By Dillon Lim - Medicine Student @ Brasenose College, Oxford
Glial cells are non-neuronal cells present in the nervous system, once thought to be no more than ‘glue’ – cells that served a purely structural function. The fact that the glia:neuron ratio is probably around 1:1 pushed neuroscientists to re-evaluate the role that they play – you don’t usually use glue in a 1:1 ratio with your substrate!
There are three types of glial cells in the CNS: astrocytes, oligodendrocytes and microglia. In the PNS, astrocytes are replaced by satellite glial cells and oligodendrocytes by Schwann cells – for simplicity, we will just examine the functions of the CNS glia, since the PNS equivalents perform largely similar functions.
Astrocytes account for roughly 60% of central glial cells and mediate diverse functions. They extend processes to neuronal synapses, forming a “tripartite” connection. This connection puts the astrocytes in a position to be able to monitor transmission at synapses, and since they can be plugged into dozens of synapses at a time, potentially compare the relative neuronal activity at different synapses. Astrocytes also are often tightly associated with each other, sometimes forming a continuous network of cells with direct connections between cytoplasm of adjacent cells (a syncytium). This allows them to share chemical signals with each other. Given these physical relationships, astrocytes are well-placed to send neuromodulatory signals, affecting synapses from the timescale of minutes to days and longer.
Typically, when we talk about neurotransmitters at synapses at a Sixth Form level, we talk about their action on postsynaptic neurons, followed by their inactivation or transport back into presynaptic neurons. It is clear, however, that glia have an important role to play in the recycling of neurotransmitter, and actually respond to neurotransmitters themselves. One of the interesting ways this is studied is with the use of Ca2+-sensitive dyes, since many intracellular signals involve the release of Ca2+ within cells. These dyes fluoresce when binding Ca2+, so can be used to visualised the spread of signals through an astrocytic network after activity at a tripartite synapse.
Oligodendrocytes contribute to the myelin sheath of many CNS neurons. A single oligodendrocyte in the periphery provides myelination for 10s of cells (whereas Schwann cells in the periphery are less ambitious, focusing on just one neuron). Myelination increases the resistance across the neuronal membrane, which reduces the leak of current out of the neuron and thus the speed of an action potential. As well as this important function, oligodendrocytes are also involved in some signalling. BDNF is an important protein that promotes growth and differentiation of neurons and has important functions in learning and memory. When we prevent oligodendrocytes from producing BDNF (but allow the rest of the brain to continue normal production), we see presynaptic neurons have noticeably smaller neurotransmitter stores. The relative importance of this (and the other signalling oligodendrocytes participate in) is a lot less well understood, but there’s definitely something going on!
Finally, microglia are similar to macrophages in other peripheral tissues, and are able to recognise signals of damage and infection to trigger inflammatory responses. In the brain they are also important in phagocytosis of dying cells, particularly in the pruning of synapses as old or unrequired connections are lost.
Further reading:
How many glial cells are there in the brain? https://neuroscientificallychallenged.com/posts/how-many-glial-cells-in-the-brain
The Search for True Numbers of Neurons and Glial Cells in the Human Brain: A Review of 150 Years of Cell Counting. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063692/ (advanced; Article 1 is essentially a simple summary of this article).
Glial Cells. https://www.ncbi.nlm.nih.gov/books/NBK441945/
Glial cells in (patho)physiology. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1471-4159.2012.07664.x (advanced)
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