What's the buzz: Microglia

There is growing evidence demonstrating that immune cells and signaling molecules serve as carriers in an intricate network of bidirectional communication between the immune system and the brain. This occurs via peripheral immune pathways as well as through interactions between neurons and the resident immune cells in the brain known as microglia. It turns out that microglia are involved in a lot more than just protecting the brain from infections; it has been shown that microglia are capable of influencing the growth and activity of neighbouring neurons. This affects the plastic nature of neuronal networks, and thus microglia are able to affect cognitive and social behaviors. 

In a recent study from Jonathan Kipnis' lab at University of Virginia, School of Medicine, researchers showed that restoring microglial function in a mouse model of Rett Syndrome, a severe autism-spectrum disorder that affects 1 in 10,000-20,000 girls worldwide. The disease is caused by a mutation in the gene MECP2, which is carried on the X chromosome. Since males carry only one copy of the X chromosome, males with the mutation die very soon after being born, whereas girls with one copy of the mutation develop the disease. 

Signs of the disease typically set in between 6 and 18 months of age. Affected females often have trouble developing speech, walking and putting on weight. Many patients also develop breathing problems and apnoeas. They also display repeated behaviors such as hand washing and wringing. 

MECP2 is an important epigenetic regulator, meaning it is able to regulate the expression of genes by recruiting enzymes that modify the structure of chromatin network. How exactly a mutation in the gene is sufficient to cause Rett Syndrome is still a mystery, but researchers have been able to detect its expression widely in the brain. In fact, rescuing MECP2 expression in neurons in Rett Syndrome mice reverses some of the disease phenotypes. More recently however, researchers lie Kipnis began to look for MECP2 function in other cell types in the brain, like microglia. It is now known that microglia indeed do express MECP2, so Kipnis and colleagues began to ask whether restoring MECP2 function in microglia in a Rett Syndrome mouse would improve the symptoms. 

The researchers accomplished this by essentially replacing the immune system of the mutant mouse lacking MECP2. They first had to kill of the existing immune system using radiation, and then used a bone marrow transplant from a healthy wildtype mouse to the mutant mouse; thus the new microglia in the Rett Syndrome mouse now have MECP2 in them. In an unexpected result, the restoration of MECP2 function in microglia resulted in drastic improvements in the mutant mice; they began to breathe and walk better, and even gain weight more easily compared to the non-transplanted mutant mice. 

These findings, while exciting, are very preliminary in terms of bone marrow transplants being used in human Rett Syndrome patients.  At this point, Kipnis speculates that their results could be explained by the fact that microglia in mutant Rett Syndrome animals are unable to clear up and protect the neurons from cellular waste build up and potential pathogens, and thus neuronal function is impaired. More research is required to identify the mechanism of microglia function in Rett Syndrome. However, the study does provide a novel role for microglia in the brain, and a new target for treatment of Rett Syndrome.

Remember to remember

As someone who is studying neuroscience, I come across the topic of memory very often. Finding out how memories are formed and stored is after all a major impetus that drives research in neuroscience. This Ted Talk by Josh Foer, a science journalist who writes for a number of publications including National Geographic and The New York Times, gives an interesting perspective on how we make memories. In 2005, Josh went to cover the U.S Memory Championship, a competition of mental sports in which participants have to memorize as much information as possible within a given amount of time. There he met many extraordinary people with extraordinary memories, or so he thought, until he began training with some of the participants and realized the strategies they used basically came down to creating a visual and spatial framework to place memories. Called a 'memory palace', this context within your mind's eye allows you to extract memories more easily. But Josh points out that, this strategy is in fact not novel; before the advent of technological tools, strategies like the 'memory palace' was an effective way to memorize speeches and even academic material for tests. We've just forgotten how to use it because we have other places to store the memory palace besides our brain: our computers, our smartphones, and for the really old school people, photo albums. In other words, we've forgotten how to make memories, and therefore how to remember. What really drives the point home is that, after a year of training with the top European memorizer, Josh entered in the national Memory Championship in New York- and won. Because he remembered to remember. 

Check the talk out at:

http://www.ted.com/talks/joshua_foer_feats_of_memory_anyone_can_do.html

Hmmm.....

 

After a two week hiatus, The Gray Area is back with a post describing a study that investigated how the feeling of suspicion is created in our brains. One of my first posts was about researchers have been trying to study how person's brain activity is altered when he/she is telling a lie vs. telling a truth, that is, the neural basis of deception. This current study attempts to describe how brain activity may change when we think someone might be telling a lie, that is, the neural basis for the feeling of suspicion. 

Using the same technique of fMRI, these scientists at Virginia Tech Carilion Research have identified two regions that may be involved in creating the feeling of suspicion- the amygdala and parahippocampal gyrus. The amygdala is involved in processing fear and emotional memories, while the parahippocampal gyrus plays a central role in declarative memory. The task was this: There were 76 pairs of participants, each with a buyer and a seller. Each pair competed in 60 rounds of a bargaining game, while having their brains scanned by the fMRI machine. At the start of each round, the buyer was told the value of a hypothetical widget, and then they were asked to suggest a price to the seller. The seller was then asked to set a selling price; if the seller's price fellow below the stipulated widget, the trade would go through, with the seller receiving the selling price and the buyer receiving any difference between the selling price and the stipulated value. However, if the seller's value exceeded the stipulated price, the trade would not go through, and neither the buyer or seller would receive cash. 

The researchers found that the buyers fell into three categories: 42% were incrementalists, meaning they were actually quite honest about the stipulated value; 37% were conservatives, meaning they tended to withhold information; 21% were strategists, who intentionally deceived the sellers by pretending to be incrementalists (making higher value suggestions when the stipulated value was low, and vice versa). The sellers did have the monetary incentive to correctly predict the stipulated value, but they had no feedback about the buyer's accuracy. The investigators found that the more uncertain the seller was about the buyer's suggested price, the more active his or her amygdala and parahippocampal gyrus became. The activation of the amygdala was not very surprising to the authors, as suspicion is an emotional state. But Read Montague, the lead investigator 

and director of the Human Neuroimaging Laboratory and the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute, says the activation of the parahippocampal gyrus could be "an inborn lie detector" or a reminder of an untrustworthy person. 

While this study is not a great replication of real life situations in which we may encounter suspicious behaviors or people, it may be important in understanding the neurological basis of increased suspicion and distrust in neuropsychiatric disorders such as anxiety disorders and paranoia.