Related to: Brain Breakthrough! It's Made of Neurons!



I can't really recommend Andrew Koob's The Root of Thought. It's poorly written, poorly proofread, lacking much more information than is in the Scientific American review, and comes across as about one part neuroscience to three parts angry rant. But it does present an interesting hypothesis and an interesting case study on a major failure of rationality.



Only about ten percent of the brain is made of neurons; the rest is a diverse group of cells called "glia". "Glia" is Greek for glue, because the scientists who discovered them decided that, since they were in the brain and they weren't neurons, they must just be there to glue the neurons together. Since then, new discoveries have assigned glial cells functions like myelination, injury repair, immune defense, and regulation of blood flow: all important, but mostly things only a biologist could love. The Root of Thought argues that glial cells, especially a kind called astrocytes, are also important in some of the higher functions of thought, including memory, cognition, and maybe even creativity. This is interesting to neuroscientists, and the story of how it was discovered is also interesting to us as aspiring rationalists.

Glial cells involved in processing

Koob's evidence is indirect but suggestive. He points out that more intelligent animals have a higher astrocyte to neuron ratio than less intelligent animals, all the way from worms with one astrocyte per thirty neurons, to humans with an astrocyte: neuron ratio well above one. Within the human brain, the areas involved in higher thought, like the cortex, are the ones with the highest astrocyte:neuron ratio, and the most down-to-earth, like the cerebellum, have barely any astrocytes at all. Especially intelligent humans may have higher ratios still: one of the discoveries made from analyzing Einstein's brain was that he had an unusually large number of astrocytes in the part of his brain responsible for mathematical processing. And learning is a stimulus for astrocyte development. When canaries learn new songs, new astrocytes grow in the areas responsible for singing.



Astrocytes have a structure especially suited for learning and cognition. They have their own gliotransmitters, similar in function to neurotransmitters, and they communicate with one another, sparking waves of astrocyte activity across areas of the brain. Like neurons, they can enter an active state after calcium release, but unlike neurons, which get calcium only when externally activated, astrocytes can fill with calcium either because of external stimuli or when their own calcium stores randomly leak out into the cell, a process which resembles the random, unprovoked nature of thought during sensory deprivation and dreaming.



Astrocytes also affect and are affected by neurons. Each astrocyte "monitors" thousands of synapses, and releases calcium based on the input it receives. Output from astrocytes, in turn, affects the behavior of neurons. Astrocytes can take up or break down neurotransmitters, which changes the probability of nearby neurons activating, and they can alter synapses, promoting some and pruning others in a process likely linked to long-term potentiation in the brain.



Although it wasn't in the book, very recent research shows a second type of glial cell, the immune-linked microglia, play a role in behavior that may be linked to obsessive-compulsive disorder; a microglia-altering bone marrow transplant cures an OCD-like disease in mice.



By performing computations that influence the firing of neurons, glial cells at the very least play a strong supporting role in cognition. Koob goes way beyond that (and really beyond what he can support) and argues that actually neurons play a supporting role to glia, being little more than the glorified wires that relay astroglial commands. His argument is very speculative and uses words like "could" a lot, but the evidence at least shows that glia are more important than a century of neurology has given them credit for.



We don't know how much we don't know about cognitive science



Previous Less Wrong articles, for example Artificial Addition, have warned against trying to replicate a process without understanding it by copying a few surface features. One of the most popular such ideas is to replicate the brain by copying the neurons and seeing what happens. For example, IBM's Blue Brain project hopes to create an entire human brain by modeling it neuron for neuron, without really understanding why brains work or why neurons do what they do1.



We've made a lot of progress in cognitive science in the past century. We know where in the brain various activities take place, we know the mechanisms behind some of the more easily studied systems like movement and perception, and we've started researching the principles of intelligence that the brain must implement to do what it does. It's tempting to say that we more or less understand the brain, and the rest is just details. One of the take-home messages from this book is that, although cognitive scientists can justifiably be proud of their progress, our understanding still hasn't even met the low bar of being entirely sure we're even studying all the right kinds of cells, and this calls into question our ability to meet the higher bar of being able to throw what we know into a simulator and hope it works itself out.



A horrible warning about community irrationality



In the late 19th century, microscopy advanced enough to look closely at the cellular structure of the brain. The pioneers of neurology decided that neurons were interesting and glia were the things you had to look past to get to the neurons. This theory should have raised a big red flag: Why would the brain be filled with mostly useless cells? But for about seventy five years, from the late 19th century to the mid to late 20th, no one seriously challenged the assumption that glia played a minor role in the brain.



Koob attributes the glia's image problem to the historical circumstances of their discovery. Neurons are big, peripherally located, and produce electrical action potentials. This made them both easy to study and very interesting back in the days when electricity was the Hot New Thing. Scientists first studied neurons in the periphery, got very excited about them, and later followed them into the brain, which turned out to be a control center for all the body's neurons. This was interesting enough that neurologists, people who already had thriving careers in the study of neurons, were willing to overlook the inconvenient presence of several other types of cells in the brain, which they relegated to a supporting role. The greatest of these early pioneers of neurology, Santiago Ramon y Cajal, was the brother of the neurologist who first proposed the idea that glial cells functioned as glue and may have (Koob theorizes) let familial loyalty influence his thinking. The community took his words as dogma and ignored glia for years, a choice no doubt made easier by all the exciting discoveries going on around neurons. Koob discussed the choice facing neuroscientists in the early 20th century: study the cell that seemed on the verge of yielding all the secrets of the human mind, or tell your advisor you wanted to study glue instead. Faced with that decision, virtually everyone chose to study the neurons.



There wasn't any sinister cabal preventing research into glia. People just didn't think of it. Everyone knew that neurons were the only interesting type of cell in the brain. They assumed that if there was some other cell that was much more common and also very important, somebody would have noticed. I've read neuroscience books, I read the couple of paragraphs where they mentioned glial cells, and I shrugged and kept reading, because I assumed if they were hugely important somebody would have noticed.



The heuristic, that an entire community doesn't just miss low-hanging fruit, is probably a good one and as many people have pointed out the vast majority of people who think they've found something that the scientific community has missed are somewhere between wrong and crackpot. Science is usually pretty good at finding and recognizing its mistakes, and even in the case of glial cells they did eventually find and recognize the mistake. It just took them a century.



One common theme across Less Wrong and SIAI is that there are some relatively little-known issues that, upon a moderate amount of thought, seem vitally important. And one of the common arguments against this theme is that if this were true, surely somebody would have noticed. The lesson of glial cells is that sometimes this just doesn't happen.

Related: Glial Cells: Their Role In Behavior, Underappreciated Star-Shaped Cells May Help Us Breathe, Glial Cells Aid Memory Formation, New Role For Supporting Brain Cells, Support Cells, Not Neurons, Lull Brain To Sleep