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.