Wednesday, January 30, 2013

Intuition or a sense of Smell?

I've long been fascinated by the idea that those feelings often attributed to 'intuition' or 'following your gut' might occur physiologically in the form of odor cues that we don't consciously register.

Intuition or Olfactuation? (source)
An example of this might me when you can just 'tell something is wrong' in a situation and decide to leave, and later found out that something bad happened later that evening. These sorts of stories are often used as evidence that people have psychic powers of some kind, and are equally often dismissed as just a coincidence.

But another possibility is that humans communicate through scents more than we realize. Maybe you could actually 'smell something is wrong' rather than supernaturally 'tell something is wrong' in the above hypothetical situation.

Researchers in the Netherlands tested whether the feelings of 'disgust' and 'fear' could be communicated through smell. They had guys watch scary parts of horror movies or disgusting graphic parts of MTV's Jackass while wearing 'sweat pads' in their armpits.

Who knew this would contribute to SCIENCE?

They then had female volunteers smell the sweat pads and measured their facial motions to see if the expressions they made were more like fear or disgust.

Importantly the protocol was double-blind, so neither the experimenters handing out the sweat pad vials, nor the participants had any idea what 'emotion' was sweated into those pads.

And they found what they thought they would find: the 'fear muscles' (Medial Frontalis) were most active for the women smelling the sweat of the horror-watching men, and the 'disgust muscles' (Levator Labii) were most active for the women smelling the sweat of the Jackass-watching men. In the authors words (stats taken out for readability):
"Moreover, fear chemosignals generated an expression of fear and not disgust, disgust chemosignals induced a facial configuration of disgust rather than fear, and neither fear, nor disgust, were evoked in the control condition" de Groot et al. (2012)
So at very very close range (like nose in armpit), it seems that emotional signals can be transmitted through scent.
The smell of fear (source)

A quick side note: the scent in this study was created by men and smelled by women. I wonder if this specific gender combination is necessary for the scent-based communication. You would think men smelling men and women smelling women would have the same effect, but they did not investigate other combinations.

If you learn anything from this, let it be to not go see a disgusting movie on a first date, you might end up repulsing each other with your 'disgust sweat' later.

© TheCellularScale
de Groot JH, Smeets MA, Kaldewaij A, Duijndam MJ, & Semin GR (2012). Chemosignals communicate human emotions. Psychological science, 23 (11), 1417-24 PMID: 23019141

Sunday, January 27, 2013

The Cellular Guide to Pipettes

What is a pipette?

Types of Pipettes (I took this picture)

There are lot of things that fall under the category of "pipette" and I found this a source of much confusion in my early graduate school days. Even after I knew by context what 'hand me the pipette' meant, I had a hell of a time trying to order the right type of pipette from scientific supply companies. 

So I am going to do you all a service, and give you a guide to pipette types: 

Labeled pipette types (I took this picture)
Basically, things that are long and skinny and can suck up certain amounts of liquid are called pipettes. 

Pipet-Aid: I think this is the brand name, but I didn't know what else to call it. It is battery powered and sucks liquid through an electrical vacuum. 

Serological pipet: This attaches to the pipet-aid and is calibrated for certain amounts of liquid. We use it for 10-25 mL volumes. 

Pipettor/pipette tip: This is the thing that I find most commonly referred to as a 'pipette.' They usually take smaller amounts (from microliters up to 5 milliliters) than the pipet-aid.

Pen: Do not try to use this as a pipette...or a pen. It's more 'cute' than it is 'able to write.'

Large transfer pipettes: These are plastic with squeeze-bulbs at the end.  They are not good for precise volumes of liquid like the others so far, but they are a quick easy way to transfer liquid from one place to another. We cut off the tip of the larger kind and use it to gently transfer brain slices into incubation chambers. 

Small transfer pipettes: I bought these on accident trying to replenish our supply of large transfer pipettes (#overlyhonestmethods). Now we use them to remove bubbles from the incubation chamber.

Pasteur pipette: These are glass and have detachable squeeze bulbs. I am not really sure what people use them for generally, but we have them in the lab left over from previous experiments. I use them to fill my pH meter with KCl and that's about it.  

Micropipette: This is a tiny pipette used for electrophysiology. The tip is so small that you can only see the opening under a relatively powerful microscope. The opening is smaller than the soma of a neuron, and I use these to patch onto brain cells. 

So there you have it: the ultimate guide to types of pipettes. I hope that one day this guide will save someone 20 minutes of online searching. 

If I missed some kind of pipette, please let me know! 

Tuesday, January 22, 2013

How to Build a Neuron: Step 5

And now, the final step in how to build your computational model of a neuron: Add Synaptic Channels. All the steps in this series can be found here.
Synapses connect neurons (source)
So you already have a neuron, and you've added intrinsic channels to it. The next thing you want to do is add synaptic channels so you can hook this neuron up to other cells.

The main synaptic channels you want to add are the excitatory channels: NMDA and AMPA and the inhibitory channel GABA. These channels don't have the same kind of activation and inactivation curves and the intrinsic channels do because they aren't activated by voltage, they are activated by a neurotransmitter.

AMPA and NMDA receptors are activated primarily by glutamate, and cause an influx of sodium and calcium ions. Since both sodium and calcium ions are positively charged, this depolarizes the cell membrane and brings it closer to firing an action potential.

AMPA receptors (source)
GABA receptors, on the other hand are primarily activated by GABA, and cause and influx of chloride ions into the cell. Because chloride ions are negatively charged, this hyperpolarizes the cell membrane and brings it further away from firing an action potential.

So if you want to have a realistic model of a neuron, you need to add an approximation of these channels. This is easier than adding intrinsic channels, because it is an on/off style (binary) rather than an analogue activation. So basically you just put in the parameters you want like how fast does the channel open and close, how much current does it allow through when activated, and where are they on the neuron.

Of course deciding these parameters is not always easy. A paper out this year in PLoS Computational Biology describes 4 different ways the NMDA receptor can be configured and analyzes the consequences during different stimulation patterns. 

Evans et al., (2012) Figure 3
The 4 NMDA configurations (based on the 4 different GluN2 subunits) vary in their sensitivity to a magnesium block, how fast they decay, and their maximal current. Above are their responses to the same stimulation patterns (an STDP protocol). Even though they were all receiving the same input pattern, they each show a very different response.

So when considering adding synaptic channels to your model neuron, take the time to find out what the configuration of the receptors should actually be in the type of neuron you are building.

© TheCellularScale

If you are good at following clues, you will realize that I am very, very familiar with this paper.

ResearchBlogging.orgEvans RC, Morera-Herreras T, Cui Y, Du K, Sheehan T, Kotaleski JH, Venance L, & Blackwell KT (2012). The effects of NMDA subunit composition on calcium influx and spike timing-dependent plasticity in striatal medium spiny neurons. PLoS computational biology, 8 (4) PMID: 22536151

Saturday, January 19, 2013

LMAYQ: Why do I like that?

Again it is time for me to answer some questions. As always, these are real true 'search terms' that have resulted in some one finding The Cellular Scale. While some questions (like 'how do you build a model of a neuron') are answered by this blog, the ones I answer is these LMAYQ posts are almost certainly not. All the questions and answers in this series can be found in the Let Me Answer Your Questions index.

Drawing by Grave Unicorn
1. "Why do I like ketamine so much?"

This is actually a pretty interesting question. Ketamine is a psychoactive drug known to cause hallucinations and feelings of dissociation, but it's not thought to be super-addictive in the same way that heroin or cocaine are thought to be. So why do you like it?

First let me get a 'safety warning' out of the way. Even though research is currently being conducted to investigate ketamine as an acute anti-depressant and to investigate its possible role in neurogenesis, it is not all considered a safe drug. It can seriously damage your urinary system for one thing, and probably damages your brain. Don't take it.

Ketamine (source)

Having said that, ketamine might give you a 'good feeling' because it is a partial agonist (meaning helps activate) the dopamine D2 receptor and the serotonin 5-HT2 receptor. In 2002, Kapur and Seeman published a paper showing that ketamine (and PCP) affects the dopamine and serotonin system by binding to these specific receptors. However dopamine is a confusing molecule and the idea that ketamine activates the D2 dopamine receptors does not necessarily mean 'pleasure.'

A classic test of 'wanting something' in rats is the self-administration paradigm, where rats can press a lever and get a dose of some drug or an electrical stimulation directly into the brain. A recent paper by De Luca and Badiani (2011) shows that rats will self administer ketamine when given the chance.
Interestingly, they found that the amount of self-administration was much higher when they took the rat out of its cage and put it somewhere new for the self-administration session. When the rat was allowed to self-administer ketamine in its home cage it just didn't give itself as much.

So your 'liking' of ketamine might have to do with where you are when you do it.
Kapur S, & Seeman P (2002). NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia. Molecular psychiatry, 7 (8), 837-44 PMID: 12232776

De Luca MT, & Badiani A (2011). Ketamine self-administration in the rat: evidence for a critical role of setting. Psychopharmacology, 214 (2), 549-56 PMID: 21069515

2. "What do neurons like?"

This question cracks me up because it reminds me of two personal anecdotes. First it reminds me of one of my professors who just can't stand when people say "the neurons behaved this way or that way." The idea being that behavior is a thing animals do, not a thing that neurons do. I basically agree that neurons don't behave per se, but I also don't really care if someone wants to 'be cute' by anthropomorphizing a cell.

Second, thinking about neurons 'liking' things or being happy reminds me of a yoga class when during the final relaxation segment, the teacher started saying things like 'You are happy. Your cells are happy, they are all smiling at each other.' It was hard for me to relax and let my cells smile at each other when all my willpower was being engaged preventing me from bursting into laughter.

Regardless, I will do my best to answer this question. I suppose, neurons 'like' glucose, which gives them energy. Other than that I don't think it's meaningful to talk about neurons liking things.

3. "Why do men like big women?" 

This is one of a long string of questions that resulted from me having the words 'small', 'men', 'like', 'big', and 'women' all in the title of a post. As you might imagine, this is far from the worst 'search term' that has dropped people onto that page.

And believe it or not, this question has a scientific answer.

A paper this year by Swami and Tovee (2012) investigates the influence of stress in men's judgement of women's bodies. They found that men who were stressed for just 15 minutes (by being forced to give a speech explaining how suitable they are for a job) found 'bigger' women more attractive than the men who were not stressed did.

Poor guy, if only he had a nice motherly type to cook him a pie. (source)
The 'explanation' could be (though this is speculation, of course) that bigger women represent more 'security.'
"The Environmental Security Hypothesis [15][16] suggests that, when socioeconomic or individual conditions are threatening or uncertain, individuals will prefer others with more mature physical characteristics, including a heavier body size, compared to their preferences in non-threatening conditions. This is because physical maturity is associated with the ability to handle threatening situations and because more mature physical features may communicate attributes such as strength, control, and independence during periods when such qualities should be most desired [15]." -Swami and Tovee (2012)
This paper is covered in more detail over at TryNerdy, and the paper is open access so you can read the source material if you want.
Swami V, & Tovée MJ (2012). The impact of psychological stress on men's judgements of female body size. PloS one, 7 (8) PMID: 22905153

© TheCellularScale

Tuesday, January 15, 2013

How big is the GIANT Squid Giant Axon?

With all the hubbub about the first ever video of an attacking giant squid in the wild about to unveiled, I started wondering about the giant axon of the giant squid... I mean it would be huge right?...

Giant Squid, Giant Axon? (source)
Squid are special creatures to neuroscientists. Specifically to neurophysiologists, who study the electrical activity of neurons.
Squid Axon location

Atlantic squid have this huge (1mm) amazing axon running down each side of their mantle which allowed for the first recordings of action potentials in the 1930s.

Here is a really nice 5 minute video showing how with (by today's standards) very crude techniques, the electrical signal could be recorded from these axons.

So the squid giant axon is neat, and modern neurophysiology would probably not exist with out it. But what about the GIANT squid giant axon? Wouldn't that be an electrophysiologist's dream?

If it scaled proportionally to say, mantle length, the 1foot long Atlantic squid with a 1mm diameter axon would become a 16 foot long GIANT squid with a 16mm giant axon.
Let's think about this for a minute, 16mm is about 5/8 of an inch. 

US coins for size reference
That is like the diameter of a dime! For those not familiar with US coins, it's like the size of a bead on a necklace... a big bead, like a nice-sized pearl. Basically HUGE considering that most axons in vertebrates are not even visible without a microscope.

However,before you all start running out to hunt the giant squid for its precious precious axon...the truth is that the giant squid does not have a super-giant dime-sized axon. The giant squid axon actually has a smaller diameter than the 'normal' squid axon.  Surprising right?
Do the giant squid just have more axons there, so they don't need one gigantic one? Or is this axon somehow magically myelinated (probably not)? Or does the giant squid just not need one?

First, let me explain that this information was pretty hard to come by and basically anecdotal. I watched a few dissections of giant squid. And while these were really amazing (look at the hooks on the colossal squid's tentacles!), they said very little about the giant axon or how it was modified in these larger animals.

hooks of the colossal squid tentacles, yikes! (source)
This information comes from a comment quoting JZ Young at a 1977 symposium describing his dissection of a 125cm (about 4 feet) long giant squid. I could not get access to this manuscript, so I have to trust the commenter with his quote:
“Everyone wants to know whether giant squids have giant giant fibres. We have no material of the central nervous system but some years ago I was able to dissect the stellate ganglion of an animal washed up at Scarborough in 1933 and sent to the British Museum. The mantle length was 125 cm. The nerves of the mantle muscles are arranged in this genus differently from any other I have seen. Those in the front part of the mantle arise from a relatively small stellate ganglion, in the usual way. The hinder part of the mantle, perhaps more than half of the whole, is suspended from a distinct median nerve, running with the fin nerve and giving off a series of branches to the mantle.
Each of the nerves arising from the ganglion contains one or two large fibres, ranging in diameter from about 80 micrometers in the more anterior ones to a maximum of 250 micrometers further back. The median nerve was further preserved but one fibre of about 250 micrometers could be seen. Two of the more posterior branches contained fibres of about 200 micrometers each. None of the nerves examined contained the exceptionally large fibres reported by Aldrich & Brown (1967). We may conclude that Architeuthis is not an especially fast-moving animal. This would agree with evidence that it is neutrally buoyant with a high concentration of ammonium ions in the mantle and arms (Denton, 1974).”
Young explains that the axon network is set up differently in the giant squid (Architeuthis). He reasons that because the axon is not especially large, it could only conduct so fast, and therefore the fast escape reflex which it causes in the normal squid is just not that fast in the giant squid. This sort of makes sense, in that the giant squid might not benefit from escape as much as the normal squid. The giant squid might be better served by having razor sharp teeth on its suckers or terrifying pain causing-hooks so it could fight away a predator. 

The biggest axon award goes to the Humboldt Squid which has an axon the 'size of spaghetti.'

And while the first ever video of a giant squid just came out, the first ever photographs from the wild were published in 2005.

© TheCellularScale Kubodera T, & Mori K (2005). First-ever observations of a live giant squid in the wild. Proceedings. Biological sciences / The Royal Society, 272 (1581), 2583-6 PMID: 16321779

JZ Young, 1977 The Biology of Cephalopods Symposia of the Zoological Society of London #38

Friday, January 11, 2013

On Selling and Over-Selling Science

Science!!! (source)
Science communication is a persistent topic of ... well communication. Who is responsible for communicating science? How can science be best communicated to the public? What can we to do stop sensationalist and misleading articles from controlling what findings are generally accepted in the public sphere?

All these questions rise up in science blogs and on twitter and then fade back into the background. Then something happens and a flurry of posts about communicating science float to the surface again.

I have decided to join this party, and have written a Guest Editorial at the Biological Bulletin.

It's called "On Selling and Over-Selling Science" and is about trying to find that perfect balance between communicating a scientific finding accurately and accessibly.

I'd love to hear new opinions on this. So feel free to follow the link and leave a comment about it here. 

© TheCellularScale

I was not able to use my 'blogging name' like Neuroskeptic was, so here is the article and my identity along with it:
Evans RC (2012). Guest editorial on selling and over-selling science. The Biological bulletin, 223 (3), 257-8 PMID: 23264470

Monday, January 7, 2013

Does a high fat diet lead to a less 'rewarding' life?

Some interesting research out of the University of Pennsylvania suggests that a high fat diet can disrupt dopamine signalling.

This high-fat fed rat sure looks happy to me (source)
As I briefly discussed during my SfN Neuroblogging binge, a high fat diet can alter dopamine levels in the brain. To expand on this, we'll look at new research on how exactly this might happen and which specific areas of the brain are affected.  

Vucetic et. al. (2012) tested the levels of dopamine-related gene expression (via mRNA) in the hypothalamus and the ventral tegmental area (VTA). The hypothalamus is important because it controls your levels of hunger as well as many other things. The VTA is important because it is the main source of dopamine to the ventral striatum (AKA the Nucleus Accumbens). The VTA-nucleus accumbens pathway is generally thought to signify 'reward' when it is activated. Sex, Drugs, Music, and lots of other 'pleasurable' activities all activate this pathway. So alterations in the dopamine levels here might change how 'rewarded' a person (or mouse in this case) feels in response to pleasurable stimuli.

So Vucetic et al., (2012) found that in the VTA, the levels of tyrosine hydroxylase ("TH", an enzyme indicative of how much dopamine can be made) and dopamine active transporter ("DAT", which gets rid of excess dopamine at the synapse) are both reduced in the mice eating the high fat diet.

Vucetic et al. (2012) Figure 1
By contrast, in the hypothalamus, TH and DAT are both increased due to the high fat diet.

So what does this mean? The authors point out that increased dopamine in the hypothalamus actually promotes eating. Consistent with this idea, the authors show that mice eating the high fat diet actually ate more frequently and ate more total food. Secondly, when there is less dopamine in the VTA, it is likely that a rewarding stimuli will seem less rewarding. 

In the author's words:
"Collectively, these behaviors have the potential to promote obesity in two distinct ways: (i) through an increase in food intake and (ii) by increasing the drive for palatable food, as the animal with a blunted response to palatable foods may seek and/or consume these food relatively more than a normal animal in order to reach the same rewarding response. "
So basically the mice aren't obese because the food they are eating is high fat, they are obese because they are eating MORE food. But of course, they are eating more food because the high fat diet makes them 'want' to eat more food, so the high fat diet is indirectly causing the weight gain.

It is truly a vicious cycle.

 *Note: They also look at epigenetic effects on the TH and DAT promoter DNA. If you are interested in that aspect of the study, comment and I can do a follow-up post explaining it, or you can just read the study for yourself, following the link below. 

© TheCellularScale
Vucetic Z, Carlin JL, Totoki K, & Reyes TM (2012). Epigenetic dysregulation of the dopamine system in diet-induced obesity. Journal of neurochemistry, 120 (6), 891-8 PMID: 22220805

Friday, January 4, 2013

Cellular Recap of 2012 #2: favorites

As promised, here are my favorite posts from each month.

January: The Human Neuron" not so special after all?

Butti C, Santos M, Uppal N, & Hof PR (2011). Von Economo neurons: Clinical and evolutionary perspectives. Cortex; a journal devoted to the study of the nervous system and behavior PMID: 22130090

February: If you give a mouse a placebo...

Wise RA, Wang B, & You ZB (2008). Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release. PloS one, 3 (8) PMID: 18682722 

March: Plant neurons: Sensation and Action in the Venus Flytrap

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

April: Real or Not Real? Neurotorture

Kindt M, Soeter M, & Vervliet B (2009). Beyond extinction: erasing human fear responses and preventing the return of fear. Nature neuroscience, 12 (3), 256-8 PMID: 19219038

May: Dendrites of Direction

Kim IJ, Zhang Y, Yamagata M, Meister M, & Sanes JR (2008). Molecular identification of a retinal cell type that responds to upward motion. Nature, 452 (7186), 478-82 PMID: 18368118

Kay JN, De la Huerta I, Kim IJ, Zhang Y, Yamagata M, Chu MW, Meister M, & Sanes JR (2011). Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (21), 7753-62 PMID: 21613488

June: What do Mirror Neurons look like?

Kraskov A, Dancause N, Quallo MM, Shepherd S, & Lemon RN (2009). Corticospinal neurons in macaque ventral premotor cortex with mirror properties: a potential mechanism for action suppression? Neuron, 64 (6), 922-30 PMID: 20064397

Casile A, Caggiano V, & Ferrari PF (2011). The mirror neuron system: a fresh view. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 17 (5), 524-38 PMID: 21467305 

July: The Shape of a Memory

Blackiston DJ, Silva Casey E, & Weiss MR (2008). Retention of memory through metamorphosis: can a moth remember what it learned as a caterpillar? PloS one, 3 (3) PMID: 18320055

August: How to Build a Neuron: Step 1

Marx M, Günter RH, Hucko W, Radnikow G, & Feldmeyer D (2012). Improved biocytin labeling and neuronal 3D reconstruction. Nature protocols, 7 (2), 394-407 PMID: 22301777 

September: Taste cells in weird parts of your body

Finger TE, & Kinnamon SC (2011). Taste isn't just for taste buds anymore. F1000 biology reports, 3 PMID: 21941599
 October: Can you turn a rat gay? 

Triana-Del Rio R, Montero-Domínguez F, Cibrian-Llanderal T, Tecamachaltzi-Silvaran MB, Garcia LI, Manzo J, Hernandez ME, & Coria-Avila GA (2011). Same-sex cohabitation under the effects of quinpirole induces a conditioned socio-sexual partner preference in males, but not in female rats. Pharmacology, biochemistry, and behavior, 99 (4), 604-13 PMID: 21704064

 November: Growing 3D cells 

Labour MN, Banc A, Tourrette A, Cunin F, Verdier JM, Devoisselle JM, Marcilhac A, & Belamie E (2012). Thick collagen-based 3D matrices including growth factors to induce neurite outgrowth. Acta biomaterialia, 8 (9), 3302-12 PMID: 22617741

December: Cortical spine growth and learning how to eat pasta

Fu M, Yu X, Lu J, & Zuo Y (2012). Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature, 483 (7387), 92-5 PMID: 22343892

© TheCellularScale

Wednesday, January 2, 2013

A cellular 2012

It's been an exciting first year of blogging here at The Cellular Scale.
Glowing Neuron
Let's take a look back at the Cellular year, shall we?

I am going to do this two ways: Today I'll post the first sentence of the first post of each month from this blog as is a blogging tradition. Next post, I'll list my personal favorite posts from each month.

January: "Hello and welcome to The Cellular Scale."

February: "Food smells better when you're hungry, right?"

March: "Another adventure out side the "cellular neuroscience" walls for The Cellular Scale."

April: "I love reading other blog posts about ridiculous scientific (and unscientific) claims."

May: "How do you build a virtual environment for a worm?"

June: "Andrew Huxley is one of the founders of both modern electrophysiology and  computational neuroscience, and is consequently a personal hero of mine."

July: "...toward preventing PTSD symptoms."

August: "Zebra finches are a popular model for language learning because unlike most research animals which may have instinctual vocalizations, zebra finches (the male ones at least) learn their signature song from experience."

September: "I have always believed that scientific research is another domain where a form of optimism is essential to success: I have yet to meet a successful scientist who lacks the ability to exaggerate the importance of what he or she is doing, and I believe that someone who lacks a delusional sense of significance will wilt in the face of repeated experiences of multiple small failures and rare successes, the fate of most researchers"     -Daniel Kahneman

October: "It's about to get really neuro-heavy here at The Cellular Scale because of the impending Society for Neuroscience annual conference."

November: "Time to get back to Answering Your Questions."

December: "Seriously."

© TheCellularScale