The star (fish) shaped astrocyte cell….Credit: Neurorocker

If you’ve had any exposure to how the brain and nervous system works, you probably know about synapses – the juncture where the end of one neuron almost meets the beginning of another neuron. The synapse is two neurons and the gap between them, the point where either chemical neurotransmitters or gap junctions for electrical current carry a nerve signal from one neuron to another. I’m simplifying here in order to get at something that significantly complicates the notion of a synapse. The traditional picture of a synapse tends to obscure the fact that the ‘gap’ (synaptic cleft) between neurons isn’t self contained – it’s part of something outside the neurons. And what is that ‘something’ outside the neurons? Again, traditionally, this has been pictured as the realm of glia, the ‘other’ cells of the brain and nervous system. There are seven kinds of glia and they’ve been considered for a long time to be mainly structural (holding the neurons in place) or supportive (providing nutrients and other housekeeping activity for neurons). In general, the various glia were considered not very interesting compared to the neurons and certainly were not important to the signaling operation of the nervous system. That evaluation is changing and may profoundly affect how we believe the nervous system works.

It’s been known for some time that there are roughly as many glia cells in the brain as there are neurons. Few thought this was significant, although in general, where there is a lot of some material, Nature tends to put it to multiple uses. It was roughly during the 1990’s that researchers began to discover other functions for glia, the most significant was arguably that instead having a passive role in neurotransmission, some forms of glia – astrocytes in particular – have an intimate relationship with neurons in the role of modulating neurotransmission. One of the leaders in these discoveries is Miaken Nedergaard, professor of neurosurgery at the University of Rochester Medical Center (New York, USA). Her pioneering work demonstrated that astrocytes participate in communication with neurons, albeit in a passive role.

The basic idea for astrocytes’ role in the synapse is to regulate the concentration of potassium ions in the synaptic cleft – translated: A signal travelling from one neuron to the other across a synapse may use chemical ions (electrons), including those of potassium and calcium, to transfer the signal. When this happens, astrocytes perform the function of withdrawing ions (potassium) so that the signal will stop, in preparation for the next signal. It was originally assumed that the stopping was controlled by the neurons. The Nedergaard team’s newest research indicates that astrocytes can actively (that is, on their own) stop the signal by withdrawing ions. In a recent paper to be published by Nature Signaling [ April 2012, paywalled, ] the indication is that astrocytes in some way orchestrate the synaptic firing of neurons so that ‘noise’ (random or unwanted neuron activity) is minimized. Neuroscientists call this ‘maintaining synaptic fidelity’ (something like a noise filter on a hi-fi system).

How astrocytes do this ‘orchestration’ and how this all fits together in terms of functioning synapses – to say nothing of how all this fits with general brain and nervous system activity – remains to be seen. As Nedergaard puts it, “Astrocytes are integral to the most sophisticated brain processes.” Indeed, if her team’s findings are corroborated, it implies that the functioning of synapses is more complicated than was already thought. It adds to the notion that there is a ‘third partner’ in the operation of synapses, the astrocytes. What that brings to the party, and why, leaves open questions of potentially high impact. Neuroscientists have already coined a term for this model of neuron activity back around 2006: the tripartite synapse, consisting of the presynapse (axon neuron), postsynapse (dendritic neuron) and glia (astrocytes). Since then, research such as Nedergaard’s continues to show more involvement by astrocytes in modulating how synapses work.

One of the biggest unknowns in neuroscience, especially for the working of the human brain, is how the all-important connections (the synapses) in the neural system (the network of neurons) are organized and cooperate. It appears that the formerly ignored glia may be part of the answer, but the answer, whatever it is, will be yet more complicated. There may be a reason why two of the most complicated intelligences on the planet – humans and elephants – also have the greatest percentage of glia in the brain.