The Unsung Scientist, Louis-Antoine Ranvier

To many who read this blog, Notes of Ranvier is a title that probably evokes no thoughts of science or history. There is a backstory to the name, however, and a reason why I chose it as the title.

Notes of Ranvier is meant to be a play on words referring to the nodes of Ranvier, anatomical structures in certain types of neurons that have a myelin sheath. Every neuron has a long projection called an axon that transmits electrical signals to other neurons. Around the axons of some neurons is the myelin sheath, a fatty tissue that insulates the axon like plastic around a copper wire. Electricity can't travel though myelin, so there are even gaps between the sheath where the neuron is exposed and electrical currents can be propagated down the axon. These gaps were discovered by French scientist, Louis-Antoine Ranvier (pronounced rahn-vee-yeh), and thus bear his name as Ranvier's nodes or the nodes of Ranvier.

When you learn about Ranvier's nodes in class, not a lot of attention is paid to how they were discovered or why they have Ranvier's name instead of some other scientist. The treatment of the subject is far more along the lines of, "these exist, this is what they do, moving on." But the question still gnaws, who was Ranvier? How did he find these nodes, and how did he figure out what they do?

Ranvier was a histologist in 19th century France. Histology is the study of organic tissues, employing techniques such as staining and preserving tissues and examining them under a microscope to better understand their anatomy and physiology. When you looked at slides of cells dividing in high school biology, you were performing histology.

While histology and microscopy are so common today that even small children learn how to use microscopes in class, the microscope was renounced by many French scientists and doctors in the 19th century. The dismissal of the microscope was largely related to the dismissal of the cell. Even as late as the 1800's, the theory of the cell being the building block for all living things was still pretty far-fetched to many scholars. This idea known as cell theory, was hotly debated for centuries. But in the latter half of the tumult was Ranvier holed away in his laboratory, with his icepick of a microscope, diligently scratching and scraping on the surface of physiology.

From the time Ranvier was born in 1835 to the peak of his career, histology began to make a sea change in the eyes of French scholars. Histologists were developing newer and more advanced techniques for preserving and staining samples. Ranvier saw the merits of histology for studying anatomy and physiology. In particular, he valued the scrupulousness involved in preparing tissues for histological examination which allowed him to reveal the nodes between myelin sheaths and determine their function.


For a long time it was known that myelin sheaths existed and that they were made up of fatty cells. The cells were and still are called Schwann, after the scientist who identified them. Ranvier wanted to better understand how cells insulated by myelin sheaths were able to exchange nutrients (such as oxygen and ions) with the blood since carmine tissue stains demonstrated that such nutrients could not penetrate through Schwann cells. Closer examination with different chemicals and a more exacting technique revealed the nodes pictured below.

Ranvier's Nodes (e). Image from Barbara, J (2007). Originally from Ranvier, 1878.

Ranvier wasn't finished there. He still wanted to know whether the nodes really were the site for nutrient exchange between the neuron and the capillary. Around the neurons in your body is a small sheet of connective tissue that protects them from mechanical damage. Ranvier destroyed this tissue, and then poured water onto the exposed nerves of living animals. This caused the Schwann cells to swell and expand to cover the nodes. The result? A loss of neuron function and paralysis. Ranvier correctly deduced that the nodes were important for the conduction of signals through neurons.

Ranvier went on to develop some of the first legitimate theories on nerve cell degeneration with his experiments on myelin. Meanwhile, furious debate raged on about the nature of cells and their contributions to the function of the human body. Ranvier, all the while, was only interested in facts and improving his histological techniques. His mentality led to many great discoveries in his life, some of which contributed to our modern understanding of neurophysiology.

He was a man truly deserving of respect and admiration, and his approach to his work should be an inspiration to scientists and science writers alike.

Sources:
Bracegirdle, B. The History of Histology: A Review of Sources. (1977) Hist. Sci., 15:77-101

Barbara, J. Louis Ranvier (1835-1922): The Contribution of Microscopy to Physiology and the Renewal of French General Anatomy. (2007). Journal of the History of Neurosciences, 16:413-431.

Ranvier Returns

Hey everyone! I just wanted to write this to explain my absence.

In the last few weeks I left my job at the lab and decided to move back home to Ohio. I did this because I wanted more time to focus on what I really want to do, which is to write about science. The first step in that process, after the move, was to attend the science writer's workshop in Santa Fe, NM. I learned a lot there and came home feeling renewed and inspired. If you are reading this and are interested in getting into science writing yourself, I highly recommend you click that link above and apply to go to the workshop next year.

Over the next year I would like to write a lot more, but hopefully write for publications as well as here on this blog. So I'll be coming back with actual stories and new posts soon! I'm hoping to revise some of my older posts to make them better, too. If you want to stay up to date with me, follow me on twitter @NotesOfRanvier. I'll also be making a page on Facebook soon, too. So be on the look out!

Here are some photos from Santa Fe:

At the School for Advanced Research 

Prickly Pear Margaritas -- Yum!

I'm not really sure who this lady is or what she was doing but she looked cool so I took a picture.

More Notes of Ranvier soon.

Salty Penguins Filter Salt Out Their Nose

The Venture Brothers season 1, episode 5, via [adult swim]

Why yes, penguins do have an organ that converts sea water into fresh water! Except it's not an organ, it's a gland. And it doesn't directly convert sea water to fresh water, it filters salt from the blood.

Hm, maybe I should start from the beginning.

First of all, this organ/gland/whatever that Dean is talking about is called the supraorbital gland, and it's something all marine birds have. Basically any mammal or bird that is going to have to drink sea water to quench thirst is going to need this gland.

Normally, salt that we ingest is absorbed into the blood stream, filtered out by the kidneys, and secreted in urine. However, the penguin's small kidneys can only filter out enough salt to create urine that's about 1/3 the concentration of sea water. If the blood is still too salty, then water must be taken from other tissues to dilute it, and this quickly leads to dehydration.

Penguins have a very high salt load because they drink sea water to quench thirst and eat a lot of salty foods like crustaceans. Located above the nose, in between the eyes, the supraorbital gland lends a helping hand. Both the kidney and supraorbital gland filter salt from the blood in a process called counter-current exchange.

The blood flowing along the gland and the fluid within the gland flow counter, or in opposite directions to one another. One of the principles of osmosis is that molecules will move from fluids with high concentrations of solutes (in this case, salt) to fluids with lower concentrations. I.e. they move down their concentration gradient. So salt leaves blood and goes to the relatively less salty fluid in the duct. Since the blood and the duct fluid are moving in opposite directions, the blood will always remain saltier than the duct fluid, therefore a concentration gradient will be maintained, and the salt will always flow out the blood to the fluid in the duct.

Still confused? There's a pretty great diagram here. For the more verbally inclined, here's a metaphor: Imagine the blood stream and the fluid stream are two trains moving parallel to each other in opposite directions (I promise this won't involve any math). Every car in the "blood" train is full of (rather salty) people, and every car in the fluid train is empty. As the trains meet, the first two cars of each train will be facing each other, and the people from the blood train (with great nimbleness) will jump from the blood train to the fluid train, until the first car in the fluid train is full. Then as the the trains continue to pass, people will continue to jump from the blood train and fill all the cars in the fluid train. People will not jump back onto the blood train from the fluid train because remember, they're going in opposite directions. So as the people that jumped on the first car of the fluid train keep going, they're passing the full cars of the blood train going in the other direction.

What would happen if the blood and the fluid were running in the same direction? That would be called concurrent exchange. The salt would still move from the blood, but quickly the concentrations of salt within the blood and the fluid would become the same and there wouldn't be any net gain or loss of salt in either the blood or the fluid. Pretend those trains are now running in the same direction, and people jump onto the fluid train, but then they see open space in the blood train and jump back. Since there will always be space in both the fluid and the blood trains, and they keep running along next to each other, passengers will keep jumping back and forth.

This diagram illustrates the difference between concurrent (top) and counter-current (bottom) exchange. Blue, in this case, would indicate low salinity, and red would indicate high salinity. As for the percentages, there is never "near 100%" absorption of salt from the bloodstream, as that would be as deadly as having too much salt. So take the percentages with a grain of salt.

From Wikimedia commons

The result is a fluid that is actually saltier than sea water. It flows from the gland and is excreted through the nasal passages. Penguins will often look like they have runny noses, but it's really this salty substance coming out their noses. You could, supposedly, say that they pee out their nose, but that would take away some of the mystique from the magestic emperor penguin, wouldn't it?

Immature jokes aside, this gland allows penguins to consume massive amounts of salt, and still be healthy. Considering how high sodium intake contributes to heart disease, maybe penguins could unlock the biotechnology of the future to allow us to have our salt cake and eat it, too!

Reference:

John Sparks & Tony Soper. (1987). Penguins. Facts on File, Inc. 460 Park Avenue South, New York, NY.

Neuromagicology: At the Intersection of Art and Science

We all know how the cameras in our phones are only so good. The photos look grainy and the colors washed out. Compared to the naked eye, phone cameras don't seem to compare.

Well actually, the camera in your smartphone is 2 1/2 times better than your eye! In other words, if the resolution on your phone camera is 5 megapixels, the processing power of your eyes roughly equates to about 2 megapixels. But then, how is it the world around you looks so much sharper, richer, and full of color than the photos on your camera roll? It's because you have something your phone can't even begin to emulate, the brain.

Don't believe me? Hold your arms straight out in front of you. Put the tips of your thumbs together with your index fingers pointed up towards the ceiling, so you're making mirrored L shapes, or one big U shape. Now close your left eye and look at the tip of your left index finger with your right eye. While looking at your left finger tip, focus your attention on your right finger tip. Did it disappear? If it didn't, wiggle it around a bit, and you'll see what I mean; you'll notice that it suddenly vanishes from sight.

That's because your right finger is sitting squarely in the blind spot of your right eye. There are no light-sensing photoreceptors there because that's where all the fibers that make up your optic nerve converge. It has been there all your life, yet you don't notice it until an illusion forces you to. You might have noticed that instead of your finger where it should have been, you just saw the wall or the computer screen or whatever your finger was in front of. What's going on here is the brain is "filling in" that blindspot with the stuff around it. Kind of like the clone stamp tool does in Photoshop.

Illusions reveal the "supreme achievement of the brain"

For a long time, illusions have been thought to be the tools to reveal the limitations of the visual system and show where the brain "got it wrong." Neuroscientists Stephen Macknik and Susana Martinez-Conde see it differently. They think illusions really reveal something special, magical even, about the brain. "This is one of the supreme achievements of the brain," says Stephen, "The brain has actually evolved these processes that are illusory for the purpose of improving vision."

Not only do these illusions show us the nature of our visual experience, but they can also tell us something about consciousness. Consciousness is the first person experience of your life in the world, and it is home grown in your brain. Your senses interact with the outside world and send electrical signals to your brain to make sense of them, but when you look at these sensory systems, "you realize that the information going [to the brain] is really quite deprived." When so little information goes in, the brain has to fill in the details. The so-called conscious part of your brain comes from a separate group of neurons that takes information from your sensory and cognitive systems, your memories, your attention and other systems, and cobbles it together to make a simulation of reality. As Stephen puts it,

That simulation of reality is the only thing you've ever interacted with, it's not that the real world isn't out there--it is--but you've never been there. You've only ever interacted with this simulation of reality that's put together from sparse information from the outside world and the rest is essentially confabulated, just like that blindspot is a confabulation of sorts.

From illusions to magic.

Stephen and Susana are very interested in how our attention and awareness, through the visual system, can be manipulated and what that manipulation says about the process--or confabulation--of consciousness. Illusions can certainly help, but they really only pertain to vision, not awareness and attention in particular. But while organizing a conference for the Association for the Scientific Study of Consciousness in Las Vegas, a little magic happened for Stephen and Susana.

They were brainstorming on how to generate public interest in the topic of consciousness, and they realized that they needed to study the artists of attention and awareness. But who would that be? "Finally it got through to us, Las Vegas spoke to us directly. It said, 'Magicians are the performance artists of attention and awareness.'"

Things took off from there. Stephen and Susana have worked with some great names in magic, like James Randi, Penn & Teller, and Apollo Robbins. Magicians, in the pursuit of bettering their art, have come up with some great theories about how the brain works that neuroscientists have yet to test in the lab. Having these theories before you start to research can also take years off the research process, and really help advance the field of awareness, cognition, and consciousness.

The intersection of art and science

Susana focuses her research on eye movements. There are two different types of eye movements, saccades (which I talked about before) and smooth pursuit. To see the difference. hold out your thumbs in front of you and look at your right thumb. Now try to move your eyes in a line from your right to your left thumb, and you'll notice that you can't do it. Your eyes seem to "skip" along a line to your left thumb. That skipping from point A to point B is called a saccade. Now look at your right thumb as you move slowly to your left, and now you can follow it smoothly, hence "smooth pursuit." So we've just demonstrated to ourselves that smooth pursuit eye movements are involuntary. Now for the Magic.

Apollo Robbins is a professional thief. His act involves very close-range sleight of hand where he pick-pockets from people right before their eyes. Through his art, he noticed that if he moves his hand in a straight line from someone's pocket, people will look at where the hand is going to go, and then immediately back to the pocket through saccadic movement, and that this is a good way to distract someone, or trick them into thinking that he stole something from that pocket when he really didn't. But when he moves his hand in an arch people have to use smooth pursuit to follow his hand, and they don't look back to the pocket at the end.

Apollo's observations led Susana and Stephen to think that perhaps smooth pursuit and saccadic movements affect attention differently, and prompted them to do a study. They found that with straight arm movement away from the pocket from which an item was "stolen," the attention of the thief-ee is directed through saccadic motions from the pocket to Apollo's hand, making the pocket the last place where the thief-ee had their attention, and thus they look back at it. But smooth pursuit eye movement directs attention to the hand as it moves away from the pocket, and there's enough time in between that the pocket isn't the next logical point of attention anymore.

And that isn't the only example, either. Magicians will "use humor in order to, basically, get away with magical murder. If they get people to laugh, their attention is suppressed." When you think about it, this might seem obvious, but there actually isn't any literature in neuroscience on the emotional modulation of attention. Studies on PTSD and anxiety get at the idea, few have looked at the effect of emotions other than fear on attention.

Sleights of Mind

In their book, Sleights of Mind: What The Neuroscience of Magic Reveals About Our Every Day Deceptions, Stephen Macknik and Susana Martinez-Conde explore just that. They look at how magicians intrinsically understand the mechanisms of our attention and awareness and what their manipulation of those mechanisms can tell us about how our brain constructs our sense of reality from sensory stimuli.

Not only is this book very educational, but it's fun! Sleights of Mind is just as much about magic as it is about neuroscience. It's a great read for anyone, regardless of their background in science, who wants to know more about the brain and how it can be hacked. To order the book, and see some really awesome videos, illusions, and more, visit sleightsofmind.com!

The Advantage of Being Cute

Most people would agree that babies are pretty damn cute. Put a grown man or woman in a room with an infant, and all bets are off, that baby is getting 100% of that man or woman's attention. Wild horses could not stop most people from cooing a baby, yet we don't usually question why. The truth?

Carolyn McGraw

That baby is pretty much helpless on its own, so if it's going to survive, it needs lots of attention from adults. Until it gets to the point where it can walk and talk on its own (and then some), the baby is going to lure you into caring for it with those adorable chubby cheeks and wide eyes full of wonder.

Ethologist Konrad Lorenz first put forth the idea that the typical cute baby, with a large head, round eyes, small nose and mouth, elicits a caregiving response from adults, and even suppresses aggressive behavior.  These features, known as a baby schema or a Kindchenschema, are a pretty useful thing for a baby to have. However, until recently this hypothesis was a bit shaky. Most studies that looked at people's responses to infantile adorableness used line drawings or unmanipulated photos of babies that could not control for other aspects known to affect emotional responses such as facial symmetry.

With the help of Photoshop, researcher Melanie Glocker and her team at the University of Pennsylvania created a situation where participants would only see differences in the baby schema of infants and be able to rate their cuteness and how much they desired to care for the babies. They took pictures of babies and created three photos of each baby: one undoctored, one changed to maximize the baby's cuteness, and one to minimize it.

In the center, the unmanipulated photo. With the less cute manipulated photo to the left, and the cute one to the right.

Then the researchers got a group of 122 undergraduates and split them into two groups: one group would rate each photo's cuteness, and the other would rate how much they wanted take care of the baby in each photo, both on a 1-5 scale.

As expected, participants rated the "high cuteness" manipulated photo as being significantly more cute than both the undoctored and "low cuteness" manipulated photos. Participants in the caregiving group also rated themselves as having a stronger desire to take care of the cuter babies.

Other research has suggested that the emotional impact of cuteness is influenced by female sex hormones, so the researchers hypothesized that women would be more strongly affected than men by cuteness. In fact, men and women rated the cuteness of babies pretty equally, and both men and women had a stronger desire to take care of cuter babies than less cute babies. However, women rated their desire to take care of babies of all cuteness higher than the men did. The researchers suggested that this could be a cultural as well as biological predisposition as historically in many cultures, women have generally been the primary caregivers of children.

The researchers also mentioned that before the rise of the nuclear family, childrearing was often done with the cooperation of friends and extended family. This could explain why both men and women have a strong desire to take care of babies, and why this desire extends to babies that they are not related to. After all, we are social animals, so we have to look out for each other!

Reference:
Glocker, M.L.; Langleben, D.D.; Ruparel, K.; Loughead, J.W.; Gur, R.C.; Sachser, N. (2009). Baby Schema in Infant Faces Induces Cuteness Perception and Motivation for Caretaking in Adults. Ethology 115(3): 257-263.

Special thanks to my wonderful and wonderfully talented friend, Carolyn McGraw, for making that awesome Admiral Ackbar drawing! You can see more of her stuff here and here.

Blindsight and Consciousness, what can we learn from the blindsighted?

If there were ever a perfect example of an oxymoron, the term blindsight would be it.

Other than the best oxymoron ever, what is blindsight?  Alan Cowey, in his 2010 review article, The blindsight saga, describes it as such:

It is the ability of patients with absolute, clinically established, visual field defects caused by occipital cortical damage to detect, localize, and discriminate visual stimuli despite being phenomenally visually unaware of them.

In simpler terms, it's the ability to sense the presence of objects in one's visual field without consciously seeing them the way normal sighted people do.  While it would be a stretch to call blindsight a superpower, the visual capabilities of a person with blindsight could be considered akin to those of Dare Devil.  Blindsighted people often are able to identify visual stimuli, although they deny having a conscious experience of actually seeing anything.

In this video, a blindsighted patient is able to navigate a field of obstacles successfully, even though he can't see them.

How does blindsight happen?  It is a fairly unique condition; not all people who are blind possess blindsight.  It occurs in patients who become blind in part or all of their visual field after suffering damage to the primary visual cortex, known as V1.

The primary visual cortex (V1) highlighted in yellow.  The bottom view is from a mid-section of the brain, the top view is from the outside.  In both views, your eyes would be on the left.  Source.

Becoming totally "cortically blind," as is the case for the patient in the video above, is actually pretty rare (thankfully), so most patients with blindsight are only blind in part of their visual field, while the rest of  the field remains normally sighted.

A controversial subject

Blindsight has drawn a lot of controversy among researchers.  Since the hallmark trait of blindsight is responsiveness to visual stimuli without the conscious experience of perceiving it, it makes animal studies a little difficult.  You can observe where a cortically blind animal turns its attention when presented a stimulus, but you can't ask it if it actually saw anything.  So researchers interested in getting at the question of what people with blindsight actually do or do not experience have a relatively small pool of subjects they can perform research on.

Then, of course, there's the fact that whatever blindsighted patients report as their experiences of blindsight must be taken with the grain of salt as all experience is subjective.  Some patients report that, even though they didn't see anything, they have a feeling that "something happened."  The question, then is, is this feeling essentially visual in nature?  Did it come about due to light scattering from the stimulus into their seeing field?  Or did the subject report a feeling of something happening because that's what he or she felt that the researchers were looking for?  The answers to these questions have proven to be extremely difficult to tease apart.  Regardless, the fact that some patients have "feelings" when presented a stimulus and others do not requires that blindsight be split into two categories: type 1, no awareness at all; and type 2, awareness without visual experience.

Even in patients with type 2 blindsight, the awareness of the stimuli isn't always consistent.  But we can still learn something here.  In one task, patient GY was asked to discriminate between the presence or absence of a stimulus and then wager money on his answer.  Incorrect wagers would be subtracted from his winnings, thus prompting him to only wager high when he was very confident of his answer.  When he felt that he was aware of the stimulus, despite not seeing anything, he wagered high and was correct more than 90% of the time.  When he didn't report any awareness, he wagered low, as would be expected.  But he was correct more often than could be explained by chance, suggesting that even without awareness, he was still able to perceive visual stimuli.

Total cortical blindness

Let's re-visit the patient in the video, TN.  After successive strokes, TN's primary visual cortex was completely destroyed, as was later verified by both structural and functional MRIs.  Something helpful at least came of TN's misfortune, in that he gave researchers De Gelder et al a rare chance to study a person with total cortical blindness.  The video above is truly astonishing because, at first glance, it looks like he is able to avoid obstacles without the use of a cane or any outside guidance.

Nevertheless, this video is not without its critics.  The first that springs to mind is echolocation, a capability that has been shown in other blind people.*  The researchers recognized that this could not be ruled out, but many critics of the research suggested that not enough attention was paid to the possibility of echolocation anyway.  Other critics say that TN could have been unconsciously processing auditory signals from the researcher shadowing him (to make sure he didn't stumble or fall), and that those aided in his navigation.

TN's contributions to blindsight research don't just end with that video.  TN also demonstrated affective blindsight, or the ability to discriminate between emotional stimuli in a physiological sense.  Researchers Gonzalez-Andino et al showed TN pictures of various facial expressions and monitored his brain activity via an EEG.  Without any awareness of the stimuli whatsoever, the researchers were able to localize changes in the electrical activity of parts of the brain associated with emotional stimuli, such as the right amygdala, in TN.  In these trials, TN was also not asked to guess at the nature of the stimuli, either, so the results suggest some perceptual ability without any conscious awareness at all.

Conclusions: what blindsight can tell us about consciousness

It is extremely important to note that all studies on blindsight and consciousness are done with very small sample sizes.  Most studies are case studies that focus on the abilities of only one patient.  Because of this, everything that we can say about blindsight must be taken with a grain of salt.  There simply aren't enough subjects with blindsight to tell us very much with any certainty about the nature of consciousness and vision.  Nevertheless, some results are so provocative that they can at least give us clues and ideas about where consciousness in vision lies in the brain, and can give us leads for further and more focused studies in the future.

It has become clear that blindsighted patients' vision is certainly unlike normal vision, and obviously unlike total blindness.  There is definitely some ability in patients to perceive objects, even if the true nature of that ability remains murky.  And it's the murkiness of that ability that makes blindsight so tantalizing to researchers interested in the neural mechanisms of consciousness.  How can one see without actually seeing?  That is the big question.  The visual pathway is certainly very complex, but the blindsighted just may be able to tell us what aspects of that pathway give rise to the conscious experience of sight, and wouldn't that be so cool?

*While looking for the video about Ben Underwood, I found out that just a few years after the original news spot was filmed, he sadly died of cancer.  You can read more about him and his life here.

References:

Cowey, A.  (2010).  The blindsight saga.  Experimental Brain Research 200:3-24.

de Gelder, B.; Tamietto, M.; van Boxtel, G.; Goebel, R.; Sahraie, A.; van den Stock, J.; Stienen, B.; Weiskrantz, L.; Pegna, A.  (2008).  Intact navigation skills after bilateral loss of striate cortex.  Current Biology 18,24:1128-1129.

Gonzalez-Andino, S.L.; de Perlata Menendez, R.G.; Khateb, A.; Landis, T.; Pegna, A. (2009). Electrophysiological correlates of affective blindsight.  NeuroImage 44:581-589.