Would a wiring diagram of the brain help you understand it?

Every budding chemist sits through a statistical mechanics course, in which the insanity and inutility of knowing the position and velocity of each and every of the 10^23 molecules of a mole or so of gas in a container is brought home.  Instead we need to know the average energy of the molecules and the volume they are confined in, to get the pressure and the temperature.

However, people are taking the first approach in an attempt to understand the brain.  They want a ‘wiring diagram’ of the brain. e. g. a list of every neuron and for each neuron a list of the other neurons connected to it, and a third list for each neuron of the neurons it is connected to.  For the non-neuroscientist — the connections are called synapses, and they essentially communicate in one direction only (true to a first approximation but no further as there is strong evidence that communication goes both ways, with one of the ‘other way’ transmitters being endogenous marihuana).  This is why you need the second and third lists.

Clearly a monumental undertaking and one which grows more monumental with the passage of time.  Starting out in the 60s, it was estimated that we had about a billion neurons (no one could possibly count each of them).  This is where the neurological urban myth of the loss of 10,000 neurons each day came from.  For details see https://luysii.wordpress.com/2011/03/13/neurological-urban-legends/.

The latest estimate [ Science vol. 331 p. 708 ’11 ] is that we have 80 billion neurons connected to each other by 150 trillion synapses.  Well, that’s not a mole of synapses but it is a nanoMole of them. People are nonetheless trying to see which areas of the brain are connected to each other to at least get a schematic diagram.

Even if you had the complete wiring diagram, nobody’s brain is strong enough to comprehend it.  I strongly recommend looking at the pictures found in Nature vol. 471 pp. 177 – 182 ’11 to get a sense of the  complexity of the interconnection between neurons and just how many there are.  Figure 2 (p. 179) is particularly revealing showing a 3 dimensional reconstruction using the high resolutions obtainable by the electron microscope.  Stare at figure 2.f. a while and try to figure out what’s going on.  It’s both amazing and humbling.

But even assuming that someone or something could, you still wouldn’t have enough information to figure out how the brain is doing what it clearly is doing.  There are at least 3 reasons.

l. Synapses, to a first approximation, are excitatory (turn on the neuron to which they are attached, making it fire an impulse) or inhibitory (preventing the neuron to which they are attached from firing in response to impulses from other synapses).  A wiring diagram alone won’t tell you this.

2. When I was starting out, the following statement would have seemed impossible.  It is now possible to watch synapses in the living brain of awake animal for extended periods of time.  But we now know that synapses come and go in the brain.  The various papers don’t all agree on just what fraction of synapses last more than a few months, but it’s early times.  Here are a few references [ Neuron vol. 69 pp. 1039 – 1041 ’11, ibid vol. 49 pp. 780 – 783, 877 – 887 ’06 ].  So the wiring diagram would have to be updated constantly.

3. Not all communication between neurons occurs at synapses.  Certain neurotransmitters are generally released into the higher brain elements (cerebral cortex) where they bathe neurons and affecting their activity without any synapses for them (it’s called volume neurotransmission)  Their importance in psychiatry and drug addiction is unparalleled.  Examples of such volume transmitters include serotonin, dopamine and norepinephrine.  Drugs of abuse affecting their action include cocaine, amphetamine.  Drugs treating psychiatric disease affecting them include the antipsychotics, the antidepressants and probably the antimanics.

Statistical mechanics works because one molecule is pretty much like another. This certainly isn’t true for neurons. Have a look at http://faculties.sbu.ac.ir/~rajabi/Histo-labo-photos_files/kora-b-p-03-l.jpg.  This is of the cerebral cortex — neurons are fairly creepy looking things, and no two shown are carbon copies.

The mere existence of 80 billion neurons and their 150 trillion connections (if the numbers are in fact correct) poses a series of puzzles.  There is simply no way that the 3.2 billion nucleotides of out genome can code for each and every neuron, each and every synapse.  The construction of the brain from the fertilized egg must be in some sense statistical.  Remarkable that it happens at all.  Embryologists are intensively working on how this happens — thousands of papers on the subject appear each year.

As my brain slowly recovers (or at least gets used to)  from the chemical assault on it by inhaled corticosteroids and muscarinic anticholinergic drugs, I’m having a lot of fun reading a book by Melanie Mitchell “Complexity: A Guided Tour” — but her view of neurons is simplistic in the extreme — hopefully that will improve in the last 100 pages.  A book review will follow.  The whole book is quite relevant to the question — just what would you accept as an explanation of how the brain does what it does?  The question leads into some deep philosophic minefields, but they can’t be avoided.  That’s for another time.

Hopefully, I’ll be able to get back to Anslyn and Dougherty in the coming week (after taxes).

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  • Curious Wavefunction  On April 11, 2011 at 5:57 pm

    Well, Ray Kurzweil thinks that we are not too far from reverse-engineering the brain; he cites recent single-neuron studies as proof of such progress. We may not be able to truly understand the brain but that does not mean we won’t ever be able to work wonders with it through its electrical, pharmacological and psychological stimulation.

    You may be interested in Roger Penrose’s book “The Emperor’s New Mind” in which he purports to demonstrate that the brain’s processes cannot be truly computable in the sense that a Turing machine is. Mitchell’s “Complexity” is an excellent book and I enjoyed especially reading the parts about chaos and biological scaling laws.

  • luysii  On April 11, 2011 at 9:17 pm

    I read Penrose’s book, interesting, but he got hornswoggled by someone into saying that neurotubules (found in all neurons) were quantum mechanical objects, hence indeterminate. A few physicists put things right showing that they were so large that their behavior was quite macroscopic.

    Please look at the Nature figure mentioned in the text if you can. I don’t see how this can be reversed engineered. Agree that the first 200 pages of Mitchell’s book is quite good, particularly the part about genetic algorithms. A book review will follow when I’ve finished it.

  • Curious Wavefunction  On April 11, 2011 at 11:45 pm

    Well, yes, Penrose says something to that effect which does not inspire confidence in his knowledge of biology. We are light years away from understanding the development of the brain, but in principle I don’t see why it would be much different from that of other organs. The key would be to understand how genes code for neuronal connectivity. After that things might be more tractable. Consider what happened when the genetic basis of antibody diversity was understood. It really opened the floodgates to understanding what were previously considered to be the mind-numbing complexities of the immune system.

  • luysii  On November 23, 2011 at 1:12 pm

    You can’t do better on delving into the way the brain is constructed than Science vol. 334 pp. 618 – 623 ’11. It has great pictures which demonstrate the complexity of brain organization, far better than thousands of words possibly can.

  • Johannes  On July 10, 2016 at 5:53 am

    “The construction of the brain from the fertilized egg must be in some sense statistical.”
    I believe you would be interested in “procedural generation” and the amazing things that have been done with that. Your argument sounds like “The program for Minecraft is smaller than all the billions of worlds generated with it, so it must be statistical.” While true on a certain level, this is also deeply uninformative. And the actual mechanism that generates the worlds is not really statistical itself.

    I also recommend “Gödel, Escher, Bach” for further reading into the matter of how to create complex things out of simple rules.

  • luysii  On July 10, 2016 at 2:36 pm

    Johannes — thanks for the input. Minecraft is a set of rules, the variation in structure comes from the variation in input from the players. What I meant by the comment, that brain construction must be in some sense statistical, is just the fact that connections between neurons can’t be completely specified the way transistors are linked on a chip. We have more neurons than nucleotides in the genome, so there’s no way the genome can even give each neuron a name, never mind about the information it takes to specifically wire neuron #1 to neuron #n.


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