Fuck yeah, Endocrinology!

“This is Jeremiah. Jeremiah wore safety goggles while angle grinding. Jeremiah still has his right eye. Be like Jeremiah.”

Bravery Cells Found in the Hippocampus 

(Image caption: Super-resolution microscopy reveals active release sites (green) on dopamine neurons (purple) for the first time. Animation: Pascal lab)

Zeroing In on Dopamine

Among the brain’s many chemical messengers, few stand out as much as the neurotransmitter dopamine. Linked to love, pleasure, motivation and more, dopamine signaling plays a central role in the brain’s reward system. It is also critical for processes such as motor control, learning and memory.

Malfunctioning dopamine neurons have been implicated in numerous disorders, including Parkinson’s, schizophrenia and addiction. Because of its importance in the brain, researchers have studied the neurotransmitter for decades, making great progress in understanding its activity and when it goes awry.

Less is known, however, about the mechanisms that healthy dopamine cells use to release the neurotransmitter, a gap that has limited scientists’ ability to develop treatments for a range of dopamine-related conditions.

Now, researchers from Harvard Medical School have for the first time identified the molecular machinery responsible for the secretion of dopamine in the brain.

Their work, published online in Cell on Feb. 1, identifies specialized sites in dopamine-producing neurons that release dopamine in a fast, spatially precise manner—a finding that runs counter to current models of how the neurotransmitter transmits signals in the brain.

“The dopamine system plays an essential role in many diseases, but fewer studies have asked the fundamental question of how healthy dopamine neurons release the neurotransmitter,” said senior study author Pascal Kaeser, assistant professor of neurobiology at HMS.

“If your car breaks down and you want it fixed, you want your mechanic to know how a car works,” he added. “Similarly, a better understanding of dopamine in the laboratory could have a tremendous impact on the ability to treat disorders in which dopamine signaling goes awry in the long term.”

Dopamine research has largely centered on its dysfunction and on the protein receptors that neurons use to receive dopamine, said Kaeser. Despite the neurotransmitter’s importance, studies on how it is released in the brain under normal circumstances have been limited, he added.

Promiscuous No More

To identify the molecular machinery responsible for dopamine secretion, Kaeser and his colleagues focused on dopamine-producing neurons in the midbrain, which are involved in the neural circuitry underlying movement and reward seeking.

They first searched for active zones—specialized neurotransmitter release sites located at synapses, the junctions that connect one neuron to the another. Using super-resolution microscopy to image sections of the brain into which dopamine neurons project, the team found that dopamine neurons contained proteins that mark the presence of active zones.

These zones indicate that a neuron may engage in fast synaptic transmission, in which a neurotransmitter signal is precisely transferred from one neuron to another within milliseconds.

This was the first evidence of fast active zones in dopamine neurons, which were previously thought to engage in only so-called volume transmission—a process in which the neurotransmitter signals slowly and nonspecifically across relatively large areas of the brain.

Active zones were found at lower densities in dopamine neurons than in other neurons, and additional experiments revealed in detail how the neurotransmitter is rapidly secreted and reabsorbed at these sites.

“I think that our findings will change how we think about dopamine,” Kaeser said. “Our data suggest that dopamine is released in very specific locations, with incredible spatial precision and speed, whereas before it was thought that dopamine was slowly and promiscuously secreted.”

In another set of experiments, the researchers used genetic tools to delete several active zone proteins. Deleting one specific protein, RIM, was sufficient to almost entirely abolish dopamine secretion in mice. RIM has been implicated in a range of diseases including neuropsychiatric and developmental disorders.

Deleting another active zone protein, however, had little or no effect on dopamine release, suggesting that dopamine secretion relies on unique specialized machinery, the authors said.

“Our study indicates that dopamine signaling is much more organized than previously thought,” said study first author Changliang Liu, an Alice and Joseph Brooks Postdoctoral Fellow and a Gordon Fellow in the Kaeser lab.

“We showed that active zones and RIM, which is associated with diseases such as schizophrenia and autism spectrum disorders in human genetic studies, are key for dopamine signaling,” Liu said. “These newly identified mechanisms may be related to these disorders and may lead to new therapeutic strategies in the future.”

The team is now working to investigate these active zones in greater detail to build a deeper understanding of their role in dopamine signaling and how to manipulate them.

“We are deeply invested in learning the entire dopamine signaling machine. Right now, most treatments supply the brain with dopamine in excess, which comes with many side effects because it activates processes that shouldn’t be active,” Kaeser said.

#Repost @mediczarmy Clubbing is changes in the area under or around the toenails and fingernails that occur with some diseases. The nails also show these changes.

Stars in (between) your thighs!

Stellate holes in some reproductive organs*!

What are they?

i♡histo

*Technically one is urinary not reproductive, but for the sake of the title of this post it’s close enough!

Answers soon!

Does Zapping Your Brain Increase Performance?

Here is a picture of the nine-dot problem. The task seems simple enough: connect all nine dots with four straight lines, but, do so without lifting the pen from the paper or retracing any line. If you don’t already know the solution, give it a try – although your chances of figuring it out within a few minutes hover around 0 percent. In fact, even if I were to give you a hint like “think outside of the box,” you are unlikely to crack this deceptively (and annoyingly!) simple puzzle.

The Nine Dot problem: connect the dots by making four lines, without lifting your pencil from the paper

And yet, if we were to pass a weak electric current through your brain (specifically your anterior temporal lobe, which sits somewhere between the top of your ear and temple), your chances of solving it may increase substantially. That, at least, was the finding from a study where 40 percent of people who couldn’t initially solve this problem managed to crack it after 10 minutes of transcranial direct current stimulation (tDCS) – a technique for delivering a painlessly weak electric current to the brain through electrodes on the scalp.

How to explain this?

It is an instance of the alleged power of tDCS and similar neurostimulation techniques. These are increasingly touted as methods that can “overclock” the brain in order to boost cognition, improve our moods, make us stronger, and even alter our moral dispositions. The claims are not completely unfounded: there is evidence that some people become slightly better at holding and manipulating information in their minds after a bout of tDCS. It also appears to reduce some people’s likelihood of formulating false memories, and seems to have a lasting improvement on some people’s ability to work with numbers. It can even appear to boost creativity, enhancing the ability of some to make abstract connections between words to come up with creative analogies. But it goes further, with some evidence that it can help people control their urges as well improve their mood. And beyond these psychological effects, tDCS of the part of the brain responsible for movement seems to improve muscular endurance and reduce fatigue.

It’s an impressive arsenal of findings, and it raises the obvious question: should we all start zapping away at our brains? That certainly seems to be the conclusion reached by the growing DIY community experimenting with home-made tDCS headsets.

But, while the list of supportive studies is far longer than those linked to here, the overall state of the evidence nevertheless continues to occupy that frustrating scientific limbo of being ultimately ambiguous – especially when we take into account all those comparatively boring, non-headline grabbing studies that found no significant effect from tDCS. In fact, a meta-analysis of tDCS studies – one of those laborious studies that study the findings of other studies – found the technique had no effect at all on a wide range of cognitive abilities. Yet that review in turn has been criticized as being too conservative and potentially biased in its own analysis.

More to the point, few of these studies have yet to be replicated, and most of them rely on a handful of unrepresentative people (US undergrads) who are asked to undertake the kind of lab-controlled tasks that usually share a questionable (at best) relationship with real world activities. And as for the long-term effects of tDCS use, or even how it affects brain function exactly? It’s not clear.

Yet none of this haziness has deterred start-ups from developing a slew of commercial tDCS headsets targeting home-users. Primary among those is Foc.us, which started off with a headset that allegedly enhances gaming ability before expanding to ones that improve learning speed as well as athletic endurance. There’s also Thync, a mood-enhancing headset that’s been described as a “digital drug” that can help users “energize or relax without drinks or pills.” While not quite based on tDCS, it uses pulses of electricity to target cranial nerves just under the skin to supposedly induce various moods.

Another such start-up, Halo Neuroscience, recently introduced its own headset, which stimulates motor neurons in a way that supposedly accelerates the strength gains and skill acquisition of athletes.

The firm reports on its own unpublished “preliminary results” with elite Olympic ski jumpers showing a 31 percent improvement in their propulsion force, with significantly less wobble when airborne. Even if a far more modest result than 31 percent turned out to be true, these sorts of findings could mean that tDCS is set to become a significant performance enhancer in the sporting world. Will its use in competitive settings be considered cheating?

In academic contexts, some universities are already trying to curb the off-label use of prescription drugs to enhance academic performance, with Duke University explicitly considering such use as “cheating.” Similarly, the Electronic Sports League, which holds massive gaming tournaments with million dollar prize pools, has started randomly testing players for so-called “smart drugs” that may give e-athletes an edge over their non-doping opponents.

Would using Foc.us’s GoFlow to “learn faster” be considered a similar instance of academic dishonesty by Duke University? Or what about using Foc.us’s gaming headset in the context of shooting down virtual enemies? If these devices give any sort of a boost, it’s not clear why their use should be considered any different from drugs like Adderall or Ritalin, at least in regards to cheating.

In non-virtual sport, the World Anti-doping Agency (WADA) prohibits substances and methods when they satisfy any two of these three criteria: 1. they confer a performance enhancement; 2. they pose an actual or potential risk for athletes; and 3. they violate the “spirit of sport.”

If the preliminary findings from Halo Neuroscience on ski jumping are even remotely valid, the first criterion would certainly be met. On the other hand, it’s not yet clear if tDCS poses a noteworthy potential risk for athletes – though any such risk would almost certainly be smaller than the one involved in soaring over 100 meters through the air, as in the case of ski jumping. But does it violate the difficult to define “spirit of sport”? It’s a question that WADA may wish to avoid: to answer yes may commit it to trying to ban the unbannable. As far as we can tell, tDCS leaves no uniquely detectable impact in the brain: a ban would not be enforceable.

On the other hand, tDCS may simply be construed as not “artificial” enough to threaten our (often arbitrary) notions of fairness, whether in sports or academic settings. Unlike injecting or ingesting a synthetic drug, many may have the intuition that a weak electric current is comparatively “natural” or “clean.” For instance, even though the effects are similar, WADA currently tolerates athletes who increase their red blood cells (and therefore, presumably, their performance) by sleeping in a tent that simulates high altitude, but not those who do so by blood doping or EPO. Something about sleeping in a tent to enhance performance does not strike us as suspect in the way that drugs or blood transfusions do. Perhaps tDCS will be occupy the same corner as altitude tents: for the rule makers, both can be convenient inconsistencies in the rules, as both elude detection anyway.

An yet, while we can question the evidence for the actual efficacy of most performance enhancers currently used, tDCS in particular stands out in calling for more data. Unlike Adderall or anabolic steroids, at the moment anyone can get their hands on a tDCS headset by legally ordering one online. And even if these headsets become more closely regulated, people can still cheaply make their own using common items found at electronics stores, stimulating any part of their brain, or their children’s. Given the current hype around it, it would be good to know more about how exactly it impacts the brain — and the long term consequences.

Top Image: These are increasingly touted as methods that can “overclock” the brain in order to boost cognition, improve our moods, make us stronger, and even alter our moral dispositions. Credit: Fabrice Coffini/GettyImages

Elderly male with reduced lung function. What is the diagnosis?

ANSWER: http://goo.gl/BqoBPG

Oxytocin

One of two hormones secreted from the posterior pituitary gland

Primarily responsible for facilitating birth and maternal bonding

Often referred to as the “love” hormone for its possible role in pair bonding, social recognition, trust, and empathy.

One of the few hormones that works on a positive feedback loop as opposed to the more common negative feedback loop.

A synthetic form is used to induce labor and because synthetic Oxytocin gets destroyed in the GI tract, it must be administered intravenously or in a nasal spray.