As I said in my last blog post, it’s only been fairly recently that we’ve begun to recognize glial cells as being important for anything other than insulation and scaffolding. We now know that glia are important for many aspects of normal brain growth and development, and actively participate in the development of normal synaptic connections between neurons. How did we discover that our “brain glue” is actually something more? What changed?
Almost 20 years ago, a very important scientific paper was published in the journal Science. At that moment in history, President Bill Clinton had just begun his second term in office, NASA’s Pathfinder probe landed on Mars, and the iPhone was just a glimmer in Steve Job’s eye. Written by Frank Pfrieger and Ben (formerly Barbara) Barres in 1997, the paper titled “Synaptic Efficacy Enhanced by Glial Cells In Vitro” (1) changed the way we looked at astrocytes forever.
Scientists had previously discovered that glial cells were important for guiding the growth of neurons, and we knew that many synapses had an astrocytic process wrapped around them, but we were still trying to understand what, exactly, those astrocytes were doing. Drs. Pfrieger and Barres were able to isolate a particular type of neuron from the eyes of rats called retinal ganglion cells, or RGCs. RGCs are the cells responsible for transmitting the signals from the back of your eye to your brain. Pfrieger and Barres discovered a way to grow these cells in a dish using solutions (or “media”) that kept the cells alive without having to add serum. Serum is very useful for providing nutrients to help cells survive and grow, but it contains huge amounts of protein and its protein content is ill-defined, so being able to grow neurons without serum can provide valuable insight into the proteins created by the neurons themselves.
Once they determined how to grow the RGCs in serum-free media, they looked at the differences between RGCs grown by themselves and RGCs grown in a dish with astrocytes. Even though the RGCs could survive without serum, after 5 days, the researchers saw that only around 50% of those cells became electrically active, indicating the ability to send and receive signals from other neurons. In contrast, when RGCs were grown with glia (mostly astrocytes), 90% of those cells showed electrical activity within 5 days. Additionally, when glia were present, the RGCs sent signals more frequently, and the signals were stronger (see Figure 1). This was true even when the scientists grew the glia separately from the neurons, took the solution from the glia cell cultures, and added it to the neurons – meaning that contact between the astrocytes and the neurons wasn’t necessary for this effect. When they examined the RGCs under a microscope, Pfrieger and Barres found that the RGCs that had been grown with glia had a few more synapses with their neighbors than the RGCs without glia, but not enough to account for the dramatic difference in the strength of the signals. By manually manipulating the signals of the RGCs using electrodes, the researchers were able to determine that it’s not so much that the glia help create more synapses, but rather that they appear to create more efficient synapses, allowing better transmission.
Figure 1: Electrical activity in RGCs grown with (right) and without (left) glia. (A) RGCs grown with and without glia look normal and grow at similar densities. (B) RGCs grown with glia show more spontaneous electrical activity than RGCs grown without.
This study threw open a door into an entire field of research, searching to understand how these glial cells encourage neurons to become electrically active, and what exactly the glia doing to increase the efficiency of the synapses. We’ve uncovered some of the answers to these questions, and I’ll write more about it in later posts. This paper, and others like it, set the stage for my own research into the roles of astrocytes in neurodevelopmental disorders. I think it’s every scientist’s dream to write a paper like this one; one that will change the way we think about the world around us, and inform our research for generations to come.
1) Pfrieger, F. W., & Barres, B. A. (1997). Synaptic efficacy enhanced by glial cells in vitro. Science (New York, N.Y.), 277(5332), 1684–1687. doi:10.1126/science.277.5332.1684