Tag Archives: Oligodendrocyte

The wiring diagram of the brain takes another hit

Is there anything duller than wire? It conducts electricity. That’s about it. Copper wires conduct better than Aluminum wires. So what.  End of story. 

That’s pretty much the way we thought of axons, the wires of the nervous system. Thicker axons conduct faster than thin ones, and insulated axons conduct faster than non-insulated ones. The insulation is made out of fat and called myelin.  Just as fat in meat looks white, a bunch of axons sheathed by myelin looks white, which is how white matter got its name. 

Those of you old enough to remember vinyl records, know just how different a record sounds when played at the wrong speed.  That’s what an MS patient has to deal with.  The disease attacks white matter mostly, which means that when myelin is lost or damaged, nerve impulses slow down.  Information gets through, but it’s garbled. 

So we knew that losing myelin causes trouble, but other than that, it was assumed that myelin, once laid down by the cell producing it (the oligodendrocyte) was stable unless trauma or disease damaged it. 

That was until adaptive myelination came along roughly 10 years ago.  There is an excellent review [ Neuron vol. 109 pp. 1258 – 1273 ’21 ] which is irritating to read if you are looking for solid experimental facts.  This is not the fault of the authors.  They are trying to picture the frontier of a fast moving field.  By nature there is a lot of speculation in such an article, which would be a lot shorter (and duller) without it.  

However the following words occur frequently — could (43), has been understood (3), suggested (6), would (12), may (39) and is thought to (2).

The cells making the myelin are just that: cells.  Since the myelin they make is confined within them, a myelinated axon looks like a string of hot dogs, each dog the province of one oligo.  The space between the hot dogs is called the node (of Ranvier), and this is why myelinated axons conduct faster.  The impulse jumps between the nodes (saltatory conduction). 

Adaptive myelination comes in when you stimulate an axon — the myelin gets thicker, meaning that it conducts faster.   Also neuronal activity is held to alter myelin (the space between nodes gets longer meaning they conduct faster). 

Not all axons are myelinated, and activity ‘is thought to’ increase myelination of them. 

This has extremely profound consequences for how we think the brain works.  At the end of the post you’ll find an older one arguing that a wiring diagram of the brain (how the neurons are connected to each other) is far from enough to understand the brain.  But the article assumes that the wires are pretty much fixed in how they act. The Neuron article shows that this is wrong.  

Imagine if the connections between transistors on a computer chip, grew and shrunk depending on how much current flowed through them.   That appears to be the case for the brain.

Here’s the old post

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.