Findings

by Greg Miller

As I watched a man two rows ahead of me sniffle and cough throughout a Tuesday afternoon symposium, I found myself worrying about his future mental health. After all, I'd just heard talk after talk about how immune system signaling molecules--like those triggered by infections--can muck with the brain and cause memory deficits and mood alterations.

Granted, much of this work was done with rodents. Staci Bilbo of Duke University in Durham, North Carolina, described evidence from her group suggesting that neonatal rats infected with Escherichia coli bacteria grow up to be poor performers in a standard test of rat memory. As adults, these animals have abnormally high numbers of activated microglial cells--the immune system's foot soldiers in the brain--in the hippocampus, a key memory center. Blocking microglia activation, Bilbo reported at the meeting, restores normal learning and memory.

Ruth Barrientos of the University of Colorado, Boulder, described findings from similar experiments with aging rats, suggesting that the very old as well as the very young may be particularly vulnerable to memory deficits triggered by infections and the resulting immune system activity.

Perhaps the most disturbing demonstration of the immune system's potential to influence the brain and behavior was a set of movies played by Judy Van de Water of the University of California, Davis. Van de Water is a co-investigator on a large study looking for environmental and genetic risk factors for autism. She and her colleagues have found that some mothers of autistic children have antibodies against proteins in the fetal brain. To investigate whether these antibodies could be interfering with fetal brain development, the researchers purified antibodies from human mothers of autistic children and injected them into gestating monkeys.

The movies showed the behavior of two such monkeys as adolescents. When put in a cage with another, familiar monkey, they didn't interact and play like monkeys normally do. One repeatedly ran back and forth across the floor of the enclosure. The other did backflips over and over in a corner. Although the findings are suggestive, Van de Water noted that only about 17% of moms of autistic kids in their cohort have tested positive for antibodies against fetal brain proteins. "It's certainly not what causes all autism," she said.

The most direct link to human mental health came from psychiatrist Andrew Miller of Emory University in Atlanta, who described his work with cancer patients taking immune system activating drugs to fight cancer. In 2001, Miller and colleagues reported that nearly half of people who take one such drug, interferon alfa-2b, become depressed within 12 weeks. At the meeting, Miller presented brain-imaging data suggesting that people taking interferon alfa have abnormal metabolism in several brain regions important for regulating arousal and mood. "For us in psychiatry, the idea that infection and the immune system might come into play in disorders of the brain is one of the most exciting new ideas to come down the pike in some time," Miller said.

by Emily Laut

CREDIT: Wikimedia Foundation

The Wikipedia entry for "neuroscience" looks all right at first glance, but after attending a session on Monday, I knew otherwise. Two enthusiastic scientists turned Wikipedia Academy volunteers, Bill Wedemeyer and Tim Vickers, explained that Wikipedia articles get grades for completeness and readability and that the "neuroscience" article earns only a middling grade. I later visited the entry's discussion page and learned that editors feel it's incomplete, missing the history of neuroscience and exposition on topics such as neurosurgery and methods. Many other entries about neuroscience could use a boost, too; "neurogenetics" is summarized in a single "stub" paragraph, earning what amounts to a failing grade.

The Society for Neuroscience (SfN) thinks Wikipedia neuroscience ought to be better and has called for its members to edit Wikipedia, working on the premise that the more the public knows about neuroscience, the more votes and dollar support they'll throw behind research and the more bright people will want to work in the field. Vickers said that as the Internet's seventh most visited site and most people's first stop for information, Wikipedia is a public outreach powerhouse. He noted that in the days after news broke about the H1N1 influenza virus outbreak earlier this year, the H1N1 Wikipedia entry had 1.3 million readers a day. With so large a readership, Vickers argues, it's important for neuroscience on Wikipedia to be complete and accurate. Wedemeyer said scientists have a calling--even an ethical obligation--to share their knowledge.

But even if editing Wikipedia is the right thing to do, scientists may have good reasons for not wanting to get involved. Neuroscientist Chris Lossin of UC Davis pointed out that editing a Wikipedia article is time-consuming, and young scientists need to spend their time publishing articles for their tenure files.  And until there's a way to give scientists legitimate credit for their work, editing Wikipedia may seem like charity. (Also see this post on the Drug Monkey blog for an account of one scientist's frustrations with Wikipedia editing.)

Even so, many of the 30 or so attendees came specifically to learn to become active neuroscience Wikipedians. Anyone who missed it and wants to learn more can visit the sites for the Wikipedia Academy, the SfN Wikipedia Initiative, and an independent project called WikiProject Neuroscience, led by neuroscientist and Wikipedian Bill Skaggs, who also spoke at the session.

CREDIT: J. T. Dimos et al., Science, 29 August 2008, p. 1218

by Greg Miller

If you've been reading science news stories for the past couple of years, you've probably heard that induced pluripotent stem (iPS) cells are the next big thing. They have many of the same talents as embryonic stem cells, but they don't carry the ethical baggage. That's because iPS cells don't require the destruction of embryos: They can be created by reprogramming skin or other cells from any adult--including patients with nervous system disorders. Although iPS cells may one day be used as treatments, right now many researchers are using them primarily as research tools. This morning I stopped by a session on iPS cells to get a sense of how things are progressing.

Allison Ebert of the University of Wisconsin, Madison, gave a nice overview of a flurry of recent papers demonstrating the use of iPS cells derived from neurological patients. The first was a 2008 Science paper that used skin cells taken from an 82-year-old woman with amyotrophic lateral sclerosis to create iPS cells and coax them to differentiate into motor neurons. Earlier this year, Ebert and colleagues reported in Nature that they'd derived iPS cells and created motor neurons from a patient with another neuromuscular disorder, spinal motor ataxia (SMA). She and her colleagues are studying these cells for clues about why motor neurons die off in SMA. One early hint, she reported, is that genes involved in apoptosis, or programmed cell death, seem to be upregulated in these cells.

Ricardo Dolmetsch of Stanford spoke about his group's efforts to create iPS cells from patients with a variety of autism-related disorders and examine the resulting neurons for abnormalities in gene expression, fine-scale anatomy, and electrophysiology. Jason Chiang, a fifth-year graduate student at Johns Hopkins University, described his work with iPS cells from two people with trisomy 13, a profoundly debilitating neurodevelopmental disorder for which there is no good animal model. Chiang presented evidence that defects in cell signaling pathways involving Wnt proteins, key regulators of neural development, may be involved in the neurological aspects of the disorder.

Dolmetsch summed up the state of the field at the end of his talk, throwing up a slide from a tech consulting firm that traces (in a slightly tongue-in-cheek fashion) the stages of a new technology as it progresses from the "peak of inflated expectations" to the "trough of disillusionment" to the "slope of enlightenment," finally arriving at the "plateau of productivity." Dolmetsch used a laser pointer to indicate where he sees the field: just beginning to come down from the peak.

That seems about right. Despite the great potential iPS cells hold for unraveling the biology of neuropsychiatric disorders and testing potential treatments, many serious questions remain, not the least is how well the findings will translate to real patients. As Dolmetsch said: "I hope the trough isn't too deep."

CREDIT: CLIFF RAGSDALE AND SHUICHI SHIGENO

by Greg Miller

Did you know that an octopus brain has more than 50 lobes and about as many neurons (100 million) as a mouse's brain? And that's not counting the smaller brains in each arm and the tiny brains (okay, ganglia) devoted to each sucker? Neither did I, until I spent the morning visiting with Cliff Ragsdale and his postdoc Shuichi Shigeno at the University of Chicago.

Ragsdale and Shigeno think octopuses may have much to teach us about brain evolution. In size and complexity, the octopus brain rivals that of many vertebrate species. But it's put together much, much differently. "This is as far from the vertebrate design as we can get in a successful, living animal," Ragsdale says.

That raises interesting questions about whether the neural circuits that control movement, memory, and other functions in an octopus brain work the same way as do the analogous circuits in other animals. To investigate, Shigeno has been using molecular methods to examine the anatomy, neurochemistry, and developmental genetics of the octopus brain. He presented some of his preliminary findings yesterday at the Society for Neuroscience meeting in Chicago, and I'll post a longer discussion of this work (and more cool photos) later this week over on our Origins blog. Stay tuned.

by Greg Miller

Before this afternoon's social issues roundtable, I blithely assumed that neuroscience is mostly a good thing for society. It's all about understanding emotions, memory and cognition--the things that make us who we are--and tackling scourges such as Alzheimer's disease and depression. So I was thrown a bit off-guard by the opening remarks of the session moderator, Alan Leshner. "I think when the rest of society finds out what the broader implications of neuroscience research are, they're not going to like it," Leshner said.

(Full disclosure: Leshner is the CEO of the American Association for the Advancement of Science and executive publisher of Science, but I wasn't coerced, bribed, or even asked to show up at the roundtable or write about it.)

The other speakers picked up this troubling thread and highlighted aspects of neuroscience research that have the potential to elicit unease in the general population. Philosopher Patricia Churchland of the University of California, San Diego, spoke about the implications of research on the neural mechanisms of decision-making (which tend to sound pretty deterministic) for the widely held view that people must be held responsible for their actions. Cognitive neuroscientist Barbara Sahakian of the University of Cambridge, U.K., cited recent evidence that the use of cognitive-enhancing drugs such as modafinil is increasing among teenagers, raising questions about long-term effects on the still-developing adolescent brain, among other ethical worries. And philosopher Jonathan Moreno of the University of Pennsylvania flew through a history of military uses and abuses of psychology and neuroscience research, ranging from 1950s work on using LSD to pry secrets from enemy spies to current interest in using the "trust hormone" oxytocin to loosen lips.

Just when it seemed things could get no worse, Hank Greely of Stanford Law School pointed to several areas of potential friction between neuroscience research and widely held religious beliefs (findings that point to consciousness, or a form of it, in nonhuman animals, for example, might undermine the notion that humans occupy a unique position in the world) and asked whether neuroscientists might get dragged into the type of culture war waged by evolutionary biologists and creationists.

Greely went on to say that although he thinks that's possible, neuroscience is probably less likely to become a flash point in the culture wars than evolutionary science has been. To avoid that possibility, he said, neuroscientists should basically just be polite. "Don't offend people and inflame public passions," he said. "Don't overclaim and say you've proven there's no soul." (That sounds like good advice on several levels.)

But Churchland wasn't prepared to put courteousness above all else in the name of social harmony. Citing the public debates over abortion and right-to-die issues, she said that she's all for being polite until other people try to impose their own beliefs on her life: "Sometimes when my welfare is at stake I'm not as polite as I could be."

CREDIT: FENG ZHANG AND KARL DEISSEROTH

by Greg Miller

Optogenetics continues to be a hot topic. This emerging set of research tools combines genetic engineering and sophisticated optics to image or stimulate neural activity. The neural circuits that mediate things like mood, memory, and behavior are assembled from different types of cells--and optogenetics gives researchers a way to manipulate one cell type at a time to figure out what role it plays in the circuit.

Three posters presented this afternoon at the Society for Neuroscience meeting in Chicago illustrate how researchers interested in a wide range of questions are putting these methods to use. All three used the same basic strategy: injecting a virus into the brain region of interest to introduce a gene encoding a light-activated ion channel called channelrhodopsin-2 (ChR2). When neurons express ChR2, pulses of laser light delivered by an optical fiber open the channels and stimulate the neurons to fire.

Antoine Adamantidis of Stanford University in Palo Alto, California, has been using this approach to investigate neurons in the hypothalamus that influence the sleep-wake cycle. In previous work, he and colleagues used methods borrowed from genetic engineering to target ChR2 to only hypothalamic neurons that express the neuropeptide hypocretin. In a 2007 Nature paper, they reported that stimulating these hypocretin cells with laser pulses promoted wakefulness in mice. At the meeting, Adamantidis reported that stimulating a different type of hypothalamic neuron seems to have the opposite effect. When he and co-workers stimulated neurons that express melanin-concentrating hormone, a neuropeptide only recently linked to sleep regulation, mice slept more. The findings suggest that the two cell types have a push-pull effect on the sleep-wake cycle, Adamantidis says. But because they are such close neighbors in the hypothalamus, he says, it would have been impossible to tease them apart using conventional methods.

Meanwhile, Herbert Covington and colleagues at Mount Sinai School of Medicine in New York City have been using optogenetic methods to study a mouse model of depression. Mice that spend time with an aggressive bully (mouse) become withdrawn and avoid social contact even with friendly mice--an effect that's reversed by antidepressant drugs. Covington and colleagues used ChR2 to confer light sensitivity on neurons in the medial prefrontal cortex (mPFC), a brain region that's underactive in humans with depression, and then used laser pulses to stimulate neural activity. "Depressed" mice that got this treatment were less socially withdrawn, judging by the amount of time they spent interacting with a nonhostile stranger. In this case, Covington says the advantage of using optogenetics was the fast time resolution of the laser, which allowed the researchers to recreate patterns of neural activity that closely mimic those seen in the mPFC of presumably nondepressed mice freely exploring their enclosure.

Finally, Mary Kay Lobo of Mount Sinai presented findings suggesting that stimulation of different subtypes of cells in the nucleus accumbens, a key node in the brain's reward circuitry, can enhance or inhibit the rewarding effects of cocaine in mice. These cells express different versions of the receptor for the neurotransmitter dopamine and have different connections to other brain regions. Lobo has more experiments planned to investigate how they might be involved in drug use and addiction.

Although the findings are all preliminary, these studies (and others, such as this recent paper on memory) seem to suggest that these flashy methods are beginning to live up to their promise.

by Greg Miller (@dosmonos)

Apparently not even the 16,000-plus scientific presentations at this year's Society for Neuroscience (SfN) meeting are enough to fully occupy some of the 29,500 (and counting) attendees. Many are finding time to post short snippets on Twitter (hashtag #sfn09) about posters to check out, how to download meeting info onto an iPhone or other mobile device (see here or here), what beer is on tap at local restaurants, or how to get good wireless and cell phone reception in the convention center (good luck with that).

Blogging activity has picked up too this year. For the first time, SfN officially appointed 11 bloggers to cover various subtopics at the meeting, but they are not the only ones. Drug Monkey blog is keeping a list of both sanctioned and renegade bloggers in case you need something to do.