Image by Ben Emery

Immature oligodendrocyte cells from mice, growing in a Petri dish, in the process of maturing. Only mature oligodendrocytes produce myelin in the brain. The magenta and green stains represent proteins found in myelin, the insulating sheath that helps neurons conduct electricity.

When it comes to science, there is more cooperation than rivalry. Australian scientist Ben Emery worked with American colleagues at Stanford and discovered a gene that is required for cells in the brain to produce myelin, the insulating sheath that allows neurons to function properly.

Emery grew up in Kyneton, Australia. Interested in aquatic life, he planned to study marine biology, but a psychology course at the University of Melbourne got him hooked on neuroscience. He remained in Melbourne for his Ph.D., studying how chemicals from the immune system affect the survival of oligodendrocytes, the cells in the brain that form myelin.

Image by Jennifer Zamanian

Ben Emery

Emery’s wife is a physician; she had just completed her first year of post-medical school training when they moved to California. Because of the difficulty using her Australian medical degree to practice medicine in the United States (she would need to take licensing exams and repeat part of her training), she has put her career on hold for the past four years.

This makes being far from home particularly difficult.

The absence of family locally is keenly apparent since the birth of their daughter late last year. According to Emery, in Australia it is common to attend university close to home, but geographic separation from family seems more common and routine in the United States.

But all this sacrifice appears to have paid off for Emery’s career. He recently discovered a gene that tells oligodendrocytes to form myelin.

Immature oligodendrocytes are not capable of forming myelin. But as the brain matures a series of genes turns on in the immature oligodendrocytes, causing the cells to mature. The mature oligodendrocytes then alter the composition of their cell membranes and wrap around neurons, forming an insulating sheath known as myelin. Scientists have identified genes that trigger an immature oligodendrocyte to mature, but the genes that trigger a mature oligodendrocyte to form myelin were unknown until Emery’s discovery.

By comparing the genes that are turned on in immature and mature oligodendrocytes from mice, Emery and his colleagues identified a gene that is turned on at very high levels in mature oligodendrocytes but is on at very low levels in immature cells. The gene, which Emery named myelin regulatory factor, is not turned on in other cells in the brain, such as neurons.

Emery then genetically engineered mice to lack myelin regulatory factor in oligodendrocytes. Immature oligodendrocytes matured but failed to form myelin (the mice died at 3 weeks old). When Emery forced the myelin regulatory factor gene to turn on in oligodendrocytes growing in a Petri dish, the cells began producing proteins required for myelin.

Based on its similarity to other genes, it’s likely that the myelin regulatory factor gene produces a protein that activates other genes. Emery speculates that myelin regulatory factor acts as a master regulator of myelin, turning on the genes that allow the oligodendrocyte to form myelin. But Emery is quick to point out that turning on the myelin regulatory factor in a kidney cell does not cause that cell to form myelin - there must be other factors at work as well.

Emery proved that myelin regulatory factor is required for myelin formation in the brain when an animal is growing and developing. Now the question is whether this factor is required when myelin forms in adults. So called re-myelination occurs after injury, but is compromised in diseases such as multiple sclerosis. Emery is working to answer this; meanwhile another group found that the myelin regulatory factor gene is turned on in regions of the human brain that contain lots of myelin.

Emery’s discovery landed him two job offers: one at a university in the United States, one at a university in Australia. Other than family considerations, he does not feel compelled to return to Australia to practice science. “You can contribute [to science] wherever you wind up.”

Source: “Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination” by Ben Emery, Dritan Agalliu, John D. Cahoy, Trent A. Watkins, Jason C. Dugas, Sara B. Mulinyawe, Adilijan Ibrahim, Keith L. Ligon, David H. Rowitch and Ben A. Barres, published in Cell, July 10, 2009.

Surgeons performing deep brain stimulation surgery.

When it comes to understanding how the brain processes information, scientists started big: we know which parts of the brain are activated during vision, hearing and other senses, and in many cases, such as vision, we know how the brain organizes the information at the level of individual brain cells (called neurons).

More recent work has focused on delving deeper into brain function, attempting to understand which neurons are activated during more complex behaviors, such as learning from rewarding experiences.

Now a recent paper provides evidence that cells in the substantia nigra, a region deep within the brain, are important for responding to the unexpected.

There are several techniques scientists use to monitor brain activity, but one of the most direct is to place electrodes inside the brain and record when neurons produce electrical impulses. Neurons communicate by producing an electrical impulse that is transmitted to neighboring cells. The strength, frequency and location of these impulses - which neurons are ‘firing,’ and when - varies, and that is how the brain interprets and responds to stimulation.

For decades scientists have studied this process in nonhuman primates, like monkeys and chimpanzees, by placing electrodes inside the brain and recording which neurons fire during a specific activity.

Performing similar experiments in humans is difficult, since nobody wants a hole drilled into their skull and an electrode implanted into their brain.

Nobody healthy, that is. Recording electrical activity from human brains is standard practice during neurosurgery, when the brain is exposed. Scientists are sometimes able to take advantage of the situation and perform brief experiments with minimal risk to the patient that don’t affect the surgery.

Recording electrical activity from a conscious, human brain is a “unique opportunity” to contribute to our basic understanding of brain function, Kareem Zaghloul told me.

Zaghloul and his colleagues at the University of Pennsylvania in Philadelphia performed an experiment on patients with Parkinson’s disease undergoing deep brain stimulation surgery. Once the patient’s brains were exposed, Zaghloul inserted electrodes to record from the substantia nigra and had the patients play a card game on a computer screen for five minutes. Patients could pick a card from either a red or a blue deck and were informed that cards from one deck were more likely to yield a virtual financial reward (a stack of gold coins appears on the screen with an audible ring and a counter showing accumulated earnings). Scientists rigged the game so that 65 percent of the cards from one deck and 35 percent of the cards from the other deck yielded a financial reward. (If drawing a card did not yield a virtual reward, the screen turned blank with an audible buzz.)

After several rounds, the 65/35 ratio allowed patients to figure out which deck was more likely to yield a reward, but still allowed patients’ expectations to be thrown off occasionally. If patients expected the chosen deck to yield a reward and it did (an expected gain) or if patients expected the chosen deck to yield no reward and it did (an expected loss), neurons in the substantia nigra fired at similar rates. But when patients expected a deck to yield nothing but instead received a reward (an unexpected gain), neurons fired more frequently than in the opposite situation (an unexpected loss).

This is the first time that higher firing rates after unexpected gains have been demonstrated in humans, and validates similar results from studies in nonhuman primates - reinforcing the value of animal models. But Zaghloul’s study is also a proof-of-principle, showing that it’s possible to record neural activity directly while subjects are performing complicated tasks that can’t be performed by chimpanzees. Zaghloul and his colleague’s results are improving our understanding of how humans learn from rewarding experiences.

Source: “Human Substania Nigra Neurons Encode Unexpected Financial Rewards” by Kareem A. Zaghloul, Justin A. Blanco, Christoph T. Weidemann, Kathryn McGill, Jurg L. Jaggi, Gordon H. Baltuch and Michael J. Kahana, published in the March 13, 2009 issue of Science.

On April 22, the world’s oldest living Nobel laureate turned 100.

Italian biologist Rita Levi-Montalcini won the Nobel Prize in Medicine in 1986 for her discovery of nerve growth factor, a protein that triggers many types of nerves to grow.

Levi-Montalcini’s background is remarkable. As a Jew in fascist Italy in 1936, she was forced to leave her university. She took her experiments home with her – literally – and continued to study how animals develop at a makeshift laboratory in her house. From her autobiography:

In 1936 Mussolini issued the “Manifesto per la Difesa della Razza”, signed by ten Italian ’scientists’. The manifesto was soon followed by the promulgation of laws barring academic and professional careers to non-Aryan Italian citizens. After a short period spent in Brussels as a guest of a neurological institute, I returned to Turin on the verge of the invasion of Belgium by the German army, Spring 1940, to join my family. The two alternatives left then to us were either to emigrate to the United States, or to pursue some activity that needed neither support nor connection with the outside Aryan world where we lived. My family chose this second alternative. I then decided to build a small research unit at home and installed it in my bedroom.

After the end of World War II, she came to the United States to work with Viktor Hamburger at Washington University in St. Louis, where she made her seminal discovery.  She worked in St. Louis until 1977, when she retired to Italy.

In her case, retirement means working in the lab, helping her foundation support science fellowships for women in Africa and serving as a senator for life in the Italian government and as a goodwill ambassador of the Food and Agriculture Organization of the United Nations.

According to the Associated Press, she dispensed the following advice at her 100th birthday party:

“Above all, don’t fear difficult moments. The best comes from them.”

 
Globe-trotting biologist Kaoru Saijo began graduate studies in her native Japan, continued in Germany and finished in New York. Now in San Diego, her latest results provide a new link between inflammation and neurodegenerative diseases like Parkinson’s.

Kaoru received her medical degree from the Tokyo Medical and Dental University, but her passion for research led her to graduate school at Chiba University - at the time, combined M.D. and Ph.D. programs were uncommon in Japan. She happened to attend an immunology conference featuring German scientist Klaus Rajewsky, who brought along two of his students from the University of Cologne, one of whom fell in love with Kaoru. So in 1997 Kaoru moved to Cologne and continued her graduate research with Alexander Tarakhovsky, a group leader in Rajewsky’s lab.

Three years later Tarakhovsky got a job leading his own lab at the Rockefeller University in New York, so Kaoru and her husband moved to New York where she finally finished her Ph.D. research. (Rajewsky has since moved to Harvard.)

For those of you keeping score, that’s a Ph.D. from Chiba University.

Her husband then got a job in San Diego, so Kaoru followed.

Why not return to Japan? The environment is not “well equipped” for female scientists, Kaoru told me. Plus it’s difficult for a non-Japanese scientist to run a lab in Japan (Kaoru’s husband is German). According to Kaoru, the U.S. government supports foreign scientists very well.

In San Diego, Kaoru joined Christopher Glass’s laboratory to study how cells in the immune system work, which unexpectedly led her to Parkinson’s disease.

She and her colleagues were looking for genes in macrophages (a type of immune cell in the blood) that reduce inflammation and found that a gene named Nurr1 turns off other genes that produce an inflammatory response.

Meanwhile, Wei-dong Le and Pingyi Xu and their colleagues discovered in 2003 that mutations in Nurr1 are associated with rare cases of Parkinson’s disease, a condition in which neurons in the brain that produce dopamine deteriorate and die. Nurr1 helps control production of dopamine in neurons, and in mice missing Nurr1 researchers found a drastic reduction in the number of dopamine neurons. (We don’t know what causes most cases of the disease, which often does not run in families).

Science is all about making connections, and Kaoru cleverly observed that if Nurr1 has anti-inflammatory effects in blood cells, and Parkinson’s can be caused by improperly functioning Nurr1, then Nurr1 could be protecting the brain from inflammation - inflammation which is damaging the brain in Parkinson’s.

Kaoru’s colleague Beate Winner injected a dopamine-rich area of mouse brains with LPS, a component of bacteria that triggers inflammation. (See photo.) Dopamine neurons died - this normally takes two or three weeks. But when Beate injected LPS and a virus that turns off Nurr1, more dopamine neurons died very quickly, within one week.

Nurr1 is clearly preventing inflammation, but in which cells? Nurr1 is turned on in neurons, but it’s also turned on in microglial cells and in astrocytes, cells in the brain that are important for normal brain function. Microglial cells in the brain are thought to behave as macrophages do in the blood, defending tissue from foreign attack.

The virus that turns off Nurr1 preferentially infects astrocytes and microglia, not neurons, meaning that turning off Nurr1 in these cells, not in neurons, increased inflammation.

In other words, Nurr1 produced in microglial cells and astrocytes protects neurons from inflammation.

Scientists are finding evidence that inflammation is involved in a number of brain diseases, including Alzheimer’s disease and multiple sclerosis. Kaoru is now looking to see if Nurr1 plays a role in these diseases, and whether chemicals that activate Nurr1 could be used to treat disease.

Kaoru wants to stay in the United States and plans to apply for a faculty position here. While she misses her family in Japan, they understand her situation.

Source: “A Nurr1/CoREST Pathway in Microglia and Astrocytes Protects Dopaminergic Neurons from Inflammation-Induced Death” by Kaoru Saijo, Beate Winner, Christian T. Carson, Jana G. Collier, Leah Boyer, Michael G. Rosenfeld, Fred H. Gage and Christopher K. Glass, published on April 3 in Cell.

New media and social networking are all the rage these days: blogs, facebook, and now twitter, the free service that allows users to send 140 character messages via mobile texting, instant message or the Web.

The Israeli government even used twitter to hold a press conference (the toughest Q’s answered in the briefest tweets, wrote the New York Times.)

A recent study by Antonio Damasio and colleagues suggests that rapid, superficial information does not provide people time to feel admiration or compassion. Morality takes time.

Jenny Hope, of the United Kingdom’s Daily Mail, writes “although normal life events provide opportunities to feel admiration and compassion, researchers fear heavy social networkers may not have time for traditional ways of developing a moral sense such as reading books or seeing friends.”

Does that mean that reading books and seeing friends help make you moral?

Source: “Neural correlates of admiration and compassion” by Mary Helen Immordino-Yang, Andrea McColl, Hanna Damasio and Antonio Damasio, published in PNAS online April 20 (doi: 10.1073/pnas.0810363106).

Scientists are human, believe it or not, and sometimes we get so lost in the details that we fail to appreciate the fundamentals.

In diseases where myelin, the fatty insulation surrounding nerves, is destroyed, the working assumption is that restoring myelin will reverse symptoms of the disease — yet this basic premise never has been proven.

In demyelinating diseases such as multiple sclerosis, the body repairs some of its damaged myelin, and there is partial recovery of neurologic function, but it’s unclear how much of the recovery is due to the repaired myelin. Demyelination is accompanied by inflammation, so reducing inflammation could be the primary path to recovery. There is evidence that nerves might adapt to better conduct electrical impulses when myelin is damaged. The brain also might compensate for damaged circuitry by relying more on undamaged pathways.

This assumption is critical: if restoring myelin restores function, then scientists should focus their efforts on restoring myelin; if restoring myelin fails to restore function, then scientists should pursue a different strategy to treat demyelinating diseases.

Ian Duncan and colleagues at the University of Wisconsin recently showed that remyelination restores function in cats suffering from a unique demyelinating disease. Pregnant cats, fed a diet of irradiated food for months, developed severe neurological symptoms such as paralysis and vision loss. (Nobody knows why this happens to pregnant cats; a similar diet does not cause problems in rodents.)

These cats had widespread demyelination of the brain and spinal cord (but not peripheral nerves). Putting the cats back on a normal diet restored myelin, and the nerves remained intact. The myelin did not repair itself completely – in most areas the restored myelin was thinner than normal, but this seemed to be sufficient, because the cats recovered neurological function.

These results are tantalizing, because “it absolutely confirms the notion that remyelinating strategies are clinically important,” Duncan said in a statement.

As for the cats, many questions remain. How does the irradiated diet specifically target myelin, sparing the nerves (is the radiation destroying an essential vitamin, leading to deficiency)? What is unique about pregnant cats, making them susceptible? How does the immune system respond?

Source: “Extensive remyelination of the CNS leads to functional recovery” by I. D. Duncan, A. Brower, Y. Kondo, J. F. Curlee, Jr. and R. D. Schultz, published in PNAS online on April 2 (doi: 10.1073/pnas.0812500106).

Western music – the classical music that originated in Europe and has since spread and spawned jazz and rock ‘n roll – is frequently meant to express emotions.

I feel sad listening to ‘On the Transmigration of Souls’ by John Adams, happy listening to ‘My Favorite Things’ performed by John Coltrane.

Even in cases where I listen to Western music and I don’t feel the intended emotion, I can usually guess what emotion the composer is trying to evoke.

(I feel bored listening to most Western music written before 1900, but this is not usually the emotional response intended by the composer.)

Musicians are fond of saying that their art is universal, but does Western music evoke the intended emotional response from non-Western listeners?

This is a difficult question to answer – radio has spread music to nearly all areas of the world. Recently, a team of scientists from Canada, the UK and Germany, led by Thomas Fritz, began to answer this question by identifying people in a remote area of West Africa who have never been exposed to Western music.

The people are Mafa, one of approximately 250 ethnic groups in Cameroon, located in the northern Mandara mountains. Some Mafa communities lack electricity. Many residents pursue a traditional lifestyle and have never been exposed to Western music.

Fritz asked 21 Mafas, 37 to 90 years old, to listen to a series of 15 second computer-generated piano pieces, designed to “express the emotions happy, sad, and scared/fearful according to Western conventions” of tempo, pitch, rhythm, scale and melody. The Mafas, who don’t speak English or German, indicated their emotional response by pointing to one of three photographs of the same human face looking happy, sad or afraid.

Mafa participants recognized the happy music about 60% of the time, significantly more than the 30% you’d expect by chance. They correctly recognized the sad or fearful music about 50% of the time. (As you might expect, twenty German adults identified the correct emotions more than 80% of the time.)

What was surprising was that Westerners and Mafas seem to be responding to the same musical cues. Higher tempo was more likely to be associated with happy, lower tempo with fear; major key with happy, minor key with fear.

In a second experiment, Fritz played two versions of Mafa or Western music. One version was unmodified, the other was made more dissonant by playing it synchronously with the same tune a half-step higher and a tritone lower (imagine hearing the same melody sung by three people simultaneously in three different keys).

Mafas and Westerners described the original versions of their native and foreign music as more pleasant than the modified versions.

Bruce Bower, writing in ScienceNews, describes Mafa music as expressing joy and happiness exclusively. “Village revelers blow fervently through flutes made of iron, clay and wax at various rituals, including a harvest event. No word exists in the Mafa language for music, which is viewed as an inseparable element of ritual.”

Source: “Universal Recognition of Three Basic Emotions in Music” by Thomas Fritz, Sebastian Jentschke, Nathalie Gosselin, Daniela Sammler, Isabelle Peretz, Robert Turner, Angela D. Friederici and Stefan Koelsch, published online March 19 in Current Biology (doi:10.1016/j.cub.2009.02.058).

Leopoldo Petreanu and his colleagues have discovered a new method of mapping connections within the brain, a method that will drastically improve our understanding of how the brain works and could provide insight into how connections are disrupted in neurological disease.

Understanding how the brain works requires understanding how brain cells called neurons communicate. An electrical impulse travels along a neuron and triggers the release of a chemical. That chemical travels across the tiny gap between neurons, touches a second neuron and triggers another electrical impulse, which travels along the neuron, triggers release of a chemical, and so on.

Reaching out from the neuron are extensions called axons that conduct electrical impulses and release chemical messengers from their tips. On the other side are dendrites, branching projections poised to receive the chemical messengers, trigger an electrical impulse and send it toward the cell’s axon.

Dendrite branching is so extensive that scientists refer to it as the “dendritic arbor.” (Dendron is the Greek word for tree.)

The tiny gaps between axon and dendrite, which serve as communication points between neurons, are called synapses. Scientists have long sought to map the network of synapses present in the brain.

For a century, mapping synapses relied on staining neurons with a dye and assuming a synapse exists wherever the tips of neurons overlap. But recent work has shown that overlapping tips of axons and dendrites don’t always communicate. There’s not necessarily a synapse between all neighboring neurons.

It’s like trying to understand how people interact at a party by looking at a photograph. You might assume that a group of people standing close together are communicating with one another, and that somebody on the other side of the room is not part of that conversation.

That’s a logical assumption, but you wouldn’t know from the picture when only one person in the group is listening.

Petreanu and his colleagues devised a way to identify synapses on dendritic arbors by eavesdropping on their conversations. The new method marries two techniques: decades-old electrophysiology, which allows scientists to place an electrode into discrete areas of the brain and record electrical activity; and a light-sensitive protein that controls neural activity.

Illuminate a neuron and this light-sensitive protein causes axons to release chemical messengers across the synapse. On the dendrite side of the synapse, the electrode impaled in the cell’s body measures when a particular dendritic branch triggers an electrical impulse. This allowed Leopoldo to shine a light on the tip of an axon (the speaker), and identify the corresponding branch of the dendrite that responded with an electrical impulse (the listener). If a dendrite branch wasn’t listening, there would be no electrical impulse.

Leopoldo examined brain slices from mice and focused on part of the cerebral cortex, the outermost area of the brain. With the electrode in place recording from a single neuron, he moved a light all around - whenever the light identified a synapse, the electrode would record the impulse. By combining this technique with fluorescent proteins and dyes that label neurons, Leopoldo could trace axons and dendrites and identify the portion of the dendritic arbor where a synapse occurs.

In this initial report, Leopoldo mapped connections among dozens of types of neurons, but using this method scientists could potentially map thousands of neuronal connections throughout the brain - identify neurons that actually communicate, rather than those that appear to communicate because they are close together - leading to a new atlas of the brain.

Mapping functional synapses using this method requires sophisticated and expensive equipment, one reason why Leopoldo is here in the United States, where he has access to more resources than in his native Argentina. After graduating from the University of Buenos Aires, he came to New York for graduate studies at the Rockefeller University and is now a postdoctoral fellow at the Howard Hughes Medical Institute’s Janelia Farm research campus in Ashburn, Virginia.

Leopoldo wants to lead a lab at a university, and though he would like to return to Argentina he admits that resources for his cutting-edge research are better in the United States. His girlfriend is also a postdoc at Janelia Farm. Finding jobs at universities in the same city will be tough - which is why Leopoldo told me he is “not in a position to say no to anything,” even sacrificing resources for scientific equipment in order to live in the same city as his girlfriend.

Source: “The subcellular organization of neocortical excitatory connections” by Leopoldo Petreanu, Tianyi Mao, Scott M. Sternson and Karel Svoboda, published in the February 26 issue of Nature (doi:10.1038/nature07709).

The scientific community is buzzing now that President Obama has lifted the ban on federal funding for human embryonic stem cell research. In his announcement, the president was careful not to overstate the therapeutic promise of stem cells, but other sources, including some news outlets, have been less cautious. I’m going to follow up on that point by discussing a recent study published in PLoS Medicine that shows just how little we know about using human embryonic stem cells to treat disease.

Ataxia telangiectasia is a devastating and rare genetic disease with no cure, marked by difficulty walking and controlling one’s limbs, impaired eye movements, slurred speech and immune deficiencies. Patients usually die by their early twenties. Many symptoms are due to cells dying in the cerebellum, the part of the brain that coordinates movement. One idea is that stem cells from the brains of human embryos could replace the dying cells in the cerebellum of patients with ataxia telangiectasia.

In May 2001, a 9-year-old boy with ataxia telangiectasia was taken to Russia for the first of three injections of stem cells from fetal brain cells. In February 2005, the boy, suffering from recurring headaches, was examined by neurologists at Sheba Medical Center in Israel. MRI scans showed lesions at the base of the brain (near the cerebellum) and in the spinal cord. The latter tumor was surgically removed. Analysis of the DNA from tumor cells and the patient’s blood cells indicated that the tumor cells did not originate in the patient. The tumor cells must have grown from the transplanted stem cells. (Many tumor cells possessed two X chromosomes, indicating that they are female, but the patient is male.)

This study might teach us something about brain tumors. One theory is that stem cells acquire mutations that lead to unchecked growth; this small population of cells multiplies and forms a tumor. The results of this study suggest it is possible that brain tumors could come from stem cells. Of course, these were stem cells from fetuses implanted into a diseased brain – treating the fetal stem cells with growth hormones before injection could have triggered them to form tumors. Another possibility is that stem cells from fetal brains are more predisposed to unrestricted growth than other types of stem cells, or that the brain of a 9-year-old with ataxia telangiectasia is an environment more conducive to tumor growth than a normal juvenile or adult brain.

Clearly more research is needed to understand how stem cells grow.

Injecting this boy with stem cells does not appear to have been conducted as part of a clinical trial with multiple participants and rigorous follow up. Detailed methods describing how the fetal cells were grown and analyzed in dishes before injection were not published. From the methods that were provided to the Israeli researchers who analyzed the tumor, “cells of various size and form” were used, suggesting that many different types of fetal brain cells were injected into the boy.

I’ll leave the authors with the final word:

“Conventional therapies such as chemotherapy, radiotherapy, and bone marrow transplantation used to treat life threatening diseases are associated with morbidity and mortality. Our findings therefore do not imply that the research in stem cell therapeutics should be abandoned. They do, however, suggest that extensive research into the biology of stem cells and in-depth preclinical studies, especially of safety, should be pursued in order to maximize the potential benefits of regenerative medicine while minimizing the risks.”

Is the promise of stem cell therapy exaggerated? How much preclinical study is required before a therapy should be tested in humans?

Source: “Donor-Derived Brain Tumor Following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient” by Ninette Amariglio, Abraham Hirshberg, Bernd W. Scheithauer, Yoram Cohen, Ron Loewenthal, Luba Trakhtenbrot, Nurit Paz, Maya Koren-Michowitz, Dalia Waldman, Leonor Leider-Trejo, Amos Toren, Shlomi Constantini, Gideon Rechavi, published in the February 2009 issue of PLoS Medicine (doi:10.1371/journal.pmed.1000029)

Four years ago young neuroscientist Karl Deisseroth developed a light-sensitive protein that could be used to control neural activity. When you shine a light on the neuron, the protein opens and allows ions to enter the neuron, which triggers a signal that travels to neighboring neurons. Since then Deisseroth and others have modified these light-sensitive proteins (light can also be used to prevent neural activity) and used them to analyze how neurons communicate during different behaviors in mice.

Now Ofer Yizhar, an Israeli postdoctoral researcher in Deisseroth’s lab, has helped develop a way to turn on neural activity with a brief pulse of light, and keep it on until a second brief pulse shuts it off. Ofer’s paper demonstrates that this light-activated on/off switch works in neurons grown in a petri dish. (See photo.) When scientists use genetic tricks to introduce this switch into the brains of living mice, it will become a powerful tool with which to manipulate behavior.

Ofer grew up near Rehovot, Israel, and went to high school in Jerusalem. After serving his mandatory military service as an army press photographer and working for a year as a professional photographer for a news agency, Ofer studied at Hebrew University and received his doctorate in neuroscience from Tel Aviv University.

In Israel, it’s customary for scientists to go abroad for their postdoctoral fellowships, Ofer told me. Why the United States? There Ofer has access to scientists from all over the world, making it easy to interact with scientists from prominent labs. Getting scientists to lecture in the United States is easy; getting scientists to visit Israel is more difficult because of perceived security issues.

And then there’s money. The annual budget of Uri Ashery’s lab, where Ofer did his graduate work, is roughly equivalent to the monthly budget in Deisseroth’s lab – despite the fact that Ashery has been running a lab four years longer than Deisseroth. Moreover, due to bureaucracy it takes months for expensive equipment to be delivered to labs in Israel, compared with days in the United States.

Despite this, Ofer plans to return to Israel after his fellowship and try to get a job as an assistant professor. The quality of graduate students and scientists in Israel is good, and you are free to study whatever you want – it just takes longer. Ofer plans to develop tools (like light-activated neural switches) during his fellowship in the United States and then use them to study neural circuits in Israel.

The choice to return home is also personal. Ofer and his wife, also Israeli, want their kids to grow up near extended family. The cost of living is higher in the United States than in Israel, especially in the area of Northern California where Ofer works. And while the hiking at nearby Yosemite and Big Sur is incomparable, Ofer still yearns for his native land.

“After every visit home I feel clearly that I belong in Israel.”

“Bi-stable neural state switches” by André Berndt, Ofer Yizhar, Lisa A. Gunyadin, Peter Hegemann and Karl Deisseroth, published in the February 2009 issue of Nature Neuroscience.