Pain Receptor in Brain May Be Linked to Learning and Memory/Mice With Human Brain Cells Created/Angry people enjoy provoking others

March 14, 2008

Pain Receptor in Brain May Be Linked to Learning and Memory

http://www.scienceblog.com/cms/pain-receptor-brain-may-be-linked-learning-and-memory-15666.html

Scientists have long known that the nervous system receptor known as TRPV1 can affect sensations of pain in the body. Now a group of Brown University scientists has found that these receptors – a darling of drug developers – also may play a role in learning and memory in the brain.

In surprising new research, published in the journal Neuron, Julie Kauer and her team show that activation of TPRV1 receptors can trigger long-term depression, a phenomenon that creates lasting changes in the connections between neurons. These changes in the brain – and the related process of neural reorganization known as long-term potentiation – are believed to be the cellular basis for memory making.

“We’ve known that TRPV1 receptors are in the brain, but this is some of the first evidence of what they actually do there,” Kauer said. “And the functional role we uncovered is unexpected. No one has previously linked these pain receptors to a cellular mechanism underlying memory. So we may have found a whole new player in brain plasticity.”

The study findings have implications for drug development, Kauer said.

The research points out potentially effective new targets for drugs that could prevent memory loss or could possibly treat neural disorders such as epilepsy, Kauer said. The other implication may be cautionary. Drug makers already sell drugs – such as the weight-loss pill rimonabant, which is sold in Europe under the name Acomplia – that can block TRPV1 receptors. Other drugs aimed at reducing pain and inflammation by blocking or activating TRPV1 receptors are in the research pipeline. But drugs that bind to TRPV1 receptors in the central nervous system are likely to influence more than just pain-related functions, Kauer said.

“Our findings suggest the possibility that some of the psychiatric side effects from rimonabant could be due to the blocking of TRPV1 receptors,” she said.

TRPV1, short for transient receptor potential vanilloid subtype, can be found all over the nervous system, including in skin, the spinal cord and the brain. These receptors can sense heat, trigger inflammation and transmit pain. TRPV1 receptors not only respond to heat but also to capsaicin, the compound that creates the spicy kick in chili peppers.

In her study, Kauer, professor of medical science in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown, treated rat brain tissue from the hippocampus, the brain’s seat of learning and memory, with capsaicin. The team found that this compound activated TRPV1 channels – which alone triggered long-term depression in the brain tissue. Further, rimonabant entirely blocked long-term depression by blocking TRPV1 channels.

The team then tested brain tissue from mice that lacked TRPV1 receptors and found that long-term depression was absent – and that applying capsaicin still couldn’t elicit the changes to the synapses.

Kauer’s Brown research team includes postdoctoral research associate Helen Gibson, undergraduate student Rachel Page, and graduate student Matthew Van Hook. Jeffrey Edwards, a former postdoctoral research associate and current neuroscience professor at Brigham Young University, also contributed to the work.

The National Institutes of Health funded the work.

http://www.brown.edu/

Mice With Human Brain Cells Created

http://news.nationalgeographic.com/news/2005/12/1214_051214_stem_cell.html

Brian Handwerkfor National Geographic News

December 14, 2005

Researchers in California have created living mice with functioning human stem cells in their brains. The feat could boost stem cell therapy research on brain diseases like Parkinson's and Alzheimer's—and raises the specter of animal-human hybrids.

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Geneticist Fred Gage injected embryonic human cells into two-week-old fetal mice as they developed in the womb. When the mice matured, some human stem cells survived and became functional components of the mice's brains and nervous systems. Less than one-tenth of one percent of the test mice's brain cells are human. "When we characterized these cells two months later, we found that [they] had the [form and structure] and characteristics of mouse cells," said Gage, co-director of the genetics laboratory at the Salk Institute for Biological Studies in San Diego. "It is truly amazing that these human stem cells, although they are very immature, can still … respond to different cues in their environment and can fit right in with their mouse neighbors.This illustrates that injecting human stem cells into mouse brains doesn't restructure the brain," Gage added. The study was published in yesterday's issue of the journal Proceedings of the National Academy of Sciences. Medical Promise or Ethical Peril? Some scientists hope that stem cells, which may develop into many different kinds of human cells, could someday be used to replace missing or damaged neurons in people with degenerative nerve diseases. "This research is significant because it suggests that it will be possible to create mouse 'models' of human brain tissue, enabling scientists to try out both stem cell interventions and other potential cures on living human brain cells without having to use humans in the process," said Glenn McGee, director of the Alden March Bioethics Institute at Albany Medical College in New York State. In short, it's a new way to test potential cures for human diseases, without harming human test subjects in the process.

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http://www.scienceblog.com/cms/angry-people-enjoy-provoking-others-12866.html

Most people don't appreciate an angry look, but a new University of Michigan psychology study found that some people find angry expressions so rewarding that they will readily learn ways to encourage them.

"It's kind of striking that an angry facial expression is consciously valued as a very negative signal by almost everyone, yet at a non-conscious level can be like a tasty morsel that some people will vigorously work for," said Oliver Schultheiss, co-author of the study and a U-M associate professor of psychology.

The findings may explain why some people like to tease each other so much, he added.

"Perhaps teasers are reinforced by that fleeting 'annoyed look' on someone else's face and therefore will continue to heckle that person to get that look again and again," he said. "As long as it does not stay there for long, it's not perceived as a threat, but as a reward."

U-M psychology researchers Michelle Wirth and Schultheiss, the authors of the study, published their findings in the journal Physiology and Behavior. They took saliva samples from participants to measure testosterone, a hormone that has been associated with dominance motivation.

Participants then worked on a "learning task" in which one complex sequence of keypresses was followed by an angry face on the screen, another sequence was followed by a neutral face, and a third sequence was followed by no face.

Participants who were high in testosterone relative to other members of their sex learned the sequence that was followed by an angry face better than the other sequences, while participants low in testosterone did not show this learning advantage for sequences that were reinforced by an angry face.

Notably, this effect emerged more strongly in response to faces that were presented subliminally, that is, too fast to allow conscious identification. Perhaps just as noteworthy, participants were not aware of the patterns in the sequences of keypresses as they learned them.

While high-testosterone participants showed better learning in response to anger faces, they were unaware of the fact that they learned anything in the first place and unaware of what kind of faces had reinforced their learning.

Wirth, the lead author of the study and now a postdoctoral researcher at the University of Wisconsin, Madison, added: "Better learning of a task associated with anger faces indicates that the anger faces were rewarding, as in a rat that learns to press a lever in order to receive a tasty treat. In that sense, anger faces seemed to be rewarding for high-testosterone people, but aversive for low-testosterone people."

She said the findings contribute to a body of research suggesting that perceived emotional facial expressions are important signals to help guide human behavior, even if people are not aware that they do so.

"The human brain may have built-in mechanisms to detect and respond to emotions perceived in others," she said. "However, what an emotional facial expression, such as anger, 'means' to a given individual—whether it is something to pursue or avoid, for example—can vary."

Source University of Michigan