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Showing entries tagged optogenetics.  Show all entries

December 4, 2011

The Joy of Laughter


Laughter. Its something we humans do almost on a daily basis in order to express pleasure yet it is composed of a series of grimaces and loud shrieks. How is it that such a strong, blissful emotion can be connected with such obtuse behaviors? Furthermore where does this feeling of joy come from? The scientists at Stanford say they have it all figured out.

In the December 4 2003 issue of Neuron a study done by the Stanford University School of Medicine asserted that laughter and humor activate the mesolimbic dopaminergic reward system. In this study sixteen adult subjects viewed 42 funny and 42 non-funny cartoons in a random order and were asked to press a button depending on if they found the cartoon funny or not. Prior to the experiment a separate group of subjects with a background similar to the test group chose 42 of the funniest cartoons from a selection of 130 cartoons. 42 non-funny cartoons were then found to match these.

In order to find the areas of the brain that were active when a cartoon was presented to the subject an event related fMRI (efMRI) was used. The areas were determined active if there was an increase in blood flow in that region of the brain. The unpredictable nature of random efMRI designs, the fact that activation was examined on a subject-by-subject and cartoon-by-cartoon basis, an the use of post scan humor ratings ensured that pure reward was being measured while consideration and measurement of individual differences in humor were taken into a account.

The researchers discovered that the regions activated included the ventral tegmentum area, nucleus accumbens, and amygdala, all which are vital to the mesolimbic dopaminergic reward system. Other areas such as the supplementary motor area, dorsal anterior cingulate cortex, and inferior frontal gyrus (including Broca's area) were also activated in the left hemisphere which suggests that this hemisphere plays a large role in the processing of reward and positive emotional stimuli. It also suggests that this hemisphere is responsible for the physical display of humor such as smiling and laughter.

Thus when we laugh, we do so because of the release of dopamine which causes the feel good feeling and stimulates the necessary areas that cause the actual behavior of laughing. Dopamine also keeps us laughing due to the reward system it employs.

These discoveries make it is possible to further studies on the use of laughter as medicine. One possible way to study if laughter has beneficial effects is through the use of optogenetics. By activating the areas discovered here with optogenetics, it would be possible to measure the effects laughter has on the immune and cardiovascular systems. It would also be possible to see if laughter could be used to effectively treat forms of depression that are due to a lack of dopamine release within the brain. Another, more necessary study using optogenetics would be to simply test if these areas alone account for humor or if it is the combination of the areas that make something appear funny. By doing these tests it would be possible to see if laughter really is the best medicine or if it is simply a social construction that promotes good feelings.

Citation:

http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=272195&_user=10&_pii=S0896627303007517&_check=y&_coverDate=2003-12-04&view=c&_gw=y&wchp=dGLzVlS-zSkzV&_valck=1&md5=2af750b3e08a955b3e8f9c81abfaadc2&ie=/sdarticle.pdf
Posted by      Mari W. at 4:31 PM MST

July 30, 2011

A Clockwork Character: Molding the Mozg


It is not hard to imagine a futuristic dystopian society. Constructing dystopias seems to be one of the main methods by which those of a sci-fi persuasion can offer poignant social commentary. However, some of these dystopias are far more horrific than others. One would be hard pressed to find a dystopia more controversial than the one presented in Stanley Kubrick's A Clockwork Orange (adapted from Anthony Burgess's novel of the same name); watching Alex DeLarge and his small gang of droogs terrorize futuristic Britain with "ultra-violence" is more than enough to make your insides squirm in revulsion. In perhaps the film's most infamous scene, Alex and his droogs beat a man so severely as to cripple him for life, and then proceed to rape his wife - all while happily singing "Singin' in the Rain". And yet there's hope for this futuristic Britain, a way to clean ultra-violence from the streets by rehabilitating those delinquent youths like Alex: an experimental aversion therapy called the Ludovico technique. If you were in charge of such a dystopia as the one depicted in A Clockwork Orange, where the fabric of society was being viciously ripped apart by rampant ultra-violence, wouldn't you be desperate for a way to stop it? And rather than just locking up criminals and social delinquents, wouldn't it be better if you could help those individuals by eradicating their anti-social behavior? Wouldn't this allow your dystopia to rapidly evolve into a utopia?

For those familiar with the film, we know that it's not just the use of ultra-violence that makes the film so controversial. Controversy also lies in the film's social commentary on morality and behavioral psychology, which is far too deep and expansive of a discussion for the scopes of this post. However, A Clockwork Orange does raise an interesting question (in fact, it raises many interesting questions): how close are scientists to understanding human behavior? Are they close enough to know which parts of the brain are responsible for certain behaviors? Are they close enough to actually control behavior?

The answer: yes. Scientists can switch social behaviors on and off as easily as flicking a light switch, at least in mice.

In an effort to understand what causes social-behavior deficits in humans, particularly those with social disorders like autism and schizophrenia, researchers from Stanford University are using pulses of light to toggle social behaviors on and off in mice. Led by Dr. Karl Deisseroth, researchers used optogenetics to test an established yet untested hypothesis about social dysfunction: that "elevation of in the ratio of cortical cellular excitation to inhibition (cellular E/I balance), for example through increased activity in excitatory neurons or reduction in inhibitory neuron function, could give rise to the social and cognitive deficits observed in diseases such as autism" (Yizhar et al, Nature, 2011). So, "when facing social stimulus people with social disorders experience an imbalance wherein too many excitatory nerves fire (or not enough inhibitory nerves fire) resulting in a kind of over-responsiveness" (Dillow, Popular Science). In order to test this theory, scientists used optogenetics to bioengineer excitatory and inhibitory nerve cells in the parts of the brain responsible for social function to fire on command. Specifically, the researchers looked at excitatory and inhibitory nerve cells in the medial prefrontal cortex, which is involved in processes such as planning, execution, personality and social behavior. When compared to normal mice, the experimental mice exhibited no difference in their anxiety levels, their tendency to move around, or their curiosity about new objects. However, the experimental mice whose medial prefrontal cortex excitability had been optogenetically stimulated lost all interest in engaging with other mice. Their social behavior was largely abolished. Further, the brains of these mice showed the same gamma-oscillation pattern that is observed among many autistic and schizophrenic patients, meaning that this study could have implications in getting to the root of the behavior seen in those with social deficits, like those with autism. It's possible that this research could provide valuable information for finding a treatment for behavioral disorders like autism and schizophrenia.

Researchers at CalTech, too, have been altering mouse behavior. They have located the brain's trigger for aggression, a cluster of cells in the ventromedial hypothalamus (VMH), an area that previous studies have associated with sexual behavior. It's not so surprising that aggressive and sexual behavior stem from the same area of the brain (at least, it's not so surprising when considered in the context of A Clockwork Orange); they come from intermingled yet separate clusters of neurons in the VMH. By identifying these clusters of neurons in the VMH, scientists found that aggression is triggered by a specific tangle of neurons, which they could turn on and off in mice by using light (after making the region photosensitive via a process of inserting custom-made viruses carrying a modified piece of DNA into the brain). When the nerve cluster was excited, no matter what they put in the cage with the experimental mouse, the mouse would attack - be it another male mouse, a female mouse, or even a dummy mouse. The opposite also held true; when the nerve cluster was silenced, the experimental mouse was completely non-aggressive, even in the presence of a threatening male. And, because mice have cognitive function and physiology that is quite similar to ours, then perhaps aggression in humans, too, could be toggled on and off like a light switch.

These findings could have quite the positive potential for us humans. Not only does it allow us to better understand our own minds, but it could offer cures for behavioral disorders like autism and schizophrenia. And in the future, who knows? Maybe scientists will discover switches for other behavioral problems as well, such as anxiety or phobias or OCD or ADHD.

And yet, we shouldn't ignore the warnings provided to us through (albeit potentially paranoid) social commentary. Though A Clockwork Orange offers an extreme example of behavioral modification, it is still an example of behavioral modification nonetheless, and a real possibility of what could happen if scientific advancements are taken out of control and used to pursue corrupt political agendas. On what A Clockwork Orange is all about, Kubrick said the following: that it is "a social satire dealing with the question of whether behavioral psychology and psychological conditioning are dangerous new weapons for a totalitarian government to use to impose vast controls on its citizens and turn them into little more than robots." Again, extreme. We shouldn't live in a paranoid static state of fear that every scientific discovery made could lend itself to ultimately crippling humanity in some manner. The pursuit of knowledge should not be hindered by fear or ignorance; finding cures for behavioral disorders like autism and schizophrenia would be ultimately beneficial, and would help many people live better, more fulfilling lives. However, it should always by the obligation of the scientist to make sure that the truths they discover are not somehow corrupted to advance personal agendas, and to make sure that they educate the public as to their discoveries. To combine the words of Francis Bacon and Spider-man: knowledge is power, and with great power comes great responsibility.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10360.html
http://www.popsci.com/science/article/2011-07/scientists-switch-social-behaviors-and-mice-shedding-light-human-social-disorders
http://www.popsci.com/science/article/2011-07/caltech-researchers-find-switch-mouse-and-perhaps-human-aggression
Posted by      Caitlin W. at 6:37 PM MDT




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