Glial Club

Sometime in 1997, two slightly rumpled academics (who’d rather be in the lab) are standing in a classroom introducing a unit on the “Physiology and Pharmacology of the Central Nervous System” to 30 rumpled undergrads (who’d rather be in bed).

A still from the hit musical neuroscience show, “Glial Club”

The lights are dimmed and a transparency is slipped on to the whirring projector. A bit of fiddling with the focus and the spartan text appears on screen:

What are “brain cells”?

Two types:

• Neurones¹
• Glial cells

As a member of the rumpled mass I copy these words onto my notepad, adding “- around 90% of all brain cells, from Greek for ‘glue’, provide nutrients for neurones, other housekeeping functions” to the “glial cells” bullet point, in accordance with the words of the lecturer.

And so it came to pass that glial cells feature at the top of the page of the first notes I ever took in the first class I ever took on neuroscience. They didn’t get another look-in at any other point during my brief and unglittering academic career.

No, when it came to the brain we were interested in the 100 billion neurones that, we were told, send all the information buzzing around the brain and make us who we are. Glial cells were viewed by neuroscientists as, at worst, the cranial concrete into which the neuronal wiring is laid and, at best, neurones’ housekeepers.

How times change. Over the last 15 years scientists have realised that glial cells hold considerable sway in how the whole house is run; there hardly seems to be a decision taken where they don’t have some influence.

This is particularly true where glutamate is involved. Glutamate is a neurotransmitter – a substance that neurones use to communicate with each other. It is, in fact, the most common neurotransmitter in the central nervous system, but in sufficient quantity will overexcite and kill nerve cells.

In most cases, neurones can sufficiently absorb and “defuse” glutamate molecules themselves but often they need a little help in mopping up the mess of neurotransmission and this function is performed by glial cells called astrocytes.

Still, even if astrocytes save neurones’ lives by doing this, it’s in keeping with their traditional, boring (if they don’t mind me saying so) jobs as housekeepers.

But a few months after my first attendance at a neuroscience lecture scientists discovered that astrocytes can not only absorb glutamate but they can release it too. This is “gliotransmission”, which sees glial cells communicating with neurones (glutamate isn’t the only gliotransmitter) and thus exerting a direct influence on the relay of information in the brain. In short, it’s not all about the neurones.

So even though the importance of gliotransmission is a hotly debated topic, things are much more complicated than when I was a pharmacology undergrad. Back then, when you talked about synapses in the brain you meant a simple interface where one neurone released a neurotransmitter to influence the activity of another².

A diagram of a “bipartite synapse”: this is the kind of diagram that can be found in every basic neuroscience textbook on earth

Now glial cells are involved and it’s a ménage à trois known as the “tripartite synapse”. This arrangement is further complicated by the fact that some astrocytes have glutamate receptors on their cell surfaces, so they are capable not only of regulating and releasing neurotransmitters but will respond to them as well.

Furthermore, now when you say “synapse in the brain”, you might not even be referring to this kind of synapse at all. You might be talking about glial cell-only synapses. For with the former housekeeper’s rise in status has come greater interest in the “other brain”, where only glial cells are involved.

That’s right, glial cells have their own exclusive communication networks although, truth be told, the interfaces between cells are more often referred to as “gap junctions” than “synapses”³. Here, cells are joined by channels which, when opened, allow specific ions or chemical compounds to pass through.

Gap junctions thus allow for a more direct kind of communication than neurotransmitter-mediated, neurone-to-neurone synapses do. This means that if the right channels are open and enough glial cells are joined together impulses can run across a large number of interconnected cells (“cell networks”), much like a Mexican wave rolling across seating sections in a stadium.

This kind of long-range stimulus transmission has been shown to occur across astrocyte networks and has led a few neuroscientists into some distinctly philosophical conjecture.

Take a deep breath. We’re about to dive headlong into that mystery of mysteries: consciousness. More exactly the question of how, with all the different parts of the brain performing their varied functions simultaneously, people are possessed of one unifying consciousness rather than several.

What ties all the work of the brain together? Could it be these astrocyte networks?

This from a review paper in Progress in Neurobiology published last year:

As waves propagate through gap junctions and reach other types of astrocytes, the active [astrocyte] network functions as a “Master Hub” that integrates results of distributed processing from several brain areas and supports conscious states.

OK, I overdid the lead-in hyperbole a little bit, but using words like “Master Hub” (capitalised in the text!) and “conscious states” in the same sentence is a tease, to say the least.

Rene Descartes: The enlightenment philosopher is overjoyed to be mentioned in My Last Nerve again

As I mentioned in a previous post, the hub that integrates the varied results of neural processing to create a unified consciousness was the holy grail of neuroscience for 300 years. René Descartes, the first crusader, thought he’d found the sacred object in the pineal gland. He hadn’t of course, and the other similarly unsuccessful  searches that followed led to the quest being abandoned sometime during the last century. By the time the millennium rolled around, the consciousness hub had been dismissed as a myth.

But who knows, astrocyte networks may well be the long-forgotten grail, or at least the key to the door to the chamber in the cave that houses it. I’m a bit dubious, but I ain’t no neuroscientist.

In any case, such conjecture shows how far glial cells have risen in neuroscientists’ estimation since the days when they merited a one minute mention in a year-long lecture series on the workings of the brain.

Postscripts:

Neuroskeptic wrote an excellent post on glial cells a little while ago (actually a review of “The Other Brain” book linked in my piece) which covers similar ground to the above, minus the meanderings on consciousness. If you’re not already familiar with that site I exhort you to go and have a gander.

I ran out of time to write about it but the news item that inspired this post was “Protein dose reverses learning problems in Down’s mice”, a story that featured on New Scientist’s webpages. It was a reasonably complicated study which I’m not going to relay again here but, suffice to say, glial cells are involved. Animal studies are often over-hyped (things are always a bit different in human beings) but I found that one really intriguing.

Notes:

1. Yes, that’s right – neurone, ends with an ‘e’. I come over all anglocentric and snooty whenever I see the increasingly employed, Americanised, six-letter version of that word. It’s pathetic, I know.
2. There being something like 100 trillion synapses in the brain means that thinking about neurones in terms of one-on-one interactions is so simplistic as to be meaningless. Still, that’s the paradigm we were given to work with.
3. Nonetheless, gap junctions are synapses, electrical synapses. On the other hand, the classical neurone-to-neurone, neurotransmitter-mediated synapses are chemical synapses.

Image credits: Glee by “Dani3l Cipras” (Wikimedia Commons), Synapse diagram by Stephen Taylor (Flickr)

References:

Volterra, A., Bezzi, P., Carmignoto, G., Pasti, L., Vesce, S., Rossi, D., Rizzini, B., & Pozzan, T. (1998). Prostaglandins stimulate calcium-dependent glutamate release in astrocytes Nature, 391 (6664), 281-285 DOI: 10.1038/34651

Pereira Jr, A., & Furlan, F. (2010). Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity Progress in Neurobiology, 92 (3), 405-420 DOI: 10.1016/j.pneurobio.2010.07.001