’s demonstration that they had to leave the building. One man reportedly fainted. Modern scientific understanding of the way nerves communicate undermines such supernatural interpretations, but you can imagine that witnessing such a spectacle as performed by Ure or Aldini would even today be extremely unnerving (excuse the pun). A pithy explanation of why electricity appears to animate a dead body comes courtesy of Frances Ashcroft’s wonderful book The Spark of Life:
“The cells of the body do not die when an animal (or person) breathes its last breath, which is why it is possible to transplant organs from one individual to another, and why blood transfusions work,” she writes. “Unless it is blown to smithereens, the death of a multicellular organism is rarely an instantaneous event, but instead a gradual closing down, an extinction by stages. Nerve and muscle cells continue to retain their hold on life for some time after the individual is dead and thus can be ‘animated’ by application of electricity.”
The grisly experiments of Aldini and Ure seem distasteful by today’s standards, but they were historically important, stimulating the imagination of novelists and scientists alike.

What Happens If You Apply Electricity to the Brain of a Corpse?

Some habits die hard. Like humans zapping their brains. We did this back in Ancient Greece, when medics used electric fish to treat headaches and other ailments. Today we’re still at it, as neuroscientists apply electric currents to people’s brains to boost their mental function, treat depression, or give them lucid dreams.

Subjecting the brain to external electricity has an influence on mental function because our neurons communicate with each other using electricity and chemicals. This has become relatively common knowledge today, but only two centuries ago scientists were still quite baffled by the mystery of nerve communication.

Issac Newton and others suggested that our nerves communicate with each other, and with the muscles, via vibrations. Another suggestion of the time was that the nerves emit some kind of fluid. Most opaque, and still popular, was the idea – first mooted in ancient times – that the brain and nerves are filled with mysterious “animal spirits”.

“Animal electricity”

During the eighteenth century our understanding of electricity was growing apace, and the use of electricity to treat a range of physical and mental ailments, known as electrotherapy, was incredibly popular. But still it wasn’t obvious to scientists at the time that the human nervous system produces its own electric charge, and that the nerves communicate using electricity.

Among the first scientists to make this proposal was the Italian physician Luigi Galvani (1737-1798). Most of Galvani’s experiments were with frogs’ legs and nerves, and he was able to show that lightning or man-made electrical machines could cause the frogs’ muscles to twitch. He subsequently came up with the idea of “animal electricity” – that animals, humans included, have their own intrinsic electricity.

“I believe it has been sufficiently well established that there is present in animals an electricity which we are wont to designate with the general term ‘animal’ “ he wrote. “It is seen most clearly in the muscles and nerves.”

Neuroscience’s macabre past

However, to Galvani’s frustration, he failed to show that zapping the brain had an effect on the facial or peripheral muscles. Here, he was helped in dramatic, macabre fashion by his nephew Giovanni Aldini (1762-1834).

In 1802, Aldini zapped the brain of a decapitated criminal by placing a metal wire into each ear and then flicking the switch on the attached rudimentary battery. “I initially observed strong contractions in all the muscles of the face, which were contorted so irregularly that they imitated the most hideous grimaces,” he wrote in his notes. “The action of the eylids was particularly marked, though less striking in the human head than in that of the ox.”

During this era, there was fierce scientific debate about the role of electricity in human and animal nervous systems. Galvani’s influential rival, Alessandro Volta, for one, did not believe in the notion that animals produce their own electricity. In this context, the rival camps engaged in public relations exercises to promote their own views. This played to Aldini’s strengths. Something of a showman, he took his macabre experiments on tour. In 1803, he performed a sensational public demonstration at the Royal College of Surgeons, London, using the dead body of Thomas Forster, a murderer recently executed by hanging at Newgate. Aldini inserted conducting rods into the deceased man’s mouth, ear, and anus.

One member of the large audience later observed: “On the first application of the process to the face, the jaw of the deceased criminal began to quiver, the adjoining muscles were horribly contorted, and one eye was actually opened. In the subsequent part of the process, the right hand was raised and clenched, and the legs and thighs were set in motion. It appeared to the uninformed part of the bystanders as if the wretched man was on the eve of being restored to life.”

Although Frankenstein author Mary Shelley was only five when this widely reported demonstration was performed, it’s obvious that she was inspired by contemporary scientific debates about electricity and the human body. Indeed, publication of her novel coincided with another dramatic public demonstration performed in 1818 in Glasgow by Andrew Ure, in which application of electric current to a corpse appeared to cause it to resume heavy breathing, and even to point its fingers at the audience.

Death is a process

If a body is dead, how come its nerves are still responsive to external electric charge? In 1818, one popular but mistaken suggestion was that electricity is the life force, and that the application of electricity to the dead could literally bring them back to life. Indeed, so disturbed were many members of the audience at Ure’s demonstration that they had to leave the building. One man reportedly fainted. Modern scientific understanding of the way nerves communicate undermines such supernatural interpretations, but you can imagine that witnessing such a spectacle as performed by Ure or Aldini would even today be extremely unnerving (excuse the pun). A pithy explanation of why electricity appears to animate a dead body comes courtesy of Frances Ashcroft’s wonderful book The Spark of Life:

“The cells of the body do not die when an animal (or person) breathes its last breath, which is why it is possible to transplant organs from one individual to another, and why blood transfusions work,” she writes. “Unless it is blown to smithereens, the death of a multicellular organism is rarely an instantaneous event, but instead a gradual closing down, an extinction by stages. Nerve and muscle cells continue to retain their hold on life for some time after the individual is dead and thus can be ‘animated’ by application of electricity.”

The grisly experiments of Aldini and Ure seem distasteful by today’s standards, but they were historically important, stimulating the imagination of novelists and scientists alike.

Is It Really True That Watching Porn Will Shrink Your Brain?
A hundred years ago they said that masturbating would make you go blind. We’ve progressed. Today, we’re told that watching moderate amounts of pornography will shrink your brain. The claim arrives courtesy of a brain imaging paper published last month in JAMA Psychiatry, a respected medical journal.
Among the global hyperbolic headlines that followed, one was from a German site: “Pea brain: watching porn online will wear out your brain and make it shrivel.” Others included “Viewing porn shrinks the brain” (from the reliably untrustworthy Daily Mail) and Watching Porn Linked To Less Gray Matter In The Brain (from Huffington Post).
The study that triggered all this concern was published by a German pair: Simone Kühn, a psychologist, and Jürgen Gallinat, a psychiatrist. They scanned the brains of 64 healthy men (average age 29) in three ways. Note the word healthy. In fact, all the men who participated were free from any psychiatric or neurological disorders. So if they had shrunken brains (we’ll come onto that later), it wasn’t causing them any major problems.
The first scan was a simple structural brain scan. The second looked at patterns of brain activation when the men viewed sexual or neutral images. The third scan looked at brain activity while the men relaxed in the scanner for five minutes (a so-called resting-state scan). The men also answered questions about how much porn they watch. They averaged four hours per week, and none of them met the criteria for Internet sex addiction according to the “Internet Sex Screening Test”.
Here’s what’s caused all the fuss. The researchers found that hours spent watching porn was negatively correlated with the amount of grey matter in a subcortical region near the front of the brain – the right striatum – that’s known to be involved in the processing of reward (as well as lots of other things). In other words, men who said they spent more time watching porn tended to have a smaller amount of grey matter in this part of their brain. Also, the more avid porn viewers showed less activation in their left striatum when they looked at racy images, and they appeared to have reduced connectivity between their right striatum and their left dorsolateral prefrontal cortex.
So, does watching porn shrink your brain? The researchers think it probably does. “One may be tempted,” they wrote “to assume that the frequent brain activation caused by pornography exposure might lead to wearing and down regulation of the underlying brain structure, as well as function …”.
One may be tempted, but one should really know better. The most glaringly obvious problem with this study is of course its cross-sectional methodology. It’s just as likely that men with less grey matter in their striatum are more attracted to porn, as opposed to porn causing that brain profile. The researchers know this. “It’s not clear … whether watching porn leads to brain changes or whether people born with certain brain types watch more porn,” Kühn told The Daily Telegraph (and yet that paper still ran the headline: “Watching pornography damages men’s brains”).
A further problem with correlational studies is not just that the causal direction can run either way, but that an unknown or uncontrolled third factor (and others) could be causally involved. In the case of this study, the elephant in the room is personality. Unsurprisingly, personality is linked with media use (including porn consumption) and with brain characteristics. Asking men how much porn they watch is a crude indicator of their extraversion, (lower) conscientiousness and desire for sensation seeking. For instance, men who watch porn in work hours tend to be less conscientious and more impulsive. Last year, a study reported: “Neuroticism, agreeableness, conscientiousness, and obsessional checking all significantly correlated with a latent measure of compulsive behavior upon which use of Internet pornography use also loaded.”
Amazingly, although Kühn and Gallinat checked their participants were free from depression and addiction, they otherwise failed to measure their participants’ personality traits. Had they done so, they would likely have found strong associations between personality and brain structure and function. Past research has already shown that high sensation seekers have reduced sensitivity to high arousal pictures (including nudity and gore). Other research has documented differences in resting-state brain activity according to personality. Still further research has shown how extraverts, and those more open to experience, are more persuaded by advertising that uses sexual imagery.
By failing to measure or control for personality, the results of this study are virtually meaningless. The men’s self-reported time spent watching porn is little more than a rough proxy for their personality profile, including their willingness to diverge details about their private habits. And we already know that key personality traits such as extraversion and sensation seeking are linked with distinct patterns of brain structure and response. By failing to follow up participants over time, the research also provides no evidence that watching porn has any effects whatsoever. Moreover, by also neglecting to measure any other media consumption, then even if before/after evidence were available, we wouldn’t know if it were due to porn consumption or to other media activities correlated with that porn use, such as watching violent movies and online gambling (to be fair, the findings did still hold after the researchers controlled for overall levels of internet use).
The researchers have witnessed newspapers spread headlines of brain shrinkage and brain harm, and yet they know that they specifically recruited psychologically and neurologically healthy men. In fact, therein lies the only really meaningful insight from this study. Look at it this way. In a survey of 64 men who answered recruitment adverts for a brain scanning study, it was found that they viewed an average of four hours porn a week. They do so with no apparent ill consequence – screening confirmed no psychiatric, medical or neurological problems. Of course there is a debate to be had about the merits and harms of porn for individuals and society. This study does not make a helpful contribution. Suggested new headline: “Watching moderate amounts of porn won’t hurt your brain”.

Is It Really True That Watching Porn Will Shrink Your Brain?

A hundred years ago they said that masturbating would make you go blind. We’ve progressed. Today, we’re told that watching moderate amounts of pornography will shrink your brain. The claim arrives courtesy of a brain imaging paper published last month in JAMA Psychiatry, a respected medical journal.

Among the global hyperbolic headlines that followed, one was from a German site: “Pea brain: watching porn online will wear out your brain and make it shrivel.” Others included “Viewing porn shrinks the brain” (from the reliably untrustworthy Daily Mail) and Watching Porn Linked To Less Gray Matter In The Brain (from Huffington Post).

The study that triggered all this concern was published by a German pair: Simone Kühn, a psychologist, and Jürgen Gallinat, a psychiatrist. They scanned the brains of 64 healthy men (average age 29) in three ways. Note the word healthy. In fact, all the men who participated were free from any psychiatric or neurological disorders. So if they had shrunken brains (we’ll come onto that later), it wasn’t causing them any major problems.

The first scan was a simple structural brain scan. The second looked at patterns of brain activation when the men viewed sexual or neutral images. The third scan looked at brain activity while the men relaxed in the scanner for five minutes (a so-called resting-state scan). The men also answered questions about how much porn they watch. They averaged four hours per week, and none of them met the criteria for Internet sex addiction according to the “Internet Sex Screening Test”.

Here’s what’s caused all the fuss. The researchers found that hours spent watching porn was negatively correlated with the amount of grey matter in a subcortical region near the front of the brain – the right striatum – that’s known to be involved in the processing of reward (as well as lots of other things). In other words, men who said they spent more time watching porn tended to have a smaller amount of grey matter in this part of their brain. Also, the more avid porn viewers showed less activation in their left striatum when they looked at racy images, and they appeared to have reduced connectivity between their right striatum and their left dorsolateral prefrontal cortex.

So, does watching porn shrink your brain? The researchers think it probably does. “One may be tempted,” they wrote “to assume that the frequent brain activation caused by pornography exposure might lead to wearing and down regulation of the underlying brain structure, as well as function …”.

One may be tempted, but one should really know better. The most glaringly obvious problem with this study is of course its cross-sectional methodology. It’s just as likely that men with less grey matter in their striatum are more attracted to porn, as opposed to porn causing that brain profile. The researchers know this. “It’s not clear … whether watching porn leads to brain changes or whether people born with certain brain types watch more porn,” Kühn told The Daily Telegraph (and yet that paper still ran the headline: “Watching pornography damages men’s brains”).

A further problem with correlational studies is not just that the causal direction can run either way, but that an unknown or uncontrolled third factor (and others) could be causally involved. In the case of this study, the elephant in the room is personality. Unsurprisingly, personality is linked with media use (including porn consumption) and with brain characteristics. Asking men how much porn they watch is a crude indicator of their extraversion, (lower) conscientiousness and desire for sensation seeking. For instance, men who watch porn in work hours tend to be less conscientious and more impulsive. Last year, a study reported: “Neuroticism, agreeableness, conscientiousness, and obsessional checking all significantly correlated with a latent measure of compulsive behavior upon which use of Internet pornography use also loaded.”

Amazingly, although Kühn and Gallinat checked their participants were free from depression and addiction, they otherwise failed to measure their participants’ personality traits. Had they done so, they would likely have found strong associations between personality and brain structure and function. Past research has already shown that high sensation seekers have reduced sensitivity to high arousal pictures (including nudity and gore). Other research has documented differences in resting-state brain activity according to personality. Still further research has shown how extraverts, and those more open to experience, are more persuaded by advertising that uses sexual imagery.

By failing to measure or control for personality, the results of this study are virtually meaningless. The men’s self-reported time spent watching porn is little more than a rough proxy for their personality profile, including their willingness to diverge details about their private habits. And we already know that key personality traits such as extraversion and sensation seeking are linked with distinct patterns of brain structure and response. By failing to follow up participants over time, the research also provides no evidence that watching porn has any effects whatsoever. Moreover, by also neglecting to measure any other media consumption, then even if before/after evidence were available, we wouldn’t know if it were due to porn consumption or to other media activities correlated with that porn use, such as watching violent movies and online gambling (to be fair, the findings did still hold after the researchers controlled for overall levels of internet use).

The researchers have witnessed newspapers spread headlines of brain shrinkage and brain harm, and yet they know that they specifically recruited psychologically and neurologically healthy men. In fact, therein lies the only really meaningful insight from this study. Look at it this way. In a survey of 64 men who answered recruitment adverts for a brain scanning study, it was found that they viewed an average of four hours porn a week. They do so with no apparent ill consequence – screening confirmed no psychiatric, medical or neurological problems. Of course there is a debate to be had about the merits and harms of porn for individuals and society. This study does not make a helpful contribution. Suggested new headline: “Watching moderate amounts of porn won’t hurt your brain”.

Neuroscience’s New Toolbox

With the invention of optogenetics and other technologies, researchers can investigate the source of emotions, memory, and consciousness for the first time.

What might be called the “make love, not war” branch of behavioral neuroscience began to take shape in (where else?) California several years ago, when researchers in David J. Anderson’s laboratory at Caltech decided to tackle the biology of aggression. They initiated the line of research by orchestrating the murine version of Fight Night: they goaded male mice into tangling with rival males and then, with painstaking molecular detective work, zeroed in on a smattering of cells in the hypothalamus that became active when the mice started to fight.

The hypothalamus is a small structure deep in the brain that, among other functions, coördinates sensory inputs—the appearance of a rival, for example—with instinctual behavioral responses. Back in the 1920s, Walter Hess of the University of Zurich (who would win a Nobel in 1949) had shown that if you stuck an electrode into the brain of a cat and electrically stimulated certain regions of the hypothalamus, you could turn a purring feline into a furry blur of aggression. Several interesting hypotheses tried to explain how and why that happened, but there was no way to test them. Like a lot of fundamental questions in brain science, the mystery of aggression didn’t go away over the past century—it just hit the usual empirical roadblocks. We had good questions but no technology to get at the answers.

By 2010, Anderson’s Caltech lab had begun to tease apart the underlying mechanisms and neural circuitry of aggression in their pugnacious mice. Armed with a series of new technologies that allowed them to focus on individual clumps of cells within brain regions, they stumbled onto a surprising anatomical discovery: the tiny part of the hypothalamus that seemed correlated with aggressive behavior was intertwined with the part associated with the impulse to mate. That small duchy of cells—the technical name is the ventromedial hypothalamus—turned out to be an assembly of roughly 5,000 neurons, all marbled together, some of them seemingly connected to copulating and others to fighting.

“There’s no such thing as a generic neuron,” says Anderson, who estimates that there may be up to 10,000 distinct classes of neurons in the brain. Even tiny regions of the brain contain a mixture, he says, and these neurons “often influence behavior in different, opposing directions.” In the case of the hypothalamus, some of the neurons seemed to become active during aggressive behavior, some of them during mating behavior, and a small subset—about 20 percent—during both fighting and mating.

That was a provocative discovery, but it was also a relic of old-style neuroscience. Being active was not the same as causing the behavior; it was just a correlation. How did the scientists know for sure what was triggering the behavior? Could they provoke a mouse to pick a fight simply by tickling a few cells in the hypothalamus?

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