NRSC 4132 Blog

Raw sugar. Where did it go? I don't remember the last time I actually saw one-hundred percent, real, authentic sugar on the table the last time I was seated at a restaurant. Whether it's an iced tea, coffee or whatever I'm ordering that doesn't arrive at the table sweet enough to my liking, the only quick option I have is to choose one, or many, of those artificial sweetener packets located within arms reach. One might view one of those many companies who put so much time and money into making these packets so readily available at nearly every restaurant, a small additive solution to America's obesity issue that I discussed last week. Do you want sweet and low? Equal? How about Splenda? Or maybe even Truvia. Regardless, they're all fake. And for the most part, they all satisfy our need to make not only beverages, but confections and whatever else, taste more sweet.

The molecular mechanisms involved with sweet taste and the impact of artificial sweeteners are still not completely mapped out. Before I get into some of the interesting findings in the July 11' edition of The Journal of Neuroscience, let me give you a piece of advice: next time you reach for that white ceramic square containing all those fun colors of artificial sweeteners, stop yourself before you do and ask for some real sugar--it's in your best interest.

Taste qualities can be broken down into five major categories; sweet, bitter, sour, salty, and umami. Thus far, it has clearly been identified that the family C G-protein coupled receptor Tas1R2 and Tas1R3 heterodimer mediates the primary sensory transmission process of sweet taste perception. This receptor can be stimulated by many of these diverse natural or synthetic sweet ligands and proteins.

In Bo Liu et al.'s research involving artificial sweeteners, he and his team heterogeneously expressed and functionally assessed these receptors from a squirrel monkey which belongs to the genus Samimiri of New World monkeys. Using receptor chimeras between humans and squirrel monkeys, species-dependent sweet taste differences were determined by a combination of a few specific interaction sites on the Tas1R2 and Tas1R3 receptors. Using two primary ingredients to some (aspartame and neotame), but not all, artificial sweeteners, they found that Old World monkeys but not New World monkeys are able to taste the sweet sensation of such products. In their analysis of such results it was noted that specific residues, are required to taste something sweet and that the extracellular domain of the human Tas1R2 receptor is a critical site and contains important molecular determinants for activation by aspartame and neotame. Old World monkeys (and rats) had a hydrophobic binding site on these receptors which no longer exists on the New World species.

Though Liu et al. did not go on to mention any further experimentation or draw parallels for the human population, considering their BLAST search between the primates and human samples used was a strong 89% correlation some inferences can be made. To what extent evolution of New World monkeys and rats plays a part in this de-sensitization remains unknown, however, what happened to those specific species that hasn't happened to Homo sapiens yet? Regardless of whether or not we're going to potentially lose the ability to percept aspartame and neotame in the future, artificial sweeteners are already known to be bad for human homeostasis. Even though products such as Splenda (Sucralose) and Truvia claim to be all natural and aren't involved in this research, in large quantities, artificial sweeteners can be carcinogenic and in some studies have shown to actually cause weight gain. Considering the vast research boycotting the use of such products, I think it's best to say that we should just stick to the old fashioned way of making our drinks sweeter--with pure sugar cane. Whether you like it raw or not, your sugar cane that is, it just seems to be the smarter option.

When I was a kid I spent a lot of time trying to get my mom and dad to play board games with me. Unfortunately, most of these games required three or more players, and while Mom was usually a willing participant, Dad never relished the idea of spending an hour playing Clue or Candlyland with me. I never really got the hint, and to this day my closet at home is stuffed with board games that were taken out of the box once, set up neatly for three players, and then packed up and stuffed back in the closet without a single card drawn or the dice rolled once. It seems like some researcher may have shared my difficulty and was unable to find a single person to take part in that classic 1980s board game Guess Who?. But, rather than admit defeat and break out the cards for a lonely game of solitaire this individual decided a better option would be to create a bio-molecular system to approximate a computational neural network that could be the guessing game partner. Well, I sincerely wish that scenario was the inspiration for the research that resulted in the recent Nature paper Neural network computation with DNA strand displacement cascades, but even if it wasn?t this is still one of the most creative and interesting takes on artificial intelligence I?ve seen.
Taking inspiration from the biomolecular circuits that guided the ?intelligent? behavior of individual cells, researchers at Caltech designed a system of four artificial neurons trained to recall four single stranded DNA sequences and can identify the most similar one when presented with incomplete patterns. Using a linear threshold function a single neuron was modeled. This function allows the ?neuron? to receive an imput that is then multiplied by a positive or negative weight and then based on meeting or exceeding a predetermined threshold the ?neuron? fires producing an output. The the DNA neurons made from 112 discrete strands were created and connected in a Hopfield associative memory. This network of 4 neurons makes a tiny biomolecular brain capable of some interesting tasks.
The CalTech researchers ?trained? the tiny brain to identify four scientists based on answers to four yes or no questions such as ?Is the scientist a mathematician?? The human player in this modified game of Guess Who? answers these questions with corresponding strands of DNA that go into the test tube with the artificial neurons. The network then communicates its guess via fluorescent signals or it indicates that not enough information was given or that there was a contradiction. The network came up with the correct answer in every trial.
This biomolecule based brain may prove to have many practical applications in several fields. Medically, it would be very beneficial to have cells capable of identifying and signaling the presence of certain molecules or processes involved in disease, and in chemical engineering complex compounds could be produced one molecule at a time using these networks. This is truly a novel approach to modeling the brain and one which may prove very useful in the future.

Presently, we live in a society that has become increasingly dependent of pharmaceuticals as the great panacea for our discomforts and diseases. Treatment of neurological disorders is most commonly mediated through trial and error dosing of medication. This trend has steadily increased since the 1950s with the use of antidepressants and accompanied the closing of most of America?s mental hospitals. The emphasis on personal treatment and therapy has lost ground to the administration of singular chemicals (or combinations) that alter pathways with predicted but not completely understood chemical results (due to the highly interconnected nature of these chemical pathways.) This method can work wonders, many patients with severely debilitating neurological disorders such as schizophrenia often find great relief in their treatments and are able to live without or with minimal assistance. Drugs are also often a cheaper solution to the problem (compared to high levels of therapy or institutionalization.)
Unfortunately though this practice of pharmaceutical treatment has many limits; Many antidepressants that have been prescribed over the years have been found later to increase suicidal tendencies. Some people have genetic or environmentally caused dispositions that increase or decrease the drug potency or its negative side effects. Some drugs are sought out not for curing disorders or diseases but for recreational or ability enhancing uses (like the highly prevalent the misuse of adderall among students.) Then, of course, there are disorders or injuries which impair the nervous system for which there is no known treatment or specific biochemical pathway on which to act upon. For these reasons many scientists and clinicians are using nonpharmacological treatments, especially the utilization of sensory input, to help ease and heal their patients.
A great leader in this movement towards alternative forms treatment is Dr. V. S. Ramachandran. Dr. Ramachandran is a neuroscientist at the University of California San Diego and has helped people suffering with a strange neurological disorder known as phantom limb syndrome without surgery or drugs. Phantom limb syndrome is the experience of feeling of the presence of an amputated limb, it can be quite painful and is believed to be caused by lack of feedback inhibition (the brain tells the missing hand to clench but the hand cannot clench so the brain tells the hand to clench harder etc.) By using a ?mirror box? Ramachadran has found that he can use external sensory input (the patient ?seeing? his missing hand clench by using the reflection of his present hand) to override the jammed signal.
Another example of novel drug-free therapies has been the use of electrodes to serve as external sensory devices in both the treatment of vestibular malfunction and to return sight to the blind. A grid of electrodes is used in both cases and can be used as a sort of balancing meter for vestibular treatment or as a sort of low resolution black and white television (with an on electrode being white and an off electrode being black.) These treatments have shown success for many patients and may become more popular as technology advances.
These exciting and alternative therapies are of course limited, but may open the door to other forms of treatment for difficult to medicate neurological disorders.

Have you ever experienced a ?gut feeling?? Gut feelings are also known as intuitions. I?m sure you?ve all hear about your mother?s intuition? if not ? I?m sure she?ll tell you ?Mother knows best!? We all know things that weren?t taught to us?but we still know them. For example, best friend says she?s ?okay? but you know she isn?t or your newborn is sick. A gut feeling is a sudden, unexplained judgment where we don?t know the source of origin.

Science has started to research how the stomach and brain are interconnected. ?The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language.?(Mayer, 2011)

In the August issue of Nature Review Neuroscience, the article ?Gut feelings: the emerging biology of gut?brain communication,? talks about the foundation of why there are such feelings and the pathways that are taken to create those feelings. ?Recent neurobiological insights into this gut?brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making.?(Mayer, 2011) The article discusses the enteric nervous system and the signaling pathways that the gut and brain used to communicate ??The brain communicates to the viscera, including the gastrointestinal tract, through multiple parallel pathways, including the two branches of the autonomic nervous system (ANS), the hypothalamic?pituitary?adrenal (HPA) axis and the sympatho?adrenal axis (modulating the gut-associated lymphoid tissue), and descending monoaminergic pathways (modulating gain of spinal reflexes and dorsal horn excitability). ? (Mayer, 2011) The article then discuss the effect of the stomach to the brain. Most of the consciously perceived information about the stomach is that it?s used for digestion?this isn?t new information. ?However, recent evidence suggests that various forms of subliminal interoceptive inputs from the gut, including those generated by intestinal microbes, may influence memory formation, emotional arousal and affective behaviours.? (Mayer, 2011)

So why do we make decision based off no information but off our ?gut feelings?? Mayer suggests that we have some ?neurological basis? when it comes to our gut-interactions. She suggests that our gut feeling based decision is due to an interoceptive map of gut responses that develops in infancy and continues to develop throughout our stages of life.

The future holds new research on the crosstalk between the stomach and the brain. The primary focus is the mapping associated with the two. ?This includes the remarkable success in mapping the functional neuroanatomy of the ENS, in our understanding of how the brain modulates these ENS circuits and gut functions, and in unraveling the complexity of gut to brain signaling through multiple parallel but interacting communication channels.? (Mayer, 2011) With our current advances in the study of gut feelings we still have many unanswered questions? stay tuned for what science discover next.
To read full article, please visit https://cuvpn.colorado.edu/nrn/journal/v12/n8/full/,DanaInfo=www.nature.com+nrn3071.html

Have you ever been frustrated while driving in traffic only to turn on the music and feel better? I believe that most people would agree with me when I say music is absolutely essential to life and can turn a bad day around with a simple chorus.

In January 2011 issue of Nature Neuroscience, the article "Anatomically distinct dopamine release during anticipation and experience of peak emotion to music", endogenous dopamine released in the striatum was found to occur at peak arousal while listening to music. Music often elicits feelings of euphoria and joy similar to the rewards involving the striatal dopaminergic system.

Of course everyone has their own taste in music and different songs give pleasure to different people. Thus, in this study the "chills" or "musical frisson" response, a commonly used marker of peak emotional response to music, was used. This technique involves a discrete pattern of ANS arousal which allows researchers to take a subjective phenomenon (pleasure to music) and pinpoint the precise timing of optimal pleasure. Participants were asked to choose their own pleasurable music and their psychophysiological responses, such as: heart rate and respiration rate, as well as brain imaging scans were taken while they listened. Two PET scanning sessions were conducted and the sessions showed an overall increase in ANS activity during the pleasurable music condition.

These researchers used fMRI's to image the route of dopamine release. They found that the caudate was more involved during anticipation and the nucleus accumbens was more involved during the emotional responses to music; indicating that enjoying your music can lead to the release of dopamine in the striatal system. More specifically the results of this study show that listening to music is associated with dopamine activity in the mesolimbic reward system. If "music-induced emotional states" can lead to dopamine release and subsequent feelings of happiness, it may explain why music is universally valued!

After reading this article I couldn't help but think about ELO's Mr. Blue Sky and how this song's lyrics allow me to feel joy regardless of where I am. With an upbeat melody and the lyrics:

Sun is shinin' in the sky
There ain't a cloud in sight
It's stopped rainin' everybody's in a play
And don't you know
It's a beautiful new day hey, hey

Runnin' down the avenue
See how the sun shines brightly in the city
On the streets where once was pity
Mister blue sky is living here today hey, hey

Mister blue sky please tell us why
You had to hide away for so long
Where did we go wrong?

Hey you with the pretty face
Welcome to the human race
A celebration, mister blue sky's up there waitin'
And today is the day we've waited for?

How could you not feel elated?!
To read this article or get more information, check out: https://cuvpn.colorado.edu/neuro/journal/v14/n2/full/,DanaInfo=www.nature.com+nn.2726.html.

Every now and again an idea or a thing comes along that strikes a nerve and resonates with everyone. In fashion in 2010 it was a pair of shoes by Alexander McQueen called Armadillos. Nobody didn?t have an opinion about these fantastical lobster claw monstrosities that were somehow beautiful despite their blatant disregard for the practical physics of human locomotion. Similarly in 2010 the field of optogenetics burst onto the scientific scene and absolutely enthralled the neuroscience community. While Lady Gaga popularized McQueen?s strange but fascinating shoes in her videos and the MET displayed a pair in a fashion exhibit, the equally intriguing discipline of optogenetics was named method of the year across all of science and engineering by the journal Nature Methods and laboratories across the globe scrambled to hop on the bandwagon. This month the journal Neuron published a primer titled Optogenetics in Neural Systems by researchers at Stanford University.
The primer gives a thorough context to this rapidly emerging field starting with none other than Francis Crick. In 1979 the famed scientist recognized that a major challenge facing neuroscience was the need for a cell specific stimulator that unlike the electrode would be able to control activity in one cell type while leaving the others unaltered. Later, he even went so far as to suggest light could be a useful tool, but did not make the connection between this thought and research done years earlier on the microbial single-component light-activated ion pump bacteriorhodopsin. It wasn?t until 2005 that introduction of an opsin gene into mammalian neurons resulted in the control of action potentials.
The discovery of the three classes of opsins (haloarchael bacteriorhodopsin ,halorhodopsin, and channelrhodopsin) is detailed along with their specific uses. These genes now allow neuroscientists to manipulate neurons and cause ?fast excitation, fast inhibition, bistable modulation, and intracellular biochemical signaling? on demand.
The paper further discusses targeting techniques such as viruses, projection targeting, transgenic animal targeting, and spaciotemporal targeting. Viral vectors such as lentivirus and adeno-associated virus have been successfully used to introduce opsins to mouse, rat, and primate brains, and projection targeting may prove even more exciting as it makes it possible to illuminate and excite cells based on their connectivity.
Not only does this primer provide a detailed background of optogenetics, but it touches on nearly every possible aspect involved in actually setting up a successful optogenetics rig in a laboratory setting including light requirements for activation, light delivery, and light sources (with sections on lasers, LEDs, and incandescent sources).
Unlike the Armadillo shoes, who despite the stir they caused in the fashion world last year have fallen off of the radar, optogenetics isn?t a passing fad. It is the beginning of a complete re-imagining of how we study the brain. It is by far one of the most creative and clever methods I have ever seen. It is ingenious in concept, but somehow simple and elegant when compared to complicated drug targets and indiscriminate electrodes. We are at a place in neuroscience where the advancements we are likely to see in even the next 10 years will be even more unbelievable than McQueen?s Armadillos becoming a staple in every woman?s wardrobe. I am excited to see the development in this field and I?m sure we will still be talking about optogenetics in 2012 even if next year?s foot fad has progressed to include ACTUAL armadillos. More here: http://www.cell.com/neuron/abstract/S0896-6273%2811%2900504-6

Many types of neurodegenerative diseases are the result of the malfunction of a particular brain system. For example the Parkinson?s disease is the result of a failure in the substantia nigra. This is believed to be caused by a down regulation of dopamine (and in fact Parkinson-like symptoms can be a side-effect to some anti-depressants that down regulate dopamine.)
In Neuron (July 14th 2011) an article entitled ?Selective Neuronal Vulnerability in Neurodegenerative Diseases: from Stressor Thresholds to Degeneration? reviews the progress of Huntington?s Disease, Parkinson?s Disease, Alzheimer?s Disease, and amyotropic lateral sclerosis and how even though they affect particular neural subpopulations within the brain giving rise to their unique symptoms. These individual diseases often have similar manifestations despite having different apparent ?causes.?

According to the article these diseases all share certain commonalities; They are often diagnosed by the accumulation of particular proteins (where and what unique to each disease.)These diseases are all considered proteopathies which means that proteins involved in the progression or development of the disease are abnormal. These diseases also often affect similar biological pathways. Finally all of these neurodegenerative disorders? likelihood of occurrence and symptoms increase as individual ages.

These neurodegenerative disorders can be familial (where an individual inherits genetic predispositions to the disease) or can appear sporadically but, interestingly enough, the diseases show very similar symptoms and affected neural systems. Some proteins may be more likely to be misfolded in general and this misfolding may increase in the presence of cell stress. These proteins accumulate in the endoplasmic reticulum and trigger another stress response termed the unfolded protein response. Malfunctions in proteins associated with this response have been shown to cause neural degeneration in animal models and is also thought to be associated with neurodegenerative disorder development.

Each neurodegenerative disease associated misfolded protein seems to preferentially accumulate in particular neural subpopulations. This makes the similarity of how the disease acts despite the different environmental or genetic causes make sense. These misfolded proteins may become involved in signaling cascades and further affect the vulnerable neuron?s homeostasis. Malfunctions in associated homeostatic pathways have been correlated with neurodegenerative diseases as well and have been shown to exist in conjunction with the previously mention endoplasmic reticulum stress response in diseased individuals.

Studies of misfolded protein amyloid deposits (found in Alzheimer?s patients) showed that the presence of deposits accompanied neural deficits similar to the early stages of Alzheimer?s but additional depression of the local environment was present in the cases of the full blown disease. This suggests that the accumulation of misfolded proteins is not enough to cause the disease but that there may be additional stressor required. These additional stressors can be the gradual degeneration due to aging, genetic mutations in related pathways, or a number of environmental stressors.

Some subpopulations of neurons initially vulnerable to accumulation of these misfolded proteins coupled with their accompanying stress-inducing response and other genetic or environmental stresses may in fact cause neurodegenerative disorders that originate in these affected systems. These vulnerable neurons may account for the similarity of disease despite its sporadic or familial origination.

How effective is your caffeine in the morning?
"Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine." How many cups do you drink in the morning before you feel like you are ready to take on the day? The average intake of caffeine is on average was 346 mg per day (equivalent to about three cups of ground coffee per day). What if I were to tell you that the coffee you are drinking scientifically isn?t helping that fatigue. "Although frequent consumers feel alerted by caffeine, especially by their morning tea, coffee, or other caffeine-containing drink, evidence suggests that this is actually merely the reversal of the fatiguing effects of acute caffeine withdrawal (James and Rogers, 2005; Sigmon et al, 2009)."

What if I were to tell you that caffeine has a negative side effect to your health, would you continue to drink it? Caffeine has been linked to hypertension, increased anxiety, nervousness, irritability and nausea. So why can coffee taste that good but have some many side effects? "These behavioral and physiological effects of caffeine occur primarily through antagonism by caffeine of the action of endogenous adenosine at adenosine A1 and A2A receptors (Fredholm et al, 1999)." This study has linked a SNP between caffeine and increased anxiety. "Specifically, it was found that 150 mg caffeine (equivalent to the amount of caffeine present in, eg, 1½ cups of ground coffee) increased anxiety in individuals carrying the TT genotype of the ADORA2A SNP rs5751876, but not in the CT and CC genotype groups (Alsene et al, 2003; Childs et al, 2008)." This study took 218 women and 198 men and administered two doses of caffeine 100mg in the morning and 150 mg shortly after. There was randomization on who would receive caffeine and who would have a placebo. The group of people took a pre-survey to make sure that all caffeine users drank approximately the same amount of caffeine. The day before the study, subjects were not allowed to drink anything that had caffeine in it. Surveys were given to check the anxiety, alertness and quality of headache.

"Another key finding of this study is that a clear anxiogenic effect of caffeine, larger i individuals with the ADORA2A rs5751876 TT genotype, was observed only for people who habitually consumed little or no caffeine (the N and L groups). Higher caffeine consumption appears to lead to substantial tolerance to this effect." They discovered that people who continue to drink caffeine at a high enough rate didn't experience the increased side-effects. They discovered that the subjects developed a tolerance to the caffeine. "Although frequent caffeine consumers experience minimal increased anxiety after caffeine consumption, they are at risk of at least two clear adverse effects of acute caffeine abstinence, namely low alertness and increased headache."

To sum it up people who are habitual users do not develop adverse side effects until they withdraw from the caffeine use. There is also research that has linked a SNP to increased anxiety secondary to caffeine assumption.
For reading of full article please visit http://www.nature.com/npp/journal/v35/n9/full/npp201071a.html

Think back to the high school adolescent movies that you have seen. Have you ever noticed that all the "cool" mysterious kids seem to smoke cigarettes? Most adult smokers start smoking before becoming 19 years old and 70% of young adults have admitted to trying a cigarette at least once in their life.

How about the fact that with the constant tobacco sales, we have seen an average increase of 5.5% in the rates of ADHD diagnosis every year since 2003? There is a connection! A recent study published in Nature Neuroscience shows that smoking cigarettes and exposure to nicotine during one?s adolescence may be the underlying cause of attention deficits. The study by Danielle S Counotte et al shows that nicotine exposure during these critical growing years causes a reduction in mGluR2 protein and function on the presynaptic terminals of PFC glutametergic synapses.

Counotte and her colleagues exposed adolescent rats to nicotine in order to observe the changes in attention keeping capabilities. Through the use of the 5-choice serial reaction time task, they found that nicotine exposure in adolescent rats increased impulsive behavior and impaired attention in adulthood after 5 weeks without nicotine exposure

In order to confirm that mGluR2 signalling in the PFC is involved in attention, MPPG (a mGluR2 antagonist) was infused into the mPFC of control rats. By decreasing the mGluR2 signaling in these animals, attention performance was reduced. mGluR2 receptors have been linked to the short term plasticity of glutamatergic synapses in cortical areas. Counotte further tested the role of mGluR2 in the short term plasticity of these synapses in adult mPFC and found that after 5 "clean" weeks, adolescents that were exposed to nicotine expressed less depression of mPFC glutamatergic synapses than in the rats treated with saline. A reduction in mGluR2 protein levels were also reduced in adolescents treated with nicotine. These results may explain the observed reduction in mPFC function and a lack of ability to pay attention.

This study also found that nicotine exposure during adulthood, however, did not affect mGluR2 protein levels after 5 weeks of abstaining from nicotine and did not reduce synaptic depression. Instead a slight increase of depression was observed; thus indicating that mGluR2 levels in the PFC are developed during and are particularly vulnerable to nicotine's effects during adolescence. Nicotine is able to pass through the blood brain barrier and binds to nicotinic acetylcholine receptors in the PFC. Huh. There is a reason why it's illegal to smoke cigarettes before turning 18!

As a nation, could we be causing our own increase in attention deficit disorders by making risky choices as young adults? This study leads me to wonder whether other ?common? ailments could be prevented if kids would just follow the rules.
For more information, this article can be found in the April 2011 issue of Nature Neuroscience and is entitled "Lasting Synaptic Changes Underlie Attention Deficits Cause by Nicotine Exposure During Adolescence".

We Americans are so accustomed to a lifestyle of instant gratification, ease, and leisure; especially when making daily choices of what we consume individually. It's no surprise we face an unprecedented epidemic of obesity in this nation when you look at how corporate food companies cater to our demand for easy availability of virtually any type of food one could ever crave. Obviously location takes an important roll as well, but for most of us residing in urban areas, our communities are saturated with endless food options. We no longer need to get out of our car to get an eight-hundred calorie caramel macchiato in the mornings. There's something to be said about the fact that one can obtain endless high-fat and high-caloric meals at the very thought of hunger.

Researchers and statisticians seem to be very compelled in not only updating the nation's obesity statistics, but also in finding new ways to potentially counteract America's modern obesity outbreak. In the past, some of us have resorted to other behaviors and procedures in compensation such as workout rituals, personal trainers, diet pills, and even extreme actions like stomach-stapling, liposuction, etc. Regardless of whether they worked or not, it's about time something new came around.

In last month's publication of Nature & Neuroscience, and interesting study using mouse mutants to research insulin receptor function in the ventromedial nucleus of the hypothalamus (VMH). Provided that high-fat diets lead to the production of severely high levels of insulin (which we all know can initiate cascades of detrimental health issues such as diabetes, high blood pressure, etc.), Klöckener et al. suggest brain mechanisms in the VHM which if genetically modified, may be applicable to humans and anti-obesity treatments.

The VMH is a rather unclear and grey portion of the brain in terms of the knowledge that we currently know about it. We do know however, that it serves as one of the primary locations in the hypothalamus that mediates nutrient sensing, metabolism, and insulin receptor signaling. To guarantee an optimal energy environment for reproduction, the body monitors energy availability indirectly with the help of insulin and leptin that consistently circulate in the body. These two hormones can act to store fat as well as alert other metabolizing processes.

Steroidogenic factor 1 (SF-1) positive cells distribute across large parts of the VMH are directly involved with controlling systematic metabolism. These cells are highly responsive to insulin. Klöckener et al. identified a subpopulation of insulin-SF-1-positive cells in the VMH distinct from leptin-responsive neurons. They found that the systematic deletion of the insulin receptor in SF-1 expressing cells of the VMH caused no immediate changes in homeostasis. However, when both the control and mutant mice were exposed to high-fat diets, the modified SF-1 cell mice were protected from the development of obesity. It was reasoned that this protection from obesity was due to higher leptin sensitivity, since insulin was rendered useless in the mutant mice. Following this discovery, they found that the reinstatement of PtdInsP3 signaling downstream of the insulin receptor made the mutant mice that were previously protected from obesity, vulnerable again.

Even though all of the processes VMH carries out sill remains unclear, the mechanisms involved with insulin and high-fat diets are becoming clearer. These findings are on their way to future investigations where potential anti-obesity therapeutics may be revealed.

I think it's awesome that researchers are unveiling new methods that can potentially solve this epidemic in the near future and I strongly support such research for the benefit of the population. This compelling issue has not been mitigated to a satisfactory level even with counteracting behaviors as mentioned above. Statistically, just below twenty percent of the population in Colorado is diagnosed as clinically obese. It's ironic thought because Colorado tops the list for the least obese state in the nation. We clearly have to keep working, researching, and making changes in order for a valid solution to be found.

The response of a brain while listening to music is very different than the response of the brain to many other types of stimuli. While observing a scene there is no direct way to see how the brain is processing the image. Many different part of the brain must integrate the cloudy points of stimulation (or lack of stimulations,) pattern recognition, and memory among other things for the person to perceive what it is they are looking at. It is a very subjective experience that is difficult for a neuroscientist to analyze. Sound on the other hand (especially simple rhythmic sound) is often very directly observable by many available neurological measurements including EEGs. This has recently been the center of much attention in neuroscience and had provided fodder for several books including This is Your Brain on Music by Daniel J. Levitin and Musicophelia by Oliver Sacks.
EEG studies of patient response to rhythmic beats is the focus of Tagging the Neuronal Entrainment to Beat and Meter from the Journal of Neuroscience published this July. This study tries to delineate how the human mind processes beats and meter in general. Previously many studies were done exploring how musical meter can create an expectation in the listener, you have probably experienced this yourself by tapping your foot to a song you?ve never heard before. Most music (maybe excluding some jazz and freeform types of music) follows some predictable pattern and our brains zero in on them (wonderful recognizers of pattern that they are.)The theory of resonance has been proposed to explain these observances hypothesizing that after certain exposure to the rhythmic beats (or music) large groups of neurons become ?entrained? and resonate at frequency correlating with the music?s beat. By altering the beats from what is expected scientists have studied what the call evoked potentials (or EPs.)
In the studies done in this particular article researchers at the Institute of Neuroscience of the Universite Catholique de Louvain in Brussels, Belgium had participants listen to a 2.4 Hz beat an imagine it as either a binary beat (1 2, 1 2, 1 2, as in a march) or ternary (1 2 3, 1 2 3, 1 2 3, like in a waltz.) As a control they had some participants listen to the beat but did not instruct them to image a particular meter. They then monitored the response of the participants? EEGs. The researchers found that EEGs showed increases in amplitude of subharmonic frequencies in the groups that were imagining the binary and ternary beats. That means in the control group they showed a strong 2.4 Hz signal the binary group showed strong 2.4 and 1.2 Hz signal and the ternary group showed strong 2.4, 1.6, and .8 Hz signals. This supports many of the previous research done on this topic showing that direct observation of the physical experience of music can be measured and quantified using existing mode of neurological research. This may open doors to understanding how the brain processes other types of stimuli and art in the future.

I have a very good friend who has a terrible infatuation with glia. Unfortunately in the circles he runs in there are few people with whom he may share his strange fascination without facing merciless ridicule. It seems that in neuroscience you are either in the camp that secretly adores the astrocytes or the one that likes to compare the poor glial cells to the kids who ate their paste in kindergarten. Glia are referred to as housekeeping cells and I?ve heard them called the ?brain?s janitorial staff?, so I sympathized with the lowly glia- dutifully picking up after the all important neurons who were concerned with much more important things- but little did I know these humble glial cells are actually running the show from the start.
In a recent article in Nature Neuroscience researchers found that glia secrete a TGF-b ligand called myoglianin (myo) that actually informs developmental remodeling of neurons. It is well known that as an organism matures its neural circuits are altered and refined, but this study sheds light on the process that triggers this developmental frenzy of cerebral landscaping. In insects such as Drosphila, larval neural circuits are transformed during metamorphosis into adult ones. Neurites are pruned and then extended to form ?adult-specific neural circuits?. This process is highly dependent on TGF-b signaling as it upregulates the expression of EcR-B1 in the late larval stage. Also at this stage myo is secreted in a flood by larval glial cells. When the expression of myoglianin was silenced, the pruning and re-extension of larval neurites did not occur. The very form a brain takes is influenced from the beginning by glia. Without glia and myo these drosophila retain their larval neural network because superfluous connections aren't pruned and important "adult" networks aren't reinforced and strengthened.
It?s easy to make fun of glia, but they aren?t useless or dumb. They may be housekeepers, but they are the housekeepers from Gosford Park. Glia only let neurons THINK they are in charge. The truth is that glia deserve the same respect as neurons, and this is blatantly obvious when you look at diseases of the brain that origninate in or affect glial cells such as Parkinson?s and Alzheimer?s diseases. The roles that glia play are vital to the health of our brains and when they cease to function normally so do we. I think this study may be important in illuminating how glia may influence synaptic plasticity and long term potentiation in neural circuits. This is an exciting time for fans of glia.
Full article can be found here.
http;//www.nature.com+nn.2833.html

Depression... Baby or no Baby?
"Postpartum depression (PPD) affects up to 19% of all mothers and adversely influences maternal adaptation to motherhood (Gavin et al, 2005) with negative effects on child development, as children of depressive mothers are more vulnerable to develop mental disorders in later life." (Grace et al, 2003)

Every father remembers the day they found out that their wife was going to have a baby! With all the excitement, most fail to acknowledge the mood swings between trimesters and well after the pregnancy. There is more to pregnancy then peanut butter and pickle sandwiches. So, what gives? As the growing baby starts to develop so do new hormones and hormone levels also increase.

Oxytocin is one of the first identified polypeptide hormone also known as the "love hormone." Oxytocin is responsible for increase bonding feeling associated with pregnancy. This study suggests that low levels of oxytocin have a higher risk of postpartum depression. There are other risk factors that can increase chances of postpartum depression such as age under 20, drug/alcohol abuse, increase emotional vulnerability and lack of support.

This study proposed by National Centre of Competence in Research (NCCR) Swiss Etiological Study of Adjustment and Mental Health took 75 pregnant females and tested their levels of oxytocin during the last two weeks of their third trimester along with two weeks after giving birth. After their study they concluded that increasing the level of oxytocin during pregnancy could decrease the severity of postpartum depression.

The researchers did their best to find equal candidates for the study. The research was focused on same age females within the same economic status along with a healthy pregnancy. "A detailed study description was given to all interested women and, if any raised, questions were answered. All participants were screened for the following inclusion criteria: (a) no current mental illness, (b) no severe medical complications (acute or chronic physical diseases, such as gestational diabetes, metabolic diseases, hypertension and thyroid dysfunction), (c) no signs of fetal malformation, (d) a pre-pregnancy BMI below 32, (e) no smoking beyond the 10th week of gestation and (f) good knowledge of German language."

The researchers also discuss that this is one of the first studies done to link postpartum depression and oxytocin levels. They stated that more research needs to be done to see if increasing the levels of oxytocin could help prevent postpartum depression in females. One thing that they acknowledge is that the environment could be influencing the sign and symptoms of postpartum depression.

This was very informational article about oxytocin and postpartum depression. One thing that I find myself amazed on is that oxytocin is also given to induce labor. If increasing the levels helps prevent postpartum depression at what point do we higher the levels, hours before pregnancy, days before or weeks before? If we raise the level, will this also induce labor at a unsafe time in pregnancy?

If you are interested in the original article please reference this online journal at http://www.nature.com/npp/journal/v36/n9/full/npp201174a.html

As people we all vary in personality, thought and emotion. We all know that. But, when it comes to the world we live in, does everyone see the same things? If I look at a beautifully orange colored flower, does the person sitting next to me see what I see? According to a study by Dr. Samuel Schwarzkopf the answer to this question may be no.

In Dr. Schwarzkopf's recent study, a negative correlation was found between the size of an individual?s central visual field, as defined as the surface area of a person's primary visual cortex (V1), and the magnitude of illusory perceptual effect of two different optical illusions. The first optical illusion is the Ebbinghaus illusion where two central circles are identical in size but appear to be different sizes to the viewer because of the surrounding circles. One circle is surrounded by 6 larger circles and the other surrounded by 8 smaller circles. The second illusion come from Ponzo and is an illusion in which two checkerboard circles are identical in design and size but appear different because of the three dimensional background.

The two illusions may have different mechanisms behind their perception. The article predicts that the Ebbinghaus illusion may be associated with the lateral connections in V1 and the Ponzo illusion mediated by "feedback projections from the areas that extract the three dimensional context of the background".

The subjective experience of how large the circles looked varied between subjects. As I previously stated, in a large sample population, Schwarzkopf found a significant negative correlation between the magnitude of both illusions and the surface area of V1. Using standard retinotopic mapping procedures with functional magnetic resonance imaging (fMRI), participants with a small functionally defined V1 surface area were found to have stronger perceptual illusion than subjects with a large V1. There was no significant correlation found between the V2 or V3 visual regions and magnitude of the size illusions.

The study mentions that future work will look into whether the individual differences found can be attributed only to V1 surface area size or whether other mechanisms such as the concentration of the inhibitory neurotransmitter GABA or possible differences in actual brain structure. Furthermore, individual differences in size perception exist but are there commonalities among similar populations? For example: do people with autism see sizes more similarly than when an autistic person is compared to a person with brain activity attributed with normality? What about the effect of color blindness on size perception?

Schwarzkopf's study helps remind us of the variations in brain structure that contribute to each of us being who we are. If we all see things differently, how does the way we see something affect how we feel about it?

The article detailing Schwarzkopf?s study can be found in Nature Neuroscience at http://www.nature.com/neuro/journal/v14/n1/full/nn.2706.html

In Mike Nichols film "The Birdcage," Albert played by Nathan Lane, is an insecure, emotional-rollercoaster drag queen whose partner Armand, played by Robin Williams, is an unwavering, cautious entrepreneur. Albert's insecurities get the best of him on stage in addition to his relationship woes that cause him to act in a neurotically unstable fashion. When his self-image gets the best of him, he relies on "Pirin" tablets supplied by his houseboy to calm his nerves and give him so called confidence so he can perform on the stage, and keep the guests coming. Completely clueless to the fact that the "Pirin" tablets are just aspirin tablets with the "A" and "S" scratched off, Albert's "need" for them remains a religious habit.

Albert's surrender to the placebo effect isn't necessarily out of the norm when taking the general population into perspective. Research published in the Journal of Neuroscience surrounding the neurobiological mechanisms of the placebo effect could be used as an excuse as to why people like Albert succumb to pseudo-western medicine prescriptions and expectations to better their condition.

The placebo effect is a psychobiological phenomenon that can be attributable to different mechanisms, including expectation of clinical improvement. In Fabrizio Benedetti's research encompassing this effect, he notes that no matter what medical treatment a patient is receiving, their therapeutic outcome is surrounded by psychosocial contexts. The placebo effect has become a modern topic of interest among scientists and the general public in light of the fact that "we must broaden our conception of the limits of endogenous human capability."

If we can rely on our own homeostatic processes and reduce our usage of unnecessary western medications, some of which have detrimental side effects later in life, we can potentially better our overall well being. In Parkinson's disease research, a pool of patients was given an inert substance (the placebo) and were told that it was an "antiparkinsonian drug that produces an improvement in their motor performance." Results displayed that with their capability to measure endogenous dopamine release, the placebo-induced expectation of motor improvement activates endogenous dopamine in those patients. This ultimately led the patients to better therapeutic outcomes.

We know that the placebo effect is real. Patients involved in thousands of placebo-induced studies have shown a better therapeutic outcome when their expectations and knowledge of recovery is good. Recent uproars are now suggesting the idea of anti-depressant medications being glorified placebos. On account of the pharmaceutical boom for mental illnesses, scientists are heavily researching not only the accuracy of such drugs but the validity.

What does this mean for the Albert's of the world and the rest of us taking conceptually risky medications? Well, even though the thought of people halting their prescription use and relying on their endogenous human capability to run the ship seems amiable, it's not practical. People need medications. However, I definitely think pharmaceutical companies are where the problem lies. How do we know that the neurological drugs that our doctors are telling us we need are in fact necessary or even beneficial for that matter? We don?t. But there's no reason why we shouldn't question the men and women who attended a higher level of education to write us these prescriptions.

Those of us in dating in high school in the late 80′s can attest to the stinging truth revealed in Def Leppard?s song, ?Love Bites? shortly after a nasty break-up. But it was only recently that scientists employing state-of-the-art brain imaging fMRI technology have been able to view the similarities between the biting pain of rejection from a lover and physical pain.

A study published in the April 12 issue of Proceedings of the National Academy of Science (PNAS) has provided the most direct evidence showing a common brain circuit underlying the pain of rejection and physical pain.

In their study, the researchers at Columbia University, University of Michigan and University of Colorado, Boulder studied 40 subjects who had experienced rejection and break-up with a lover within the past six months. They tested each subject on two tasks, a social rejection task and a physical pain task, while imaging their brains.

In the scanner, subjects looked at the faces of their ex and thought about how it felt during their split and a snapshot of their brain was taken. Next they were shown a headshot of a friend of the same sex as their former partner and thought about a recent positive experience they shared. This provided the social rejection condition.

To compare the social rejection experience to the experience of ?physical pain? they attached a thermal device to the volunteers? forearms and set it to produced a ?painful?, but not harmful level.

In both men and women, rejection and painful heat activated brain circuits underlying distress (e.g. Anterior Cingulate cortex) and the sensation of pain e.g. somatosensory cortex).

Although this seems seems intuitive from centuries of poetry, tragic plays and lyrics, knowledge at a mechanistic level showing the same circuits are activated gives scientists new ways to deal with both. It makes one wonder if taking pain-killers shortly after a break-up might be a treatment option.

The common mechanism between social rejection and physical pain may be one reason why heroin and alcohol, both analgesics for pain, are irresistible amongst country and grunge musicians whose melodic ruminations center on tragedy, angst and painful relationships. Kurt Cobain comes to mind when he said, ?Thank you for the tragedy. I need it for my art.?

Last year the British pop group ironically named, ?The Wanted?, brilliantly connected the idea that pain from being unwanted/rejected and searing physical pain were one and the same in their popular song ?Lose My Mind?. Here are the lyrics and the video

They say that time
Heals everything
But they don?t know you
And the scars you bring

?Cos you left a jagged hole
And I can?t stand it anymore

If heartache was a physical pain
I could face it I could face it
But you?re hurting me
From inside of my head
I can?t take it I can?t take it

I?m gonna lose my mind
I?m gonna lose my mind

I?d erase my thoughts
If only I knew how
Fill my head with white noise
If it would drown you out
Kill the sound

If heartache was a physical pain
I could face it I could face it

But you?re hurting me
From inside of my head
I can?t take it I can?t take it

I?m gonna lose my mind
I?m gonna lose my mind

And I?d rather be crazy
I?d rather go insane
Than having you stalk
My every thought
Then having you here inside my heart

If heartache was a physical pain
I could face it I could face it
But you?re hurting me
From inside of my head
I can?t take it I can?t take it

I?m gonna lose my mind
I?m gonna lose my mind