Canonical circuits in neuroscience

Gary Marcus, Adam Marblestone, and Thomas Dean have a nice perspective piece in Science this week on the atoms of neural computation (gated):

One hypothesis is that cortical neurons form a single, massively repeated “canonical” circuit, characterized as a kind of a “nonlinear spatiotemporal filter with adaptive properties”. In this classic view, it was “assumed that these…properties are identical for all neocortical areas.” Nearly four decades later, there is still no consensus about whether such a canonical circuit exists, either in terms of its anatomical basis or its function. Likewise, there is little evidence that such uniform architectures can capture the diversity of cortical function in simple mammals, let alone characteristically human processes such as language and abstract thinking…

What would it mean for the cortex to be diverse rather than uniform? One possibility is that neuroscience’s quarry should be not a single canonical circuit, but a broad array of reusable computational primitives—elementary units of processing akin to sets of basic instructions in a microprocessor—perhaps wired together in parallel, as in the reconfigurable integrated circuit type known as the field-programmable gate array.

Candidate computational primitives might include circuits for shifting the focus of attention, for encoding and manipulating sequences, and for normalizing the ratio between the activity of an individual neuron and a set of neurons. These might also include circuits for switching or gating information flow between different parts of cortex, and for working memory storage, decision-making, storage and transformation of information via population coding and the manipulation and encoding of variables, alongside machinery for hierarchical pattern recognition…

And so on. People have long proposed that ‘all cortex is the same’ or some such rubbish, it being all made of cortical columns that are the same from one bit of tissue to another. I’m not sure how many people really believe that, but you see the statement a lot (and it is a big reason people studying visual cortex claim they’re just interested in ‘cortex’).

Of course, on a smaller scale there has been a long interest in more primitive ‘microcircuits’. A few examples:

The Reichardt (motion) detector:

Reichardt detector

There is strong experimental evidence for this in drosophila (the fly), and is a repeated motif across visual space.

(see source for review)

Inhibitory circuit motifs:


(see source)

Circuit motif for flexible categorization:

flexible categorization motif

(see source)

Since we know all the circuitry of the worm C. elegans, you can look at which motifs are overrepresented:

c elegans 4 neuron circuit motifs

(see source)

Qian, J., Hintze, A., & Adami, C. (2011). Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain PLoS ONE, 6 (3) DOI: 10.1371/journal.pone.0017013

Borst, A. (2007). Correlation versus gradient type motion detectors: the pros and cons Philosophical Transactions of the Royal Society B: Biological Sciences, 362 (1479), 369-374 DOI: 10.1098/rstb.2006.1964

Pfeffer, C. (2014). Inhibitory Neurons: Vip Cells Hit the Brake on Inhibition Current Biology, 24 (1) DOI: 10.1016/j.cub.2013.11.001

Mysore, S., & Knudsen, E. (2012). Reciprocal Inhibition of Inhibition: A Circuit Motif for Flexible Categorization in Stimulus Selection Neuron, 73 (1), 193-205 DOI: 10.1016/j.neuron.2011.10.037

Marcus, G., Marblestone, A., & Dean, T. (2014). The atoms of neural computation Science, 346 (6209), 551-552 DOI: 10.1126/science.1261661


psychohydraulic model

On twitter, @mnxmnkmnd pointed me to Lorenz’ model of ‘psychohydraulics‘ as a theory of behavior. Wut?

From a book chapter (I can’t figure out which book):

Lorenz introduced the (artificial) concept of an action-specific energy, ac- cumulating in a tank with a valve. In this model, the level of action-specific energy is raised as a result of the passage of time (if the behavior is not being executed), leading to the eventual opening of the valve, and the flow of action-specific energy into a bucket with several holes on different levels, represent- ing different aspects of the behavior in question. The flow of action-specific behavior into the bucket can also be increased by external factors, represented by weights on a scale, connected to the valve by means of a string. As the energy flows into the bucket, the low-threshold parts of the behavior are im- mediately expressed, and higher-threshold aspects are expressed if the level of energy reaches sufficiently high. Before proceeding with a simple set of equations for this model, one should note that the modern view of motivation is more complex than the simple feedback model just described.

Wut? Here’s some equations, because that makes everything easier to understand:


Remember, they’re talking about animal motivation. This is what happens when you win a Nobel prize.

Here is more explanation and digressions.

Emodiversity: why a mix of emotions is good for you

Neuroskeptic covered a paper (pdf) that postulates that it is healthiest to have a mix of emotions:

It turns out that emotional diversity was a good thing (in terms of being associated with less depression etc.) for both positive and for negative emotions. This seems a little counter-intuitive. You might have expected that feeling many negative emotions would be worse than only feeling one of them – but in fact, it’s better.

The authors speculate that it could be due to the same resilience that biodiversity confers. They also suggest:

experiencing many different specific emotional states (e.g., anger, shame, and sadness) may have more adaptive value than experiencing fewer and/or more global states (e.g., feeling bad), as these specific emotions provide richer information about which behavior in one’s repertoire is more suited for dealing with a given affective situation

One way to think about this is to begin by asking, what are emotions for? Emotions provide instant and powerful information when making decisions. They have access to long-term experience as well as the internal state of the animal (think: HANGRY!). Famously, patients with mPFC damage are ‘overly-logical’ and, consequently, make very poor decisions; there’s just not enough information in the world to make Spock-like decisions all the time!

In a review we published recently (pdf), we discussed the possibility that emotions are a way of properly responding to information in the world. When you’re in a good mood, you’re more responsive to positive stimuli. Conversely, when you’re in a bad mood, you’re more responsive to negative stimuli. Therefore, if you want to respond to the world optimally, you’ll need the right mix of moods for the right environment: emodiversity.

Monday open question: Which neuroscientists have most influenced your thinking?

With the release of the NIH BRAIN Initiative grants, it’s become clear that there’s a big disconnect between members of the different subfields: people working molecular neuroscience, cognitive neuroscience, systems neuroscience, etc. I’m just as bad as anyone else so I thought it may be useful to know who are the, say, five most important influences to their work?

For me, the names would have to be (in no particular order):

1. Eve Marder

2. Bill Bialek

3. Rachel Wilson

4. Krishna Shenoy/Mark Churchland

5. Cori Bargmann

Unrelated to all that, 10/12 edition

The Big Problem With Mini-Pigs

mini pig behind bars

In 2012, as a favor to a friend, Canadians Steve Jenkins and Derek Walter adopted a three-pound (1.4-kilogram) “mini-pig” named Esther. Or so they thought. Within two years Esther wasn’t so mini. In fact, she weighed 500 pounds (227 kilograms). “We didn’t want to believe it,” says Jenkins, “but at four months it became painfully obvious she would be larger than we thought. She grew about three-fourths of a pound a day. And she’s still growing now.” Like thousands of others before them, Jenkins and Walter had been duped into thinking that their tiny pig would stay tiny—perhaps small enough to fit in a teacup—and make as good a house pet as any dog or cat…

To keep the animals’ size down, many breeders have been inbreeding and underfeeding their pigs, telling buyers that piglets are actually adults, or—as in Esther’s case—passing off commercial pigs originally intended for food as a smaller breed of pig…To keep costs down Hoyle has learned to do routine veterinary procedures himself—a common strategy among sanctuary owners. He gives enemas to pigs that overindulge on acorns, trims their tusks and hoofs, and occasionally lances abscesses.

Whoever makes the first genetically-engineered PermaKitten is going to be a billionaire.

The Limits of Friendship

The Dunbar number is actually a series of them. The best known, a hundred and fifty, is the number of people we call casual friends—the people, say, you’d invite to a large party. (In reality, it’s a range: a hundred at the low end and two hundred for the more social of us.) From there, through qualitative interviews coupled with analysis of experimental and survey data, Dunbar discovered that the number grows and decreases according to a precise formula, roughly a “rule of three.” The next step down, fifty, is the number of people we call close friends—perhaps the people you’d invite to a group dinner. You see them often, but not so much that you consider them to be true intimates. Then there’s the circle of fifteen: the friends that you can turn to for sympathy when you need it, the ones you can confide in about most things. The most intimate Dunbar number, five, is your close support group. These are your best friends (and often family members). On the flipside, groups can extend to five hundred, the acquaintance level, and to fifteen hundred, the absolute limit—the people for whom you can put a name to a face. While the group sizes are relatively stable, their composition can be fluid. Your five today may not be your five next week; people drift among layers and sometimes fall out of them altogether.

I can barely believe these are real

Continue reading

Kavli Prize

Looks like it’s science prize week on neuroecology… I missed that the Kavli prize winners were announced earlier this month. The Kavli Prize goes to researchers in astrophysics, nanophysics, and neuroscience (yeah, I don’t get the connection either.)

This year’s neuroscience winners are Brenda Milner, John O’Keefe, and Marcus E. Raichle “for the discovery of specialized brain networks for memory and cognition.” The summaries of their work:

Brenda Milner discovered regions of the brain specialized for memory formation and other cognitive functions.  She found that HM, a neurological patient with damage to the hippocampus and surrounding regions, could not acquire new memories of events, but could speak, reason and recall long-past memories.

John O’Keefe discovered that the hippocampus contains neurons that encode an animal’s specific location. These place cells allow detection of novelty and changes in familiar environments and collectively form a cognitive map critical for animal navigation behaviour.

Marcus E. Raichle designed methods for visualizing the activity of the normal living human brain. These techniques permitted the quantitative measurements of blood flow and metabolism in localized regions of the brain and provided the basis for all modern functional imaging studies.

Nature Reviews Neuroscience has an interview with the three winners (paywall, sadly). This left me flabbergasted:

In 1936, I went to Cambridge University to study mathematics but soon realized that I would never distinguish myself in that field. I thought of switching to philosophy because I was still attracted to the study of logic but my colleagues advised me to try experimental psychology instead, since it would be easier to find a job afterwards. It turned out to be a very good choice.

1936?! And this woman is still receiving awards? I don’t know whether to be proud of her or terrified. Interestingly, two of the three winners specifically mentioned their interest in philosophy. How many would these days?



Nobel Prizes in Neuroscience (Updated)

After O’Keefe and the Mosers winning the Nobel prize this year, I was wondering how many of the prizes have been for neuroscience research (directly). From the full list, these seem to be the winners:

  1. The Nobel Prize in Physiology or Medicine 2014
    John O’Keefe, May-Britt Moser and Edvard I. Moser
    “for their discoveries of cells that constitute a positioning system in the brain”
  2. The Nobel Prize in Physiology or Medicine 2013
    James E. Rothman, Randy W. Schekman and Thomas C. Südhof
    “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells”
  3. The Nobel Prize in Physiology or Medicine 2004
    Richard Axel and Linda B. Buck
    “for their discoveries of odorant receptors and the organization of the olfactory system”
  4. The Nobel Prize in Physiology or Medicine 2000
    Arvid Carlsson, Paul Greengard and Eric R. Kandel
    “for their discoveries concerning signal transduction in the nervous system”
  5. The Nobel Prize in Physiology or Medicine 1991
    Erwin Neher and Bert Sakmann
    “for their discoveries concerning the function of single ion channels in cells”
  6. The Nobel Prize in Physiology or Medicine 1981
    Roger W. Sperry
    “for his discoveries concerning the functional specialization of the cerebral hemispheres”
    David H. Hubel and Torsten N. Wiesel
    “for their discoveries concerning information processing in the visual system”
  7. The Nobel Prize in Physiology or Medicine 1977
    Roger Guillemin and Andrew V. Schally
    “for their discoveries concerning the peptide hormone production of the brain”
    Rosalyn Yalow
    “for the development of radioimmunoassays of peptide hormones”
  8. The Nobel Prize in Physiology or Medicine 1973
    Karl von Frisch, Konrad Lorenz and Nikolaas Tinbergen
    “for their discoveries concerning organization and elicitation of individual and social behaviour patterns”
  9. The Nobel Prize in Physiology or Medicine 1971
    Earl W. Sutherland, Jr.
    “for his discoveries concerning the mechanisms of the action of hormones”
  10. The Nobel Prize in Physiology or Medicine 1970
    Sir Bernard Katz, Ulf von Euler and Julius Axelrod
    “for their discoveries concerning the humoral transmittors in the nerve terminals and the mechanism for their storage, release and inactivation”
  11. The Nobel Prize in Physiology or Medicine 1963
    Sir John Carew Eccles, Alan Lloyd Hodgkin and Andrew Fielding Huxley
    “for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane”
  12. The Nobel Prize in Physiology or Medicine 1961
    Georg von Békésy
    “for his discoveries of the physical mechanism of stimulation within the cochlea”
  13. The Nobel Prize in Physiology or Medicine 1950
    Edward Calvin Kendall, Tadeus Reichstein and Philip Showalter Hench
    “for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects”
  14. The Nobel Prize in Physiology or Medicine 1949
    Walter Rudolf Hess
    “for his discovery of the functional organization of the interbrain as a coordinator of the activities of the internal organs”
    Antonio Caetano de Abreu Freire Egas Moniz
    “for his discovery of the therapeutic value of leucotomy in certain psychoses”
  15. The Nobel Prize in Physiology or Medicine 1947
    Carl Ferdinand Cori and Gerty Theresa Cori, née Radnitz
    “for their discovery of the course of the catalytic conversion of glycogen”
    Bernardo Alberto Houssay
    “for his discovery of the part played by the hormone of the anterior pituitary lobe in the metabolism of sugar”
  16. The Nobel Prize in Physiology or Medicine 1944
    Joseph Erlanger and Herbert Spencer Gasser
    “for their discoveries relating to the highly differentiated functions of single nerve fibres”
  17. The Nobel Prize in Physiology or Medicine 1936
    Sir Henry Hallett Dale and Otto Loewi
    “for their discoveries relating to chemical transmission of nerve impulses”
  18. The Nobel Prize in Physiology or Medicine 1932
    Sir Charles Scott Sherrington and Edgar Douglas Adrian
    “for their discoveries regarding the functions of neurons”
  19. The Nobel Prize in Physiology or Medicine 1906
    Camillo Golgi and Santiago Ramón y Cajal
    “in recognition of their work on the structure of the nervous system”
  20. The Nobel Prize in Physiology or Medicine 1904
    Ivan Petrovich Pavlov
    “in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged”

16.2% 19% of the awards have gone to neuroscience!

One thing that struck me is how many names I don’t know, especially for people who, apparently, did really foundational work. I need to bone up on my history of neuroscience. Also, neuroscientists, don’t expect another award for ~7-8 years (*coughDeisserothBoydencough*).

*I’m including the 1973 prize as the (lone?! update: Pavlov!) psychology prize. Not sure whether to include the 1994 prize for GPCRs?

Updated: As commenter alf pointed out, I forgot Golgi and Ramon y Cajal! Which is depressing. And he’s right, last year’s work on vesicular transport could largely be seen as a neuroscientific prize.

Also Pavlov, because of the weird way the committee described his work.

Orangutan facts

They’re surprisingly smart:

“They say that if you give a chimpanzee a screwdriver, he’ll break it; if you give a gorilla a screwdriver, he’ll toss it over his shoulder; but if you give an orangutan a screwdriver, he’ll open up his cage and walk away.”

At Camp Leakey, the orangutans had plenty of opportunity to observe and imitate people. They soon developed a habit of stealing canoes, paddling them downriver, and abandoning them at their destinations. Even triple and quadruple knots in the ropes securing the canoes to the dock did not deter the apes. Over the years, they have also learned to brush their teeth, bathe themselves, wash clothes, weed pathways, wield saws and hammers, and soak rags in water in order to cool their foreheads with them. And they have done all of this without any instruction.

They’re also social:

But it turns out that adult female relatives stick together: they have overlapping ranges and periodically interact. “I grew up in rural Saskatchewan,” Russon, who now works and teaches at York University, in Toronto, told me. “And, for me, that is exactly what orangutan social life is like. There are communities, but they are very broadly dispersed. It might be fifteen miles to your cousin’s place, or another twenty miles to the next nearest relative, but everybody knows everybody.” Adolescent orangutans—curious and audacious—regularly make new friends. These wandering youngsters, vaulting from one tree to the next, are likely the torchbearers of orangutan culture.

Here is a paper on social behavior of Orangutans:

As they grew older males increasingly spent less time making physical contact, but the amount of time they spent in proximity (within arm’s length) to others increased. Adult females regularly played with other group members. Contact, allogrooming, and social play showed nonrandom relationships between individuals. Adult females showed the most allogrooming and contact, adolescent and subadult males the most play. There was no obvious dominance hierarchy. One adult male spent about 10% of his time walking around the perimeter of the island. One-year-old infants rarely interacted with other individuals apart from their own and the other infant’s mother. While orangutans lead relatively solitary lives in nature, it was concluded that the opportunities for social contact and play provided by the SZG orangutan island were beneficial to this species in captivity.

[Photo by George]

The 2014 Nobel Prize in Medicine and Physiology goes to the discoverers of grid and place cells

I was joking last night that when they announced the Nobel Prize, I wouldn’t have any clue who the winner was because I basically don’t know biology from before 10 years ago. Then I wake up and the winners are systems neuroscientists. That’ll teach me to joke! Obviously, I am ecstatic.

John O’Keefe, who discovered place cells, and May-Britt and Edvard Moser, who discovered grid cells, shared the prize.

Here is the announcement. Here is a fortuitously-timed profile on the Mosers (great, must read). Here is the New York Times (currently pretty sparse, but better than The Economist). Here is an adorable piglet running through the grass.

The two O’Keefe papers that you should know are: “The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat” and “Place units in the hippocampus of the freely moving rat.” Sadly, neither are Open Access.

The Moser paper is obviously their 2005 result “Microstructure of a spatial map in the entorhinal cortex“. This is one of those cases where the data is so beautiful you can’t believe it’s real (it is):

grid cellsNone of these papers are Open Access. Given that they won the Nobel Prize, they all should be. Surely the committee can afford that?


Unrelated to all that, 10/4 edition

The curse of committees and clubs

First, the average scientist today is not of the quality of our predecessors; it’s a bit analogous to the so-called “greatest generation” of men and women of the United States who fought off fascism in World War II compared with their baby boomer children. Biomedical research is a huge enterprise now; it attracts riff-raff who never would have survived as scientists in the 1960s and 1970s. There is no doubt that highly capable scientists currently participate in the grant-review process. Likewise, unfortunately, study sections are undoubtedly contaminated by riff-raff.

Hilarious troll is hilarious. Don’t think it was intentional, though. Via drugmonkey

Frog TV

How much better are we, really?

Hamilton’s Rule and Its Discontents

In an incendiary 2010 Nature article, M. A. Nowak, C. E. Tarnita, and E. O. Wilson present a savage critique of the best-known and most widely used framework for the study of social evolution, W. D. Hamilton’s theory of kin selection. More than a hundred biologists have since rallied to the theory’s defence, but Nowak et al. maintain that their arguments ‘stand unrefuted’. Here I consider the most contentious claim Nowak et al. defend: that Hamilton’s rule, the core explanatory principle of kin selection theory, ‘almost never holds’. I first distinguish two versions of Hamilton’s rule in contemporary theory: a special version (HRS) that requires restrictive assumptions, and a general ver- sion (HRG) that does not. I then show that Nowak et al. are most charitably construed as arguing that HRS almost never holds, while HRG buys its generality at the expense of explanatory power. While their arguments against HRS are fairly uncontroversial, their arguments against HRG are more contentious, yet these have been largely overlooked in the ensuing furore. I consider the arguments for and against the explanatory value of HRG, with a view to assessing what exactly is at stake in the debate. I suggest that the debate hinges on issues concerning the causal interpretability of regression coefficients, and concerning the explanatory function Hamilton’s rule is intended to serve.

We truly live in a golden age for toddlers and bored Red Robin diners


Crayola colors

There’s apparently a research article in the Russian Journal of Genetic Genealogy on my ancestral clan

The clans are one of the Scottish national traditions – large groups of families, bearing usually one surname and origin from a hypothetical common ancestor. One of these Clans is the western highland Clan Colquhoun; many members of this clan now live in UK, USA,Canada, Australia, New Zealand and other countries.

tl;dr There are two main lineages; one reaching back to ~1200 AD from the initial Colquhoun, Humphrey de Kilpatrick, and one ~1700 AD to James Grant (who took over as when his father-in-law had no more natural male heirs). Incidentally, I am in the de Kilpatrick lineage. Genetics! They work.

Do old folks love coffee more than youngsters?

coffee consumption

Note: they don’t correct for weight

Beautiful city-slices