Are neurons all they’re cracked up to be?

For decades, we have believed the neuron to be the king of all cells.

Neurons are grown at a rate of 250,000 cells per minute in utero, culminating in a fully grown brain with 100 billion neurons, and over 100 trillion neuronal connections. This is more than all the stars in the universe, all of them working together to create you.

Triggered by neurotransmitters, neurons send electrical signals to one another from the cell body (the head of the cell) down the axon (the tail of the cell) and onto the next neuron via dendrites (tree-like structures which receive the electrical signal from neighbouring cells). This change in electrical signal is known as the action potential.

This basic explanation of how neurons communicate is often used when neuroscientists explain any neurological phenomenon. From memory to balance, everybody talks about neuronal communication.

And yet, a king cannot rule without the support of loyal staff and subjects. There is a little-known cell supporting the neuron, and as our understanding grows, it is becoming apparent that they are vital to maintain a healthy, functional brain.

Glial cells

Glial cells, the smaller cousins of the neuron, are actually abundant in the brain and estimates suppose a ratio of 1:1 between glial cells and neurons (previous estimates proposed a ratio of 10:1 in favour of glial cells, but there is actually no evidence to support this).

For such a plentiful cell, you may be wondering why they have been hiding in the background of neuroscientific research for so long. First discovered in the 19th century, glial cells were thought to act solely as “nerve glue” (“glia” literally means “glue” in Ancient Greek). Unlike their fancier counterparts, glial cells cannot produce an action potential of their own, and so it was believed they could not play an important role in ‘brain communication’.

Only in recent years have scientists begun to wonder if glial cells do more than ‘hold the brain together’. There is a very long way to go before we understand the function of these cells, but it is clear they are not quite as mundane as once believed.

What are glial cells?

There are four types of glial cell which have different origins and functions:

• microglia
• astrocytes
• oligodendrocytes
• oligodendrocyte progenitors, NG2-glia (glial stem cells)

The majority of glial cells are derived from ectodermal tissue, one of the three germ layers of tissue present within the early development of an embryo. Microglia, however, come from yolk-sac progenitors that seed the development of the brain itself.

Microglia are primarily involved with repairing damage following neurological damage, though this is not necessarily limited to traumatic brain injuries or illnesses; they are also involved with the regular clean-up following apoptosis (programmed cell death). Astrocytes are star-shaped cells (hence “astro”) which ensure the chemical environment is optimal for neuronal signalling. Oligodendrocytes carry out the process of myelination, a protein and lipid compound which supports and insulates axons. Without myelin, neuronal communication is very slow and can cause a number of conditions including multiple sclerosis. NG2-glia are precursors to oligodendrocytes, though evidence suggests they may also be able to differentiate into astrocytes and neurons as well.

New Research

It is now clear that glial cells support neurons to function as effectively as possible, but a new study from the University of California has found that they may actually actively influence the way neurons behave.

Professor Iryna Ethell and her team have found that the overproduction of a protein called ephrin-B1, in the astrocytes of mice, is linked with a reduced ability to retain memory.

They examined the differences between male mice brains which exhibited overexpression of ephrin-B1 and compared them to ephrin-B1 knockout mice brains (within which ephrin-B1 had been inactivated).

They found that those mice who showed overexpression were unable to remember a behaviour they had just learned, and in cell cultures they saw astrocytes pruning the synapses of neighbouring neurons. This indicates that astrocytes which express too much ephrin-B1 can attack neurons and remove synapses, which limits the communication between neurons and reduces learning ability.

Conversely, down-regulation of ephrin-B1 results in a greater number of synapses and better learning.

There is an important balance to be found between the right number of synapses; too few and no neural communication can take place, but too many and no new connections can be made.

“You don’t want to remember everything…It’s all about maintaining a balance: being able to learn but also to forget” Amanda Q Nguyen, co-first author.

This overproduction of ephrin-B1 is not necessarily a problem as synaptic pruning is important, but excessive removal may lead to neurodegeneration.

The team at the University of California plan to follow up this study with an investigation as to why this pruning is only seen from some astrocytes, but not others.

The research has been published in the Journal of Neuroscience.