Tuesday, March 27, 2012

Seeing Cells: Nissl and Golgi together at last

Seeing through a glass darkly (Bob Jacobs, Colorado College)
The quest to visualize cells is a long and continuously evolving one. 

We have previously discussed how neuroscientists use calcium to watch cells in action, but a surprising amount of information can be gleaned from simply staining fixed (inactive) cells.

There are so many ways to stain fixed cells that I have to write this in parts.  First we'll discuss two of the oldest techniques still commonly used, the Nissl stain and the Golgi stain. 

One of the earliest techniques to allow for the visualization of neurons is the Nissl Stain.

Nissl stain of visual cortex (source)
The Nissl stain colors the cell (purple if you are using cresyl violet) because it reacts with nucleic acids (which make up DNA and RNA) in the nucleus of the cell and in the endoplasmic reticulum. 

The Nissl stain reacts with most of the cells in a brain slice (both neurons and glial cells), so it is not great for seeing the detailed morphology of a single neuron. However, it is great for seeing the cellular patterns of a particular brain area.  The image above clearly shows the different layers of the visual cortex.  Layer 1 has almost no cells, but layer 4 has tons. 

This technique can be used to visualize the results of a certain mutation or drug treatment on the brain. It is often also used as a control experiment to confirm that a treatment did not kill cells or damage the brain. 
(side note: If you want to do this stain yourself, numerous protocols are available online)

In contrast to the Nissl stain which stains almost all the cells, the Golgi stain impregnates only a few of them.
Golgi stain of Hippocampal neuron (Bob Jacobs, Colorado College)
The Golgi stain works by starting a silver chromate reaction in random cells.  It is not known why a certain cell would undergo the reaction while a cell right next to it would not. The result is that the morphology of the cells can be clearly seen without contamination from nearby dendrites from other cells. 

This technique can be used to test whether a mutation or drug treatment alters the growth of cell dendrites. 

(There are protocols online for this stain as well)

A group at Leicester University in the UK has developed a protocol that combines the Nissl and Golgi stains, so you can have the best of both worlds.
Pilati et al., 2008 Figure 3

Using this technique, they were able to more accurately characterize the morphology of neurons in specific areas of the brain.  They also found that the Nissl stain underestimates the soma size compared to the Golgi stain.

© TheCellularScale

ResearchBlogging.org Pilati N, Barker M, Panteleimonitis S, Donga R, & Hamann M (2008). A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 56 (6), 539-50 PMID: 18285350

Sunday, March 25, 2012

Reasons for Reason Rally

Reason Rally: a reason to stand in the rain
(I took these pictures)
On March 24th, 2012 there was a Reason Rally in Washington DC.  The idea was to celebrate reason, science, and the atheist community. Despite the rain, free thinkers from all over the country participated in numbers to rival Glen Beck's rally the year before last.  There were plenty of clever signs (my favorite: "let's have a moment of science"). Some people dressed like Jesus.
Or Jesus riding a dinosaur:
not quite Mario and Yoshi

 Or wore flying Spaghetti monster hats:
noodles for your noodle

While entertaining, these signs and costumes were not the main point of the Reason Rally.
Here are some of the main messages from the first half of the rally.

1. Separation of church and state (Jessica Ahlquist, Taslima Nasreen)
This is by far the most important message of the atheist movement right now.  With Rick Santorum publicly saying that JFK's statement "church and state should be completely separate" made him want to vomit, the threat of theocracy has become all to real. 

Jessica Ahlquist, a highschooler who won a lawsuit to have the prayer banner removed from her school spoke early in the day about the way non-atheists in her school treated her and how a congressman even called her 'evil little thing'.  It is unfortunate that lawsuits like hers are needed to preserve the freedom of religion. 

Taslima Nasreen, an exile from Bangladesh, really drove home the dangers that can come from not maintaining a separation of church and state illustrated through Islam.  She explains that you can be arrested for simply saying that you do not believe in god in her home country; and that the religious leadership of her country allows policies that oppress women as 'slaves, objects, and baby-making machines' It is easy for even religious Americans to see that the Islamic theocracies are not compatible with equal rights, freedom, or democracy. It is frustrating when people don't see that a christian theocracy would be equally oppressive. 

2. Atheism is not a religion (Bill Maher, Tim Minchin)
Another important point is that atheism is not just one of several religious choices. 

"Atheism is a religion the way abstinence is a sexual position" Bill Maher
Atheism and the following of 'reason' involves a fundamentally different way of thinking than a religion.  That is, skeptics and atheists use evidence and science to form their beliefs and are willing to change those beliefs if new evidence appears.  Religion on the other hand is based on believing something without (and often in spite of ) evidence. As Tim Minchin says in his poem "Storm":
"Science adjusts is views based on what's observed.
Faith is the denial of observation so that belief can be preserved."

Watch the whole poem with animation accompaniment here:

3. Skeptics are not Cynics (Michael Shermer, The Amazing Randi)
The heading says it all.  Being skeptical does not mean you are cynical and see the bad side of things.  Skepticism is simply not believing something until you have a reason to.  You can be an optimistic skeptic, hoping for the best, hoping a new treatment will work, but not believing that it works until you see evidence.  I would argue that scientists are almost all (and should be) optimistic skeptics.  Scientists wouldn't do their experiments if they didn't expect something out of them. 

Similarly, skeptics are not unhappy, and scientists are not incapable of awe. As illustrated in my favorite xkcd comic of all time, scientists see deep beauty in the world as it is. 

The natural world is astounding and awe-inspiring, why gild the lily or perfume the violet with the supernatural (summary of Tim Minchin).  You don't need to think that god created it to see the beauty in a flower, the wonder of a neuron, or the delicacy of the fly proboscis.
(source) (I did not take this picture)
 I had to leave the rally early, so I don't know how the second half shook out, leave a comment if you have something to add. 

© TheCellularScale

Friday, March 23, 2012

How to Tell a Story: Science Edition

Recently I watched a really great Ph.D. dissertation defense, and it got me thinking:
What was so great about it?

While there are many factors that go into a good presentation (and you can read all about them at Neurodojo: the Zen of Presentations parts 1-1bazillion), but I think there is a single golden rule after which all other rules are secondary.

Use as few words as possible.  

This doesn't mean 'say as little as possible'.
It means say a lot, but make your points using the minimum number of words necessary.

Aside from the obvious cutting out 'ummms' and 'likes' that can be distracting, simply saying what you are going to say without caveats and without extra phrases is always the best way to go.

Here's a secret about me: In my pre-neuroscience life, I spent 2 years teaching special education at an elementary school.  This job involved herding distracted children and trying to teach them things in the most interesting and engaging way possible. The idea being that if the students are engaged with the lesson they will be less likely to throw their pencil box across the room or knock their desk over (both unfortunately frequent occurrences).

One infinitely transferable lesson I learned was 'how to tell a story'. 

The method was something like this:

1.  Read the story to yourself.
2. Write the story down in 10 sentences.
3. Write the story down in 5 sentences.
4. Write the story down in 1 sentence.
5. Tell the story at the level of detail appropriate for the situation. 

 Simple, right? And obviously applicable to scientific communication. This is a step by step method for crafting a good elevator story.  It is also something everyone should do before they make a poster, give a presentation, or even write a paper.  In fact, you should stop what you are doing right now and try to write down your dissertation or current project in 10, 5 and 1 sentence.

Becoming an expert on something is not simply knowing all the details about it.  It's also knowing which ones are critical to the main point and which ones are not.

© TheCellularScale

Wednesday, March 21, 2012

How animals, Shrek, and Yoda stimulate your neurons.

Is CellularDog thinking 'yum'? or 'aww'? (I took this picture)
(and, yes, sometimes I wear ugly Christmas pants)
Recent studies have found that specific cells in the human brain respond to specific things.  And I don't just mean those vision neurons that respond to lines or circles that you learned about in psychology 101.  There are neurons in your brain that selectively respond to concepts (like celebrities, faces, and animals).  Let's talk about animal cells...(that is human cells that respond to pictures of animals.)

Studies recording from cells in the human brain can be conducted on patients who need electrodes implanted for other reasons (such as epilepsy monitoring). Testing neuronal responses in 41 such patients, Mormann et al., (2011) found that certain cells in the right amygdala responded to pictures of animals (They also showed pictures of people and places, but these neurons only responded to the animal pictures). 
Mormann et al., 2011 Supplemental Figure 2a
Here are some of the pictures that they showed the patients.  The blue dashes below each picture represents each time a particular neuron fired.  As you can see this particular neuron fires a lot when a picture of an animal is shown, but is not so excited by buildings or Brad Pitt. 

While there were cells that responded to all animals presented, some cells only responded to certain animals, like this one, which prefers mice and rabbits, and doesn't respond to rhino, tiger or eagle. 

Mormann et al., (2011) supplemental figure 2b

They also tested pictures of two 'ambiguously animalistic' characters: Shrek and Yoda. Many cells in the right amygdala that responded to animals also responded to pictures of Shrek and Yoda, so they classified them as animals...
animal, mineral, or vegetable?

A side note on scientific practice:

Is this correct scientific practice to classify something because it fits in with the rest of your data?

No way, Jose.
They should have done all their statistics without those two 'ambiguous' pictures because their classification was based on the very result they were investigating.
(To be fair, they apparently did test everything whithout shrek and yoda and it "did not alter any of the reported findings")

but, here's another way to look at it:

some pseudo-data
I want to do a study to test whether people like red or blue objects.  So I line up a bunch of red and blue objects on a table and have people come pick out five of their favorite.  I record what fraction of the favorite items is red and what fraction is blue.  But just for fun I throw in some purple objects.  Then I look at all my data and see that there were more favorite objects that were blue than red, and I see that the people who picked a lot of blue objects also picked a lot of purple objects. So I decide to classify the purple objects as 'blue' because the same people who picked blue picked purple.
The finding that blue is preferred over red is not altered, because people preferred blue already (see pseudo-data), but it's better to report the findings without the a posteriori classification of purple as blue. 

So yeah, no. Don't do that.

Ok back to the study, which despite this 'Yoda and Shrek are animals a posteriori' thing, is still pretty awesome. 

The Big Question: What does it mean that these cells respond only to pictures of animals?

In the supplementary discussion, the authors point out that the amygdala neurons fire 300-400 ms after the picture is presented.  They say that this timing is almost certainly after the identification of the picture would have taken place.  That mean that these neurons are probably not the ones telling you 'this is a tiger', or 'this is a spider', but instead might encode a response to knowing that it is a tiger or a spider. 

Are these neurons coding for that "awww" feeling that you get when you look at cute things? The authors say 'probably not' because the spider is not really an 'awww' inducing image. (Though given that yoda and shrek stimulate these neurons, would pictures of babies, stuffed animals, or other abstractions stimulate them as well?)

Are these neurons coding for a fear response? This is the amygdala after all. But again the authors say 'probably not'. 
"Previous studies have implicated the human amygdala in fear- and threat-related processing. The animal images that elicited neuronal responses in the amygdala contained both aversive and cute animals, and we found no relationship between amygdala responses and either the valence or arousal of the animal stimuli."
In the end, they really don't have a satisfying explanation for what the amygdala, and even more interestingly only the right hemisphere's amygdala responds selectively to animals. 

"A plausible evolutionary explanation is that the phylogenetic importance of animals, which could represent either predators or prey, has resulted in neural adaptations for the dedicated processing of these biologically salient stimuli."
So basically they say, maybe neurons in the amygdala tell you 'this is animal-like, so pay attention' because of 'the evolutionary salience of animals'.  This might be true, but it's a pretty thin and un-meaningful explanation. 

It will be difficult to conduct more detailed experiments because these are human subjects with electrodes implanted in specific places for epilepsy monitoring.  That means, you are not going to be able to test what cells are synapsing onto these animal cells or where these cells send their signals.  But even with these limitations, interesting advances can be made by testing a wider variety of pictures to the subjects, to see how specific these cells can actually be.  (What if the animal is small and in the corner of a picture, where do babies or children fit in,  etc) 

© TheCellularScale

ResearchBlogging.orgMormann F, Dubois J, Kornblith S, Milosavljevic M, Cerf M, Ison M, Tsuchiya N, Kraskov A, Quiroga RQ, Adolphs R, Fried I, & Koch C (2011). A category-specific response to animals in the right human amygdala. Nature neuroscience, 14 (10), 1247-9 PMID: 21874014

Saturday, March 17, 2012

New Mass Effect 3 Endings

In non-cellular news, I just beat Mass Effect 3 and had some thoughts.

Femshep or noshep
First let me say that I loved this game and still stand by my statements that everyone should play it

There has been a lot of hoo ha about the different (barely) endings available in Mass Effect 3. Having just finished it, I have to say I pretty much agree. There is a fantastic (and lengthy) post at Game Front by Ross Lincoln that explains exactly what is disappointing about these ending choices. At Kotaku you can watch a sample of the 16 available endings and see for yourself (how similar they are). 

So yeah, I do agree that the ending is a little disappointing (for pretty much exactly the reasons Ross Lincoln points out in his article).  It was a huge info-dump on themes and topics not essential to the main plot of the game, and that seriously just didn't make sense.  Bioware should have hired Brandon Sanderson to write the ending of this game because that guy knows how to wrap sh*t up.   

so yeah, disappointing, but the end of my world, no.

Would I buy a new downloadable ending from Bioware? no, probably not.  Will I complain endlessly on twitter that Bioware 'owes us' a better ending? no, I think they delivered an amazing game and  I had a great time playing it. Am I going to write my own endings on my blog? ...Yes...

Here are some endings divided up into categories to make everyone happy:

1. Sad, but worth it endings

a. Control the Reapers:
Shepard dies, and you see the reapers leave.  Then you should see Shepard in that digital-shape that the kid is in at the end, implying that Shepard takes the place of that kid as the reaper-controller.  She becomes god, basically.  Also you should see Shepard looking down at some of her teammates (like Garrus, who she specifically tells she will 'watch over' if she dies and he doesn't) 

b. Destroy the Reapers:
Shepard dies, along with all synthetics.  So you see a scene on Rannoch where the Quarian and Geth are working together to rebuild a new world (if you saved the Geth), and all of a sudden all the Geth just fall over dead.  Sad, but interesting.  Also, you see EDI die because she is, of course, synthetic, and you see Joker freak out.  Also very sad.  Your love interest from the game should find out your are dead and be miserable.  But then you see some great scenes of the new Krogan utopia (if you cured the genophage) with little krogan babies (awww), and Wrex being a dad with his kid Mordin, how cute right? This is the Galaxy that you sacrificed yourself and everyone else to save. Maybe a scene of Kolyat praying, Jacob and his new family, Jack and her students, Miranda laughing with her sister... you know nice stuff that lets you know It was worth it

c. Synthesis:
To be honest, I liked this ending as it was.  I like the Joker and EDI =Adam and Eve look of the whole thing.  It's a good ending to support the idea that there is a completely new age starting, one where synthetics and organics are merged.  However, the third person should NOT walk out of the normandy though, seriously why the 3rd wheel?

Joker and EDI = Adam and Eve (Eden Prime Prime?)

2. Happy, everything is perfect endings

I am glad that Mass Effect 3 didn't go the cheesy route of everything being perfect.  A happily-ever-after just doesn't fit The Shepard.  But it is fun to think about, so here are some scenes that would make delightful endings for the disney-lovers out there.  In each ending, Shepard lives, her/his love interest lives, earth is saved, and the galaxy is back to 'normal.' The endings mostly involve babies:

Asari baby, awww.  (source)

a. Liara: Little babies in blue running around Thessia, messing with mommy's shadow broker VI. 
b. Thane: Yeah, he's dead, but a scene of shepard visiting his grave or seeing his son wouldn't be horrible.  Also, everyone wants to go to the Hanar-Drell homeworld and cure Keprel syndrome.
c. Garrus: ok no babies here, just some totally fun hanging out and being happy together scene of Shepard and Garrus on a newly rebuilt Palovan. 
d. Kaiden: Some super sweet scene where Kaiden and Shepard look out at the sunset from their porch-swing on Kaiden's land on the Sun Coast.  Also...Shepard's pregnant.
e. Jacob: Just like Kaiden's ending but with Jacob.
f. Ashley: Just like Kaiden's ending but with male shepard and Ashley's pregnant.
g. Tali: Retiring to a beautiful house on Rannoch, you get to see her face! and you have a geth nanny to help out with the kids. 
h. Miranda: no babies (if you are astute, you may have read the shadow broker's intel explaining that she can't have kids), but you see her and Shepard being happy together somewhere beautiful just like all the other endings. 
i. Jack: I can't really think of anything good here, but she'd be happy.

ha, ok my teeth are sore from all this sugar. 

3. Really Sad Ending

Another possibility is that a huge portion of your team dies, but Shepard her/himself doesn't.  It's pretty clear that Shepard is the only one to survive that ending blast, so the two people you bring with you to the last fight should both die.  If one of those is your love interest for the game or if one is EDI, there should be a sad scene of you lonely and wondering if it was worth it, and/or of Joker freaking out.  The main theme of the whole game is what is worth it? You tell the Illusive Man that he "Sacrificed too much" but maybe you did too. 

4. Epilogue-style endings

Another idea entirely, that would not be too much work for Bioware in the animation department, would be to expand the epilogue scene with the grandfather and kid to actually 'show' the legend of The Shepard.  As in have a story-book style book that you can flip through at the end detailing Shepard's major choices throughout all three games. Just some stylized drawings (I'm thinking Fable here) and text.

Story book Thane from Dashiana

Everything could be taken into account here and basically every playthrough could have a slightly different story at the end.  It would also be cool if some clever writer could put in little interesting twists that could represent the story being destorted as it is passed down through generations.  For example, if you choose the Krogan over the Salarians on Tuchanka, the story might show the Salarians as bad guys with their 'antennae' turned into devil horns or something.  Similarly if you support the Salarians, the Krogan would be depicted as dangerous and evil. 
Anyway, I think this story book ending would be the best solution because it would be easy enough for bioware to put together, it would be different depending on the choices made, and it would be satisfying to see that your decisions made a difference in the future mythology of the galaxy. 

© TheCellularScale

UPDATE 7/2/12: Thank you Bioware for following my advice and adding the story-book style epilogue to each ending! I was really delighted that in the destroy ending there were no geth and no EDI and that the Quarians were still in their suits. The ending choice now has actual consequences, and is therefore much more satisfying.


Wednesday, March 14, 2012

Plant Neurons? Sensation and action in the Venus Flytrap

Plants are more electric than you might think. 
(Venus Fly Trap by Nick Ford at nickpix2012)
While they don't have neurons in the proper sense, they have sensory receptors, ion channels,  action potentials, and can process information. One of the most remarkable feats of plant information processing occurs in the venus flytrap. 

The venus fly trap is remarkable among plants because it has very fast and very specific information processing capabilities.  It can sense changes in its environment and act upon its sensations quickly. 

Here's how it works, illustrated by 3 fascinating studies. 

1. Sensation: The venus flytrap has 3 little hair-like protrusions (see above photo) on each side of the 'mouth'.  These 'trigger hairs' contain mechanosensory cells which activate when the hair is moved.

Benolken and Jacobson, 1970 Figure 1. A trigger hair set up for electrophysiological recordings.

In order to see what these cells are actually like, Benolken and Jacobson used electrophysiology methods (similar to the ones used in animal neurons) to record the cells' electrical signals during mechanical stimulation. 
up close image of a trigger hair.
The sensory cells are at the indentation
point near the bottom. (source)

They found that the primary sensory cells were right near the base of the hair where there is a distinct indentation.  In other words right where the trigger hair would bend if a delicious fly bumped into it.

They also measured the force needed to stimulate these cells.  Interestingly in more mature plants, the trigger hairs are stiffer and require more force to activate the mechanosensory cells. (Why this would be, I am not sure. Maybe larger prey hits the trigger hairs harder, and the larger older traps don't want to bother with puny meals.)

When enough of these sensory cells are activated, they trigger the second step in the process, the action potential.

2. Information travels from the base of the trap through the two sides of the 'mouth' and makes it close.

Here is where it gets tricky.  I couldn't find any detailed information on how the sensory cells are connected to the base of the trap (also called the midrib).  These sensory cells must 'project' to the midrib, but how these projections are shaped, where they converge, and how they relay their signal to other cells is a mystery to me.  (If you know or have a reference please post it, I am curious about this missing step.)
Electrodes implanted in the lobes and
midrib of the venus flytrap.
Volkov et al., 2007 Figure 6
However, once the information gets to the base of the trap, it takes on the form of an action potential which travels through each side of the leaf.  To investigate this action potential, Volkov et al. (2007) placed silver-chloride wires directly into the midrib and lobes of a trap and record the electrical transients.  They find that when they stimulate the hairs, an action potential can be recorded through these wires. They also find that by putting current directly through the wires, they can cause the trap to close even without stimulating the hairs.
Action potential from a Venus Flytrap (Volkov et al., 2007)

They are able to inhibit this action potential by applying ion channel blockers to the soil of the plant 2+ days before the experiment.  The application of TEACl (a potassium channel blocker) prevented the trap from closing when the hairs were triggered and when the electrodes were directly stimulated.  The application of calcium channel blockers caused the trap closure to be much slower.  So the information traveling step requires potassium and is pretty reliant on calcium too.  So once the action potential is triggered, how does that actually make the trap close?

3. Trap Closure 
There are several theories about how the trap actually closes. Some involve actual cell growth, but Foterre et al., (2005) show that the trap can close based mainly on mechanical principles. 

Foterre et al., 2005 Figure 1b. UV sensitive dots all over flytrap surface
To visualize the specifics of trap closure, Foterre et al. paint uv-sensitive dots in a grid on each trap lobe. This technique is surprisingly like what this person did using white-out to test their own garden of flytraps.  Basically Foterre et al. show that there is a biophysical trigger that changes the curvature of one part of the plant, but that as soon as that curvature is changed the rest of the process is a passive response based on mechanical principles.  That is, the 'snapping' closed has a passive component that can be modeled computationally as a thin elastic sheet.  They summarize it nicely in their last paragraph:

"Upon stimulation, the plant 'actively' changes one of its principal natural curvatures, kappaxn, the microscopic mechanism for which remains poorly understood. Once this change occurs, the geometry of the doubly-curved leaf provides the mechanism by which elastic energy is both stored and released, and the hydrated nature of the leaf induces the rapid damping that is equally crucial for efficient prey capture. A single geometrical parameter (alpha) determines the nature of closure: if alpha less than or equal to alpha c approximately 0.8, the leaf closes smoothly, and if alpha > alpha c, the leaf snaps rapidly. This ingenious solution to the problem of scaling up movements and speed from the cellular to the organ level in plants, nature's consummate hydraulic engineers, shows how controlling elastic instabilities in geometrically slender objects provides an alternative to the more common muscle-powered movements in animals."

So there you have it, everything you ever wanted to know about the Venus Flytrap and then some. Even though the flytrap electrical properties have been studied for hundreds of years, there is so much that is not known. I dare say we know more about the neurons of the mouse brain than we know about the sensory cells in the Venus Flytrap. 

And of course, no scientific phenomenon is complete until someone makes a robot out of it

© TheCellularScale

Benolken RM, & Jacobson SL (1970). Response properties of a sensory hair excised from Venus's flytrap. The Journal of general physiology, 56 (1), 64-82 PMID: 5514161

Volkov AG, Adesina T, & Jovanov E (2007). Closing of venus flytrap by electrical stimulation of motor cells. Plant signaling & behavior, 2 (3), 139-45 PMID: 19516982  

Forterre Y, Skotheim JM, Dumais J, & Mahadevan L (2005). How the Venus flytrap snaps. Nature, 433 (7024), 421-5 PMID: 15674293

Saturday, March 10, 2012

Calcium: for more than just your bones

You have probably heard that calcium is good for your bones, but what you might not know is that your brain can't function without it. 

Broccoli is rich in calcium (source)

We have previously discussed the electrical properties of neurons.  Much like the sodium ion (Na+) and the potassium ion (K+), the calcium ion (Ca2+) can flow into and out of the cell to modulate its electrical activity.

Grienberger and Konnerth 2012, Figure1

Calcium has an even bigger role, however.  When a burst of activity in a particular neuron causes calcium channels to open, the calcium ions rush in and bind to all sorts of molecules inside the cell.  These molecules help adjust the connection between two neurons by helping to strengthen or weaken the synapse between them. 

Because calcium easily binds to many molecules, and because it flows into the cell when the cell is activated, dyes which bind to calcium have made it possible for scientist (and you) to 'watch' neurons fire:

Amazing, right?  When the neurons are activated, the calcium rushes in and binds to the dye and causes the cell to light up. 

If you noticed, it's not just the main middle part of the cell (the soma) that lights up, the dendrites light up too. If you watch very closely you can even determine the direction of the signal. Sometimes it is going down the dendrite to the soma, and sometimes it is going up from the soma out through the dendrite. Being able to see the location of the calcium signal is more specific that just seeing (or hearing) spikes from neural activity (which is a summary of what the cell is doing as a whole, but doesn't differentiate between parts of a neuron). 

A recent review by Grienberger and Konnerth highlights some of the even more amazing advances to calcium imaging.  They explain how, using a light-weight teeny-tiny head-fixed microscope, scientists can now image the activity of neurons inside the brain of a living, moving mouse. 

This is a huge advance because now scientists can see not only that a specific cell is firing when something happens, but can actually watch the activity of different dendrites on a single neuron when that thing happens. 

One of the limitations to using calcium imaging to watch neurons in the intact brain is that light doesn't travel through the brain that well.  So far only the neurons close to the surface of the brain are being imaged.

© TheCellularScale
Grienberger, C., & Konnerth, A. (2012). Imaging Calcium in Neurons Neuron, 73 (5), 862-885 DOI: 10.1016/j.neuron.2012.02.011

Sunday, March 4, 2012

4 reasons why all women should play Mass Effect

Another adventure outside of the 'cellular neuroscience' walls for The Cellular Scale.  Today we are traveling to the land of video games, video games and women. 

Commander Shepard, the most badass woman in the galaxy

Mass Effect 3 is being released in a few days and I thought I would use this time (while my xbox is downloading the free demo) to write about why the world would be a better (or at least slightly more gender-neutral) place if all women played Mass Effect. 

Update: Just beat Mass Effect 3, see my thoughts on the endings here

There are four main reasons people (especially women) should play this video game.

4. it's fun.

This is reason enough to play the game. Mass Effect is a sci-fi video game with some of the best world-building in book, movie or game to date (I expect angry comments bringing up Star Wars, Star Trek or Dune below, but I'm standing by that statement). Mass Effect presents a rich world with a cohesive believable history. You can literally read volumes about each species, each planet, each mercenary group, and each weapon if you are so inclined. There are nuances and details hidden everywhere that subtlety but strongly enrich the game.

A quick summary **SPOILERS**

You play as Commander Shepard (you can choose to be male or female), who is a human in the Alliance military. 

troubled, but handsome
In Mass Effect 1, you have to track down and defeat a rogue spectre, Saren.  He is an obvious bad-guy (the first thing you see him do is shoot his 'friend' point blank), but he does the job. You have to deal with some anti-human speciesism from the alien council, but they are generally on your side. You recruit some companions: a badass soldier in pink, a troubled but handsome biotic, an engineer on her pilgrimage, an ex-cop, an archaeological scientist, and a merc-for-hire tough guy.  Then you go save the galaxy. Upon saving the galaxy your realize that the threat was much bigger than just the one rogue spectre.... which brings us to Mass Effect 2 (in which the shooting-game play is much improved) 

'being perfect is so difficult'
In Mass Effect 2, you have been dead for two years, but are being rebuilt by Cerberus, a company that you only heard about in passing in ME1, but what you heard was bad.  Cerberus is a human-supremacist group and it rebuilt you to help humanity, not the galaxy.  So under the Cerberus logo, you attempt to face the 'bigger threat' that you discovered at the end of ME1. Human colonies are being destroyed, but in a really weird way where everything is left perfectly intact but all the humans are gone.  You investigate these colonies, discover the reason behind these weird disappearances. Of course, you recruit some companions: a woman who likes to complain about being genetically modified to be 'perfect', a troubled but handsome biotic (not the same one), the same engineer after her pilgrimage, the same ex-cop, a killing-addict tattooed biotic, a pod-grown tough-guy, a geneticist/doctor, a morally rigid monastic biotic (or her evil daughter), a negligent father/assassin,  and a robot.  In this game you spend most of your time recruiting these companions and doing 'loyalty' missions for them.  Then you save the galaxy.... and in saving the galaxy, you realize the threat isn't over...which bring us to Mass Effect 3 (in which a cooperative multi-player aspect has been added) 

So the game is fun.  The graphics are good, the action play is fun, leveling up is fun, the characters are great, the story is entertaining, but what really brings this game up a notch from other is the:

3. Complex morality

Like a lot of modern video games, you can make decisions in Mass Effect that have short and long term consequences. In fact, the decisions you make in ME1 effects who you see in ME2 and how you interact with them. Like other games you can become 'good' or 'bad' (Fable and Knights of the Old Republic are some of the games which pioneered this morality system), but in Mass Effect it is called "Paragon" or "Renegade" and it is a little more complex than in the other games.  Paragon isn't necessarily good and everyone likes you, and Renegade isn't necessarily evil and everyone dies.
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Some of the moral dilemmas you face in this game remind me of game theory and morality experiments.  Do you follow the law in all situations or do you break it for the greater good?  Do you kill one to save many, or do you protect your friends and let strangers die? 

The biggest moral dilemma in Mass Effect 1 is when you have to decide between two of your teammates, you don't have time to save both of them.  Who do you choose?

Interestingly, it's not all 'thanks for saving me' from the person you rescue either, they feel guilty and upset because you chose them instead of the other person.  This choice carries over all the way to ME3, where whichever person you saved apparently plays an important part. 

My favorite moral dilemma is in Mass Effect 2 though, because it is related to science!  Your teammate, the geneticist, confesses to you that he took part in producing the genophage, a mutation that drastically reduces the fertility rate in a particularly aggressive alien species.  These aliens previously lived on a very hostile world and the constant environmental threats kept their population low.  However, when they came into contact with other aliens and moved off their hostile world, their population exploded under their new non-threatening conditions.  The geneticist in your group had lead the initiative to infect this alien species with a mutation (yes the fake science gets iffy here) that would decrease the fertility rate in females to like 1%.  In your discussion with him he makes a convincing argument for 'galaxy safety' and this not being 'sterilization' or 'genocide' but simply a check on the population. But the other side is easy to see too, deploying the genophage is playing god with this species, deciding for them what their population should be.  Why does the geneticist on your ship get to decide that? and how can he possibly know what the right population should be for this species? But then again, do you really want the galaxy completely over-run with these aggressive aliens? Tough choices.

This game is good because aside from being entertaining, there are points in this game that actually make you think.

2. Seeing women in positions of power

As explained in an Io9 article, by Kyle Munkittrick, sci-fi is historically able to push boundaries further than other media. A quote from that article:

"Science fiction is one of the best forms of social satire and critique. Want to sneak in some absolutely scandalous social mores, like, say, oh, I don't know, a black woman into a position of power in the 1960s? Put her on a starship command deck." 

And Mass Effect does that.  The 'tough soldier with a lot of health' character (you know the one, it shows up in every video game ever) is the second character you meet in ME1 and she is named Ashley. The all-powerful ruler of Omega who no one in their right mind would mess with is named Aria (also is voiced by Carrie-Ann Moss, who you might recognize from The Matrix and Memento).  The game is full of stereotype-destroying characters. It's not another sci-fi story where all the male characters have distinct personalities, but the one token woman character has the personality of 'woman'.  The women in Mass Effect show the same range of morality, toughness, power, and emotion that the men do. 

Omega only has one law: Don't fuck with Carrie-Ann Moss

However, Mass Effect is not a completely non-sexist game or anything.  There are plenty of females with comic-book proportions and there are even strip clubs.  The characters aren't all respectful of Commander Shepard when she is a woman (or man for that matter).  In a particularly brutal corner of the galaxy (Miranda calls it a 'piss hole'), you go to sign up for a mercenary mission and the jackass at the counter says 'sweetie, you're in the wrong place, strippers sign up over there.' (You can put him in his place for that remark if you choose to though).  It's not only sexism that runs rampant in the galaxy, people are speciesist to you too, one bar tender even tries to poison you because you are human. The thing that makes it a good game for women to play is because you see commander Shepard deal with people being rude to her, confront them, earn respect, do her job, and save the galaxy. 

1. Being a woman in a position of power. 

More important and more effective than just watching women in power, is actually 'being' a woman in power.  Modern video games like Mass Effect are highly immersive.  You move a character around, you see through her eyes, and you can even make her look like you.

In 2008, Galinsky et al. published a paper testing the effects of perspective taking.  That is, they had people pretend to be someone else, either by writing about their day as that person or by pretending to be that person in an interview.  They found that after pretending to be someone else, the participants of the study actually took on some of the stereotypes associated with the person they were imagining themselves to be.  For example, when they pretended to be a university professor, they rated themselves as smarter and actually performed better on an analytical task.  In contrast when they pretended to be a cheerleader, they rated themselves as more attractive but actually did worse on the analytical task. The most interesting thing here is that the effect was stronger when the participants were told to 'write about your day as if you were this cheerleader' than when they were told 'here is a cheerleader, write about her day.'

In short, pretending to be someone can influence how you feel about yourself and even how you act.
This is where Mass Effect can potentially have benefits even beyond watching a powerful woman role model on tv.  You actually pretend to be this woman: the commander of the ship, the leader of the team, the hero of the galaxy.  You answer as her during conversations. You make the tough decisions described above in Reason 3: Complex Morality. You stand up for yourself when you know you are right, but the alien council doesn't believe you. The fate of the galaxy rests on your shoulders.
If the perspective effect works in a video game setting, then pretending to be a strong woman for an hour a day, might actually make you a more confident person in real life.

I would love to see a study actually using this game to test the perspective taking effect in video games. Galinsky, are you listening? you should do this study:

Have women play Mass Effect (select some key conversations where respect is shown or tough decisions are made) and test whether it affects their self-reported confidence or intelligence.  An interesting control might be to have these women play Mass Effect as the male character and run through the exact same conversations.

Does taking the perspective of Commander Shepard boost confidence or ability? And if so is the effect increased when a woman plays as female Shepard compared to male Shepard? What if a man plays as female or male Shepard? The Cellular Scale wants to know!

© TheCellularScale

Galinsky AD, Wang CS, & Ku G (2008). Perspective-takers behave more stereotypically. Journal of personality and social psychology, 95 (2), 404-19 PMID: 18665710