Do the billions of non-neuronal cells in the brain send messages of their own?
Halfway through a satellite meeting at the Federation of European Neurosciences conference in Amsterdam in July, researcher Ken McCarthy takes the stage to give his presentation. He sports a black shirt and jeans, and his strong cheekbones, shock of white hair and tanned skin give him the look of a film star. But he doesn't have the confidence to match. I find this a little bit daunting, he says, as he organizes his slides.
McCarthy, a geneticist at the University of North Carolina School of Medicine in Chapel Hill, is about to fan the flames of a debate about whether glia, the largest contingent of non-neuronal cells in the brain, are important in transmitting electrical messages. For many years, neurons were thought to be alone in executing this task, and glia were consigned to a supporting role regulating a neuron's environment, helping it to grow, and even providing physical scaffolding (glia is Greek for 'glue').
In the past couple of decades, however, this picture has been changing. Some glia, known as astrocytes, have thousands of bushy tendrils that nestle close to the active junctions between neurons the synapses (see'Neural threesome'). Here they seem to listen in on neuronal activity and, in turn, to influence it. Studies show that chemical transmitters released by neurons cause an increase in the levels of calcium inside astrocytes, spurring them to release transmitters of their own. These can enhance or mute the signalling between neurons, or influence the strength of their connections over time. Moreover, astrocytes activated at one synapse might communicate with other synapses and astrocytes with which they make contact.
The consequences of this 'gliotransmission' could be profound. The human brain contains roughly equal numbers of glia and neurons (about 85 billion of each), and any given astrocyte can make as many as 30,000 connections with cells around it. If glia are involved in signalling, processing in the brain turns out to be an order of magnitude more complex than previously expected, says Andrea Volterra, who studies astrocytes at the University of Lausanne in Switzerland. Neuroscientists, who have long focused on the neuron, he says, would have to revise everything. In the past year or so, several papers have highlighted the urgency of this revision.
But the research that McCarthy is about to discuss could put a stop to the enthusiasm. I'm presenting work from genetic studies that fly in the face of gliotransmission, he begins. Most studies so far have investigated astrocytes cultured in dishes, and bombarded them with calcium to elicit an effect. It has long been suggested, however, that these methods aren't specific enough to astrocytes, and might be affecting neurons as well. What is needed is a way to target astrocytes alone. So McCarthy has developed genetically engineered mice in which astrocytes can't signal normally. The mutations seem to have no effect on neuronal transmission in the brain.
His group's finding could come as a relief to some. Given the enormous neural complexity that gliotransmission would imply, people don't want astrocytes to be involved, says Phil Haydon, a neuroscientist who studies glia at Tufts University in Boston, Massachusetts. But many, including most at the Amsterdam meeting, have built their careers on gliotransmission. In addition to their effects on the day-to-day functioning of the central nervous system, glia have opened new avenues of research into sleep, as well as psychiatric and neurological disease. Now, researchers are being forced to prove McCarthy wrong, or re-evaluate the fundamental precepts upon which the field was built. David Attwell, a neuroscientist at University College London, says that emotions in the community are running high. If someone comes along and says that everything you've done is wrong, it's like you've wasted your life, he says. It's become quite a polarized field, just in the last year or two.