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Aug20

Flashback: Noise in the brain?

In: blogarchives • Tags: free will, noise, spontaneity, variability

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from May 8, 2009:

I was recently alerted to a group of theoretical publications which deal with the issue of apparent ‘noise’ in neuronal populations. The Nature Reviews Neuroscience article “Neural correlations, population coding and computation” by Bruno B. Averbeck, Peter E. Latham &  Alexandre Pouget covers this area quite well.
Basically, the authors claim that the variability one can see when recording from the brain when the same stimulus is presented repeatedly is noise and must be detrimental for the tranmission of information and hence a problem the brain must solve:

Part of the difficulty in understanding population coding is that neurons are noisy: the same pattern of activity never occurs twice, even when the same stimulus is presented. Because of this noise, population coding is necessarily probabilistic. If one is given a single noisy population response, it is impossible to know exactly what stimulus occurred. Instead, the brain must compute some estimate of the stimulus (its best guess, for example), or perhaps a probability distribution over stimuli.

It needs to be noted that the authors do not refer to sensory neurons, which code sensory information with great precision. Instead, they look at neurons deep in the mammalian brain, many synapses away from the primary sensory afferents. What I don’t understand from their article is why this should be considered ‘noise’. Obviously, if high fidelity between the site of sensory input and the site of recording were required, there would be a single axon going there, and not via many syapses. Synapses are time consuming and energetically expensive. During development, unused synapses are being pruned throughout the brain. Thus, the variability must reflect some computation which takes place in the synapses from the site of sensory input to the site of recording. Let me illustrate this with a picture:

neuralnoise.png

Of course, if one records from neuron NR and stimulates sensory neuron NS, as in A, there is a lot of processing going on in the synapses along N1-4. This is happening even without any external input into the single conveyor belt of information. Of course, there never is such a conveyor belt, that idea is already misleading. After the very first synapse (from wherever you start), there are always inputs from other sites, feed-forward and feedback connections, etc. But even in this simplest model of information transmission, every synapse is a computational component and not just a link between neurons adding variability to the sensory signal for no reason. These synapses would not be there if this processing was not some important brain function. This is illustrated in B: if simple and reliable information transmission from NS to NR were important, there would only be one single axon from NS to NR, without any additional processing.

I would really like to hear good arguments as to why the recorded variability should be ‘noise’ and a problem for information coding, rather than a reflection of the brain doing what it’s supposed to do: finding out what the best action is under the current circumstances.


Averbeck, B., Latham, P., & Pouget, A. (2006). Neural correlations, population coding and computation Nature Reviews Neuroscience, 7 (5), 358-366 DOI: 10.1038/nrn1888

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Posted on August 20, 2013 at 16:55 Comments Off on Flashback: Noise in the brain?
Aug19

Science, red in tooth and claw

In: blogarchives • Tags: open access, sabotage, stress, tenure

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from September 30, 2010:

I’ve been contemplating the current competitive state of science here before. The gist of it was that science may be suffering from too much competition, leading to an increasing incidence of misconduct, such as falsifying or omitting inconvenient data. In this week’s Nature appeared a news-report which tells me that apparently the pressure cooker which is our scientific community apparently has been set to a notch hotter recently.

The article is about the sentencing of a postdoc who has been sabotaging the work of a graduate student in his own lab for several months. The postdoc has admitted – after being caught on secret camera – to have poured ethanol in the culture medium for the cell culture of the graduate student as well as contaminating Western blots of the student.

In my previous posts I speculated that fraud and other, related misconduct may be on the rise as more and more trained scientists are faced with less and less positions for which they compete. I did not expect this form of misconduct and neither did anybody else: sabotage is not officially part of the canon of research misconduct and thus no federal agency was able to prosecute the perpetrator.

As all of the cases which make it into the media, this is another anecdote and the plural of anecdote is not data. Nobody knows if the frequency of misconduct is rising or if the publicized cases simply come with the growth of the business. Nevertheless, this form of direct sabotage of researchers by researchers seems to be a novel quality of competition-induced research misconduct.

What will we see next?

Hot on the heels of the stunning sabotage case comes a seemingly unrelated report in The Scientist that US libraries are forced to cut scientific journal subscriptions by the thousands due to budget cuts:

New Mexico State University (NMSU) library announced the cancellation of over 700 journal and database subscriptions, the result of a perfect storm of rising journal prices and a slashed materials budget. […] A 2009 global survey of 835 libraries in 61 countries found that nearly one-third of academic libraries saw their budgets reduced by 10 percent or more that year. And journal subscriptions are taking the brunt of that loss: The University of California at San Francisco (UCSF) cancelled 118 print and 115 online subscriptions for 2010, as well as several databases (including Faculty of 1000 Medicine, publisher of The Scientist). Last spring, the University of Washington announced cuts of 1,600 print and electronic journals, databases, and microforms. The University of Virginia library sliced 1,169 journals, the University of Arizona downsized by 650 print and electronic titles, and Georgia State University cut 441 and is now considering the fate of another 1,092. The list goes on and on.

While on the surface these two reports seem unrelated, they in fact demonstrate the coming scientific system: too many highly trained scientists competing for a position in a system that is so cash-strapped that even access to the literature is threatened. Access to the literature is the most basic prerequisite for doing science. One of the quotes in the article demonstrates that: “I need the EBSCO databases like I need air or water!”

Just as now access to drinking water is a human right, access to the literature should be a scientific right.

German psychologist Bally in the 1940s and later ethologist Hasenstein in the 1970s coined the term “eased-up field” (entspanntes Feld) for a situation where all the basic needs are satisfied. They found that exploratory or playful behavior decreased in virtually all subjects tested, be it human or animal, whenever the animals were not in an eased-up field. Currently, science almost on a world-wide scale is heading towards a situation in which each scientist’s livelihood is threatened as well as one of the basic prerequisites for doing science, access to the literature. Neither of these trends alone bodes well for the quality of future science, but both trends together serve to basically block the emergence of the creative genius required for major scientific breakthroughs.

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Posted on August 19, 2013 at 21:21 1 Comment
Aug18

Flashback: Nothing new in science?

In: blogarchives • Tags: behavior, decision-making, Drosophila, neurogenetics, phototaxis

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from February 9, 2011:

 

In this week’s journal club, we talked about an old paper from 1918! “The reactions to light and to gravity in Drosophila and its mutants” by Robert McEwen, in the Journal of Experimental Zoology.

As the title says, the author studied how the fruit fly Drosophila responds to light and gravity. He tested this in walking flies and compared flies both with intact wings and clipped wings, wing mutations, clipped antennae, glued wings or clipped middle legs. He discovered that flies without wings or with mutated wing shape, show less movement towards light (i.e., less phototaxis). This finding was later confirmed by one of the founders of modern neurogenetics, Seymour Benzer (1967) and we also find this in our experiments. We have now set out to find out which neuronal mechanisms are involved in this drastic change in behavior.

In order to get the flies to show phototaxis, McEwen developed a machine to gently tap the tube in which the flies were placed, to get them to walk. He described the necessity for flies to be active in order to show a consistent orientation towards a light source: without walking behavior being either initiated spontaneously or by the tapping machine, flies would not walk towards the light themselves. If the flies were at rest, light was not an orienting stimulus for them. This key insight was formulated by McEwen at the very end of the paper:

Lastly, it may be well to emphasize the peculiar relation which exists in Drosophila between general activity and phototropism. This phenomenon has been clearly recognized by Carpenter and in general I agree with this author’s conclusions. The fact seems to be that this insect is not phototropic unless it is in a certain physiological state brought on by, or at least accompanied by, activity. When the fly reaches a certain degree of activity, induced by various means, it suddenly becomes phototropic. When it quiets down, however, it may still crawl about but ceases to be phototropic. Thus, when an insect has been exposed to constant illumination for some time, it no longer orients to light but wanders aimlessly up and down the tube. Eventually such an animal may even come to rest with its head away from the source of light.

The technique described mimics what other colleagues have later developed in other fly paradigms based on vision and walking, such as the “fly-stampede” paradigm. But the insight reaches much further than that. More recent research has shown that the state of the animal has minute control over how the environment is processed. For instance, leeches respond with various behaviors to local mechanosensory stimulation (i.e., touch). However, when they feed, the biogenic amine serotonin is released and prevents the mechanosensory neurons from transmitting the stimuli – the animal becomes unresponsive when it feeds (Gaudry & Kristan, 2009). Another study showed that motion-sensitive neurons in the optic lobes of the fly brain increase their gain when the fly is flying, as opposed to when it is not flying (Maimon et al., 2010). Analogous results were obtained when walking vs. sitting flies were compared (Chiappe et al. 2010). In another, also very sophisticated study, Haag et al. (2010) showed how an identified motor neuron responds more strongly to visual input when the animal is flying than when it is at rest. Finally, Tang and Juusola (2010) report evidence that the direction in which a fly attempts to turn changes the way in which the optic lobes process the visual information on the side towards the fly attempts to turn, compared to the contralateral side.

All these groups have, largely independently of each other, discovered the biological mechanisms for something that already McEwen (and Carpenter, cited there) had understood: animals don’t just respond to stimuli in always the same, stereotypical way: all animals have many different ways to treat and evaluate the incoming sensory stream, depending on what they are doing at the moment. The decisive factor for understanding animal behavior is not the environment, or the sensory organs, it is the animal itself. Apparently, this profound insight was known long ago and we’re just rediscovering it now, in various places, all over the world.

Something was new in all the recent studies, though: they all provide first mechanistic insight into how brains balance internal and external processing. All these studies show that there seems to be a smooth gradient between decision-making and attention-like processing, even in invertebrates: Gaudry and Kristan call it decision-making, when their leeches ‘decide’ to ignore stimuli while they feed, even though the incoming sensory stimuli are blocked already at the very first synapse. Chiappe et al., on the other hand, relate their phenomenon to attention and Haag et al. also mention attention in their paper, with their effects being observed many synapses downstream of the sensory neurons – the word ‘decision’ does not occur in either of the two papers. It appears as if future neurophysiological research is bound to show that the distinction between attention-like mechanisms and decision-making, which seems so intuitive and clear-cut, may dissolve when we start to unravel how brains actually do it. Now when will we come accross the ancient text that already pre-empts that insight? nuetral.png

References:


McEwen, R. (1918). The reactions to light and to gravity in Drosophila and its mutants Journal of Experimental Zoology, 25 (1), 49-106 DOI: 10.1002/jez.1400250103
Zhu, Y., & Frye, M. (2009). Neurogenetics and the “fly-stampede”: dissecting neural circuits involved in visual behaviors Fly, 3 (3), 209-211 DOI: 10.4161/fly.3.3.9139
Gaudry, Q., & Kristan, W. (2009). Behavioral choice by presynaptic inhibition of tactile sensory terminals Nature Neuroscience, 12 (11), 1450-1457 DOI: 10.1038/nn.2400
Maimon, G., Straw, A., & Dickinson, M. (2010). Active flight increases the gain of visual motion processing in Drosophila Nature Neuroscience, 13 (3), 393-399 DOI: 10.1038/nn.2492
Chiappe, M., Seelig, J., Reiser, M., & Jayaraman, V. (2010). Walking Modulates Speed Sensitivity in Drosophila Motion Vision Current Biology, 20 (16), 1470-1475 DOI: 10.1016/j.cub.2010.06.072
Haag, J., Wertz, A., & Borst, A. (2010). Central gating of fly optomotor response Proceedings of the National Academy of Sciences, 107 (46), 20104-20109 DOI: 10.1073/pnas.1009381107
Tang, S., & Juusola, M. (2010). Intrinsic Activity in the Fly Brain Gates Visual Information during Behavioral Choices PLoS ONE, 5 (12) DOI: 10.1371/journal.pone.0014455

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Posted on August 18, 2013 at 10:28 1 Comment
Aug16

Scientific discoveries are like orgasms: you can’t have any bad ones

In: blogarchives • Tags: dunning-kruger, incompetence, publishing

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from June 24, 2010:

What is it with non-scientists trying to go and save science from the scientists? First, there’s an English major at Scholarly Kitchen trying to tell us we should stick with a 400 year-old publishing system despite more modern systems being widely and readily available. Then the same blog sports a post wondering why their 400 year-old system they just touted doesn’t seem to operate as they imagine. So first these guys write a post to make sure every scientist who reads it understands that they have no clue and then they wonder why their clueless and hence baseless predictions don’t materialize? WTF? peeved.png I have an answer for The Scholarly Kitchen: because what you imagine how science works has nothing to do with reality!

Then there is a completely weird article in The Chronicle of Higher Education on how we need to get rid of all ‘low-quality’ science. This piece, probably not unexpected by now, was written by English, management, mechanical engineering and geography professors. The lone medical researcher in the group does have a fair amount of PubMed articles, but none of them are in one of the supposedly high-quality journals mentioned in the article, so he basically just called himself ‘low-quality’ and thus should be struck from the public record, grin.png Moreover, the articles where he was single author or one of two authors are all on clinical practice and testing, raising the tentative suspicion that medical practice is really his strong area of expertise, rather than science. Which means that, again, none of these guys is actually a scientist, i.e., working in physics, chemistry, biology and regularly publishing scientific, experimental papers, which makes up the bulk of the scientific literature. If they were, they would know that there isn’t such a thing as a ‘low-quality’ scientific discovery. Scientific discoveries are like orgasms: you can’t have any bad ones. Now, I agree that there are badly conducted experiments, missing control procedures and outright fraud. None of these examples are eliminated by reducing scientific output, obviously. The authors make sure that this is not what they mean, as they refer to ‘low-quality’ science as journals or papers that aren’t cited. Obviously, hi-profile fraud cases are cited a lot. One reason for low citation counts is that very few scientists understand the topic and/or are interested in it. Clearly, this can change in a heartbeat and what was boring one day can be all the rage tomorrow. Only someone not steeped in scientific research would not be aware of that. Not surprisingly, this article has received a thorough smackdown in the comment section over there and in the blogosphere.

And then finally, to cap it all off, this completely inane post, riddled with factual errors, ludicrous assumptions and outright slander. The author characterizes himself as the person who trademarked the term “Science 2.0”. Moreover, in the comments, he gives it away: “I’m not a researcher” (as if that wasn’t already blatantly obvious from the post). I wonder why he’s even touching his keyboard such that it generates these nonsensical sentences? This post contains about as much valuable and accurate information as if a monkey had sat on the keyboard. By his own admission, he has about as much competence in this topic as a monkey’s rear end. This guy could probably just go and give it a shot trying out for the LA Lakers – at least he couldn’t be any less qualified than for his chosen topic.

I’m a biologist. Do I go to engineers and tell them how to build bridges? Do I try to play in the NBA? Do I tell BP to just put a lid on it? Sheesh, why are so many people trying to outcompete each other to exemplify the Dunning-Kruger effect these days? These guys are even more pathetic than Rupert Pupkin in The King of Comedy. What’s with this current slate of ignorant imbeciles trying to grandstand as if they had any relevant competence whatsoever and address an international group of hundreds of thousands of professionals with the actual expertise and experience? Where do these guys get the idea they have anything meaningful and worthwhile to contribute? What’s gotten into them?  A different collusion of delusion? elated.png

claimtoken-520f68e90ad03

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Posted on August 16, 2013 at 09:15 Comments Off on Scientific discoveries are like orgasms: you can’t have any bad ones
Aug15

Flashback: Creationists, this is the evidence you have to beat!

In: blogarchives • Tags: archeology, creationism, evolution, genetics, language

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from April 19, 2011:

 

The last decades of research on human evolution have provided an astounding body of converging evidence for an African origin of the human lineage just under about 200k years ago, with a subsequent migration across the globe starting around 60k years ago until all the main regions of this planet were inhabited by humans at around 15k years ago. Compare this scenario to the creationist story, where humans were shaped by a magic man out of clay about 6k years ago, which means it happened just after the Sumerians have invented glue.What is the converging evidence telling the “Out of Africa” story?It all started with fossils and artifacts. Archeology, with its own dating techniques and collection methods, suggested a route that looks something like this:


(Image source)

Later, genetic evidence came along. Geneticists, with their own dating techniques and experimental methods suggested migration routes that looked something like this:


(Image source)

After the genetic evidence, came evidence from a bacterium associated with humans: Helicobacter pylori. It lives in our guts and can cause stomach ulcers. It’s been associated with our digestive tract for many thousands of years. Looking at the different strains of these bacteria, microbiologists, using their own dating techniques and experimental protocols, deduced that this bacterium in our guts must have traveled roughly along these routes:

hpylori_evol_small.jpg
(Image source)

Most recently, linguists came along and studied the phonemes that make up 504 of the different human languages around the globe. These linguists adopted the analysis tools from the geneticists to their own dating techniques and sampling methods and came up with a map that suggested the following main routes along which the human languages seem to have developed:


(Image source)

Clearly, getting the dates correct using phonemes will prove a lot harder than the previously used dating techniques. Nevertheless, these are four independent lines of evidence, collected over many decades by scientists with vastly different backgrounds and training. Yet, the results agree to an astonishing extent.

However, this doesn’t mean it’s ‘true’ or ‘scientifically proven’. It only means that this is the best humans can currently possibly do and anything new that comes along must not only explain the current congruence of disparate data, but also explain more data, than the current ‘Out of Africa’ theory can explain. A few self-contradictory passages in an ancient text do not even begin to come close to being a contender.

Given this sort of evidence, it becomes rather obvious that creationists are either uninformed or unpersuadable. For the former, information like the one in this post should be more than sufficient to falsify the creationist dogma. For the latter, ridicule and derision is the best response.

This post was inspired by Lapidarium Notes.


Pertinent peer-reviewed literature:

  • Green, R., Krause, J., Ptak, S., Briggs, A., Ronan, M., Simons, J., Du, L., Egholm, M., Rothberg, J., Paunovic, M., & Pääbo, S. (2006). Analysis of one million base pairs of Neanderthal DNA Nature, 444 (7117), 330-336 DOI: 10.1038/nature05336
  • Linz, B., Balloux, F., Moodley, Y., Manica, A., Liu, H., Roumagnac, P., Falush, D., Stamer, C., Prugnolle, F., van der Merwe, S., Yamaoka, Y., Graham, D., Perez-Trallero, E., Wadstrom, T., Suerbaum, S., & Achtman, M. (2007). An African origin for the intimate association between humans and Helicobacter pylori Nature, 445 (7130), 915-918 DOI: 10.1038/nature05562
  • Atkinson, Q. (2011). Phonemic Diversity Supports a Serial Founder Effect Model of Language Expansion from Africa Science, 332 (6027), 346-349 DOI: 10.1126/science.1199295

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Posted on August 15, 2013 at 18:16 Comments Off on Flashback: Creationists, this is the evidence you have to beat!
Aug13

Neither gold, nor green, nor hybrid are sustainable open access models

In: blogarchives • Tags: journal rank, open access, publishing

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from December 28, 2012:

If you trust empirical evidence, science is currently heading for a cliff that makes dropping off the fiscal cliff look like a small step in comparison. As we detail in our review article currently under revision, retractions of scientific articles are increasing at an exponential rate, with the majority of retractions being caused by misconduct and fraud (but also the error-rate is increasing). The evidence suggests that journal rank (the hierarchy among the 31,000 scientific journals) contributes a pernicious incentive: because funds are tight and science is increasingly under pressure to justify its expenditure, people are rewarded for publishing in high-ranking journals. However, there is no empirical evidence that science published in these journals is any different from scientific discoveries published in other journals. If anything, high-ranking journals publish a much larger fraction of the fraudulent work than lower ranking journals and also a larger fraction of the unintentionally erroneous work. In other words, journal rank is like homeopathy, astrology or dowsing: one may have the subjective impression that there is something to it, but any such effects disappear under scientific scrutiny.

As journal rank has only been used as an instructor for the hire-and-fire policy and institutions world-wide for a few decades, the data also project some potentially catastrophic consequences of journal rank: science has been hiring those candidates who are especially good at marketing their science to top journals, but maybe not equally good at the science itself. Conversely, excellent scientists were fired who did not reach institutional requirements for marketing their research. If this is really what has been taking place, it has now been going on just long enough by now to replace an entire generation of scientists with researchers who are particularly good at marketing, providing one potential explanation of why the fraud and retraction rate is exploding just at this particular point in time. However, until a few years ago, this has been a trend that has only been observed by a few bibliometricians.

At the same time, a much more obvious trend has been receiving a lot of attention: the rising costs of acess to the scholarly literature. To counter this trend, three different publishing models have emerged, which only address the access problem, but not the parallel, and potentially underlying problem of journal rank. These models aim to provide unrestricted, open access to publicly funded research results either by charging the authors once for each article (gold), or by mandating them to place a copy not of the final PDF, but of the version approved by the referees (i.e., the version before the publishers format it) in institional repositories (green), or by providing an option for authors to make heir article accessible in a subscription journal by an additional article fee, i.e., if the authors pay the fee, their article becomes openly accessible, if not, it stays behind a paywall (hybrid). Importantly, the three models which are currently aimed at publishing reform are not sustainable in the long term:

  1. Gold Open Access publishing without abolishment of journal rank (or heavy regulation) will lead to a luxury segment in the market, as evidenced not only of suggested author processing charges nearing 40,000€ (US$~50,000) for the highest-ranking journals, but also by the correlation of existing author processing charges with journal rank. Such a luxury segment would entail that only the most affluent institutions or author would be able to afford publishing their work in high-ranking journals, anathema to the meritocracy science ought to be. Hence, universal, unregulated Gold Open Access is one of the few situations I can imagine that would potentially be even worse than the status quo.
  2. Green Open Access publishing entails twice the work on the part of the authors and needs to be mandated and enforced to be effective, thus necessitating an additional layer of bureaucracy, on top of the already unsustainable status quo.
  3. Hybrid Open Access publishing inflates pricing and allows publishers to not only double-dip into the public purse, but to triple-dip. Thus, Hybrid Open Access publishing is probably the most expensive version overall for the public purse.

Thus, what we have now is a status quo that is a potential threat to the entire scientific endeavor both from an access perspective and from a content perspective, and the three models being pushed as potential solutions are not sustainable, either. The need for drastic reform has never been more pressing.

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Posted on August 13, 2013 at 19:49 2 Comments
Aug12

Flashback: The neurobiology of operant conditioning

In: blogarchives • Tags: Drosophila, FoxP, neurogenetics, operant, PKC, rutabaga, self-learning

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from April 28, 2011:

It turns out, operant conditioning is very different from other forms of learning, all the way from the genes up. When I started my research on operant conditioning in 1995, I did so with the opposite hypothesis, namely that the underlying mechanism of all learning processes was always synaptic plasticity with the well-known molecular pathway: Ca++, cAMP, PKA, CamK, CREB and so on. After all, wasn’t that pathway conserved all the way from flies, snails and mice to humans? By the time I finished by PhD in 2000, Eric Kandel had received the Nobel prize for exactly these learning mechanisms – he wouldn’t have gotten the prize if the pathways had not been so conserved. In principle, changing the weight of the synapses is all you need to do to store whatever information you want. There is no a priori need to have several different mechanisms by which neural networks are modified.

A few years ago, I started getting data from fruit flies ( Drosophila) that were exactly the opposite of what my initial hypotheis was: the genes required for standard synaptic plasticity (such as the rutabaga adenylyl cyclase) were not required in our form of operant conditioning. In contrast, a gene which had previously been shown not to be involved in classical conditioning, protein kinase C (PKC) turned out to be crucial for operant conditioning. What made the whole story even more intriguing was that the same evidence started to show up in the lab where I did my postdoc, using the marine snail Aplysia as a model system: PKC was required, but the rut-cyclase was not.

Why had nobody discovered this dichotomy between the learning mechanisms before us? It turned out that the crucial experimental advance was to prevent the animals from learning about anything else besides their behavior. As soon as we let the animals learn about any external cues in addition to their behavior, the results go back to the expected canonical pathways being required and PKC not. Obviously, nobody had been able to completely isolate operant conditioning to the extent that was required. Because all our experiments were operant in nature, but only differed in whether or not the animals were able to learn about environmental cues or not, we called the PKC-dependent learning mechanism operant self-learning and the other, well-described form, operant world-learning.

How far is this new form of plasticity (in Aplysia it is a form of ‘intrinsic plasticity’ modifying the entire neuron and not just the synapse; in Drosophila we don’t know) conserved? We are currently in the process of writing up our experiments on the ‘language gene’ FoxP2. Drosophila has an orthologue of this gene and if we mutate it (or knock it down with RNAi), we find that it is required for operant self-learning, but not for operant world-learning, paralleling the results we had for PKC. This means we now have a new learning mechanism at hand that is clearly distinct from the well-known synaptic plasticity pathway, but is equally conserved among invertebrates and vertebrates. These results suggest an ancient evolutionary origin for operant self-learning, possibly at the root of the bilaterian branch, and a complementary role to world-learning.

I have summarized these results in an invited review on occasion of the 2010 conference of SQAB in the journal “Behavioural Processes”. Unfortunately, there are a few mistakes in the copy available from the publisher. Some spaces are missing between words and the references Brembs 2009a and Brembs 2009b are mixed up. I’ve notified the publisher, but they said it was too late to fix. I’ve now fixed the HTML version of my local copy, but I can’t fix my PDF copy as they use a font that is not freely avaliable. So if anybody knows how I can fix my own PDF copy, please let me know!


Brembs, B. (2011). Spontaneous decisions and operant conditioning in fruit flies Behavioural Processes DOI: 10.1016/j.beproc.2011.02.005

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Posted on August 12, 2013 at 21:09 Comments Off on Flashback: The neurobiology of operant conditioning
Aug11

SummerScienceVideo: science is real

In: blogarchives • Tags: fun, science, video

As part of my scheduled re-posts during the summer break, I’ll also post some of the science videos from the archives. I originally posted this one on Agust 31, 2011:

A nice song with a really cool little video:
They Might Be Giants - Science is Real (official TMBG video)
They Might Be Giants - Science is Real (official TMBG video)

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Posted on August 11, 2013 at 13:24 Comments Off on SummerScienceVideo: science is real
Aug08

12 year anniversary of angry letter to scientific journal editor

In: science politics • Tags: publishing

This year marks the 12th anniversary of the publication of this legendary letter to the editor in the Journal of systems and Software:

A letter from the frustrated author of a journal paper

R. L. Glass

Computing Trends, 1416 Sare Road, Bloomington, IN 47401, USA

Available online 28 September 2000.

Editor’s Note: It seems appropriate, in this issue of JSS containing the findings of our annual Top Scholars/Institutions study, to pay tribute to the persistent authors who make a journal like this, and a study like that, possible. In their honor, we dedicate the following humorous, anonymously-authored, letter!

—

Dear Sir, Madame, or Other:

Enclosed is our latest version of Ms. #1996-02-22-RRRRR, that is the re-re-re-revised revision of our paper. Choke on it. We have again rewritten the entire manuscript from start to finish. We even changed the g-d-running head! Hopefully, we have suffered enough now to satisfy even you and the bloodthirsty reviewers.

I shall skip the usual point-by-point description of every single change we made in response to the critiques. After all, it is fairly clear that your anonymous reviewers are less interested in the details of scientific procedure than in working out their personality problems and sexual frustrations by seeking some kind of demented glee in the sadistic and arbitrary exercise of tyrannical power over hapless authors like ourselves who happen to fall into their clutches. We do understand that, in view of the misanthropic psychopaths you have on your editorial board, you need to keep sending them papers, for if they were not reviewing manuscripts they would probably be out mugging little old ladies or clubbing baby seals to death. Still, from this batch of reviewers, C was clearly the most hostile, and we request that you not ask him to review this revision. Indeed, we have mailed letter bombs to four or five people we suspected of being reviewer C, so if you send the manuscript back to them, the review process could be unduly delayed.

Some of the reviewers’ comments we could not do anything about. For example, if (as C suggested) several of my recent ancestors were indeed drawn from other species, it is too late to change that. Other suggestions were implemented, however, and the paper has been improved and benefited. Plus, you suggested that we shorten the manuscript by five pages, and we were able to accomplish this very effectively by altering the margins and printing the paper in a different font with a smaller typeface. We agree with you that the paper is much better this way.

One perplexing problem was dealing with suggestions 13–28 by reviewer B. As you may recall (that is, if you even bother reading the reviews before sending your decision letter), that reviewer listed 16 works that he/she felt we should cite in this paper. These were on a variety of different topics, none of which had any relevance to our work that we could see. Indeed, one was an essay on the Spanish–American war from a high school literary magazine. The only common thread was that all 16 were by the same author, presumably someone whom reviewer B greatly admires and feels should be more widely cited. To handle this, we have modified the Introduction and added, after the review of the relevant literature, a subsection entitled “Review of Irrelevant Literature” that discusses these articles and also duly addresses some of the more asinine suggestions from other reviewers.

We hope you will be pleased with this revision and will finally recognize how urgently deserving of publication this work is. If not, then you are an unscrupulous, depraved monster with no shred of human decency. You ought to be in a cage. May whatever heritage you come from be the butt of the next round of ethnic jokes. If you do accept it, however, we wish to thank you for your patience and wisdom throughout this process, and to express our appreciation for your scholarly insights. To repay you, we would be happy to review some manuscripts for you; please send us the next manuscript that any of these reviewers submits to this journal.

Assuming you accept this paper, we would also like to add a footnote acknowledging your help with this manuscript and to point out that we liked the paper much better the way we originally submitted it, but you held the editorial shotgun to our heads and forced us to chop, reshuffle, hedge, expand, shorten, and in general convert a meaty paper into stir-fried vegetables. We could not – or would not – have done it without your input.

—

Journal of Systems and Software, Volume 54, Issue 1, 30 September 2000, Page 1

Nothing really has changed in a dozen years, it seems devilmad.png

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Posted on August 8, 2013 at 16:09 Comments Off on 12 year anniversary of angry letter to scientific journal editor
Aug06

Flashback: What can the spine teach us about learning?

In: blogarchives • Tags: conditioning, operant, response, spine, spontaneity, wolpaw

During my flyfishing vacation last year, pretty much nothing was happening on this blog. Now that I’ve migrated the blog to WordPress, I can actually schedule posts to appear when in fact I’m not even at the computer. I’m using this functionality to re-blog a few posts from the archives during the month of august while I’m away. This post is from April 29, 2011:

Only very few laboratories in the world perform operant conditioning of spinal reflexes. In fact, a quick PubMed search reveals there is only a single lab which has published in this field in the last decade, the lab of Jonathan Wolpaw. Jonathan’s review “What Can the Spinal Cord Teach Us about Learning and Memory?” in The Neuroscientist shows what neuroscience is missing out on by not investing more in this fascinating field.Operant conditioning of spinal reflexes is probably the most controlled operant conditioning situation imaginable: reward the animal when it responds with a reflex magnitude above or below a certain threshold, respectively. This is done by triggering the reflex with a cuff electrode around the nerve and then measuring the amplitude of the reflex with electromyography (EMG):

hreflex.png
The electrical stimulation via the cuff excites the muscle directly (the M signal in the EMG in the upper left corner) and, with a delay, indirectly via the H-reflex.

Below is an image of what that setup looks like when it’s implanted in a rat:
hreflex_rat.png
The rat is running around in its cage and receives a food reward whenever the H-reflex reaches the required amplitude.

Given that the textbook reflex (i.e., the spinal stretch reflex shown in the first image above) is monosynaptic, one would expect just this synapse to be modified after operant conditioning. However, this synaptic plasticity only contributes to one form of this learning, namely up-conditioning. Up-conditioning refers to the experiment where increased reflex amplitude was rewarded. In these experiments, the synaptic input from the primary 1a afferents (blue, in the first figure above) is increased, making the reflex amplitude larger. In down-conditioning, however, the synaptic input to the motor neuron is not altered, but the motor neuron itself (green) reveals an increased firing threshold and reduced postsynaptic potentials, making the motor neuron less likely to fire (and hence reflex amplitude smaller). In addition to these different forms of plasticity, correlates of the memory can be found throughout the spinal cord and even in the cortex. Some of these correlates appear to be compensatory modifications to other reflexes, preventing the increased amplitude of the conditioned reflex from making the animal limp. Again others are required for the maintenance of the memory, but do not seem to directly contribute to the memory trace itself. There are many more examples in the paper.

Taken together, the results presented in this review open up more questions than they answer and demonstrate that this is a promising research field, with still plenty of low-hanging fruit and a large variety of basic neuroscientific lessons which are hard, if not impossible to learn from other models.

What are you waiting for? Go and study operant conditioning of these reflexes already! smallgrin.png


Wolpaw, J. (2010). What Can the Spinal Cord Teach Us about Learning and Memory? The Neuroscientist, 16 (5), 532-549 DOI: 10.1177/1073858410368314

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Posted on August 6, 2013 at 18:01 Comments Off on Flashback: What can the spine teach us about learning?
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