readings> glial cells

Glial cells continue to titillate neuroscientists. For there is nothing like the thrill of over-turning orthodoxy. Ever since Cajal and Sherrington it has been a truism that we are just a pack of neurons, a tracery of synaptic connections. All the action lies in the humming fibres of dendrites and axons; with glia being merely so much brain packing. But in the 1990s researchers started suggesting glial cells might also be woven into the brain’s information processing pathways, raising the delicious prospect that our already immensely complex neural machinery could instantly become at least several orders of magnitude more labyrinthine.

What sparked interest was the discovery of calcium waves propagating from astrocyte to astrocyte. It was already known that astrocytes and oligodendrocytes had both ion channels and also receptors sensitive to neurotransmitters such as glutamate, noradrenaline and GABA (gamma aminobutyric acid). However this was explained away as being in keeping with a general housekeeping and maintenance role. The main chore of astrocytes was supposed to be to recycle excess glutamate around synaptic junctions. But in 1990, Steven Smith at Yale University stimulated a culture of hippocampal astrocytes with glutamate and observed a pulse of calcium release which passed across 59 cells before fading. Sure the pulse was slow – taking seconds rather than milliseconds – but it looked like proper cell-to-cell signalling.

Cue massive speculation about glial cells as the neglected half of the brain. Glia make up more than 50 percent of the brain’s volume and outnumber neurons by 9 to 1. Rats in enriched environments grow more glia as well as dendrites. Famously, Albert Einstein’s left inferior parietal lobule had also been found to have 70 percent more glial cells than usual (even though his prefrontal cortex was described as thin and overall his brain 200 grams smaller than average!). So perhaps glia were just as much part of the brain’s networks as neurons.

It’s only half-time in the current glia research effort and so rather early to pronounce a verdict. However there does seem truth in the idea that glia are indeed part of the processing fabric – not passive metabolic support but part of the brain’s active intellectual response.

The calcium waves have been observed in oligodendrocytes as well as astrocytes. The evidence suggests the waves are spread not just by simple direct membrane contact but triggered by transmitters like glutamate and adenosine. The connections are also selective in that some neighbouring cells may react while others don’t. Most significantly, there is two-way communication between glia and neurons, allowing precise feedback networks.

So there appears to exist a complex signalling machinery tying glial cells to the informational activities of neurons. Some of the functions of these links have also been hinted at. Astrocytes listen into neural activity and step up the local blood flow when things get busy. This is no surprise. But through their control over glutamate recycling, astrocytes appear directly to regulate the effectiveness of individual synapses. They also help new synapses to form. The suspicion is that by their slow background signalling, they may even promote connections between distantly active neurons. Oligodendrocytes respond to neural activity by laying down myelin sheathing. But astrocytes also may help physically sculpt pathways by the way they pack around neurons.

Glia may thus not do anything extraordinary, yet could create a living matrix that greatly enriches the information processing activities of the brain. Glia and neurons would combine as elements of a larger system when it came to the development of memory patterns, the modulation of arousal and responsiveness, the fine-tuning of processing paths.

Some neuroscientists are already a little dismissive of this new view of glial cells. Yes, they say, the information processing activities may be embedded much more deeply in the surrounding tissue than previously realised. But nothing has changed in principle. However for neurologists concerned with brain disease, the discovery of glial processing could actually turn out to be quite important.

For many illnesses could be the result of malfunctions of the complex “ecological balance” of the neuronal-glial system. And if it is precision informational signalling among glia that controls various synapse making and pathway sculpting responses, as well as all the expected inflammatory and homeostatic responses, then perhaps a better understanding of glia will provide many new targets for therapeutic intervention. From epilepsy to schizophrenia, it could be the regulation of slow background processes rather than fast foreground processes which holds the key. So while glial cells are always bound to take second billing to the mighty neuron, it seems more than likely we have to accept that the complex brain just got a lot more complex.

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