The Little Known Cells That Are As Important As Neurons For Cognition

Astrocyte neuroglial cells in the brain. Source: Getty Images.

When most people think about the brain they think about a huge interconnected network of neurons. Neurons are often called ‘brain cells’, and the two are used interchangeably. Neurons are, of course, critical cells in the makeup of the brain and play key roles in everything the brain is able to do. But it’s incorrect to think of neurons as the only cells in the brain. Or even the most important. In fact, neurons are actually only half the story. If you only considered neurons you’d be missing half the brain — quite literally.

Roughly speaking, there are 85 billion neurons in a typical adult brain. But there are also another 86 billion cells that are not neurons. The most important class of non-neuronal cells are neuroglial cells. And without them, you simply wouldn’t be able to function. In fact, you wouldn’t be you at all. There are three major types of glial cells in the brain: oligodendrocytes, microglia, and astrocytes.

Oligodendrocytes speed up electrical signals in some neurons. When neurons need to send electrical impulses over long distances, oligogendrocytes send out finger-like projections that wrap around parts of the axon, or cable, of the neuron over which these impulses travel. This lets the electrical impulses jump over the axon, thereby speeding up how fast they travel. It’s sort of like skipping instead of walking. In neurological disorders like multiple sclerosis, the body attacks certain proteins in oligodendrocytes that strips away the insulating layer they form along axons, resulting in slower impulses. If left untreated, it can lead to serious motor and functional deficits.

Microglia act as the immune cells of the brain and spinal cord, because the normal immune cells and antibodies in your blood don’t have access to the isolated chemical environment of the central nervous system.

But the most mysterious and important — from the perspective of how the brain learns and processes information — are astrocytes. All together, there are about as many glial cells in your brain as there are neurons. And about 20–40% of all glial cells are astrocytes. Without them, neurons would not be able to function properly. They perform critical house-keeping functions to support a chemical environment that allows neurons to survive. This is what neuroscientists refer to as homeostasis.

But beyond their homeostatic roles, astrocytes are also likely participating and modulating how the brain processes information and achieves cognitive functions.

Supporting neurons — Astrocytes and homeostasis

The 1858 the German pathologist Rudolf Virchow first described neuroglia as a “substance… which lies between the proper nervous parts, holds them together and gives the whole its form in a greater or lesser degree”. The term ‘glia’ has the same origin as the word ‘glue’, since it was initially thought that neuroglia were just there to bind — or hold — neurons together.

It was only later that scientists realized that astrocytes provide homeostatic support for neurons. Neurons are electrically excitable cells — they communicate between each other by passing signals and messages encoded as electrical impulses called action potentials. As such, they are susceptible to becoming overly electrically excited, which if left unchecked can affect their function, and even kill them. Neurons communicate via chemical signaling, and there are many different types of molecules (e.g. neurotransmitters) and charged chemical species (e.g. ions) that participate in creating and propagating action potentials and the messages they carry.

Astrocytes form a network onto themselves that is physically separate from the network formed by neurons. In order to maintain a homeostatic environment, astrocytes ‘mop up’ excess chemicals in the environment. They literally take chemicals like extra neurotransmitters and ions into the interior of the cells through various pumps and channels from the environment they — and neurons — live in.

Once they’re inside astrocytes, the cells shuttle the chemicals internally from astrocyte to astrocyte through their network so they can dump them into the blood stream for disposal. Astrocytes at edge of the network have processes called endfeet that come into close contact with blood vessels. ‘Waste’ chemicals are effectively dumped into the blood stream and whisked away.

In addition to taking waste chemicals away from the brain, astrocytes also bring ‘food’ to neurons. In the reverse direction, astrocytes shuttle glucose and related energy byproducts from the blood stream to areas of high neuronal activity, where neurons at work need energy the most.

The ‘endfeet’ of astrocytes make contact with blood vessels. This allows the cells to shuttle away ‘waste’ chemicals from neurons, but also bring glucose to active neurons — all through the cell network they form. Source: Getty Images.

Astrocytes are likely critical to cognition and memory

In the early 1990’s neuroscientists recognized that the neurotransmitter glutamate, one of the most important signaling molecules in the brain responsible for how neurons ‘talk’ to each other, was also capable of activating astrocytes and inducing long range communication within astrocyte networks. The scientists realized that astrocytes have the ability to eavesdrop and listen in as neurons talk to each other. But unlike neurons though, when astrocytes are activated by neurotransmitters like glutamate, they don’t communicate with each other via electrical impulses, but rather by using calcium and other forms of chemical signaling.

In addition to detecting neurotransmitter signaling and communications between neurons, they also have the ability to release neurotransmitters presumably capable of modulating neuronal activity. In effect, they have the ability shape information processing in the brain. When neurotransmitters are released by astrocytes rather than neurons they are referred to as gliotransmitters. But they are chemically the exact same thing.

The intimate association between neurons and astrocytes takes place at the tripartite synapse, or three part synapse. A synapse is the connection point where two neurons meet and pass signals between one another. When a neuron becomes electrically excited a wave of electrical activity propagates down its axon until it reaches the synapse, which in turn triggers the release of neurotransmitters that act as a chemical message. In a tripartite synapse, a part of the astrocyte wraps around the neuronal synapse in order to listen in and participate in the signaling process.

A single astrocyte can extend multiple tentacle-like arms to different synapses, so it can participate in many tripartite synapses. One implication of this fact is that an astrocyte may be able to functionally connect pairs of neurons that normally would not be connected. It’s possible that synaptic signaling at one tripartite synapse leads to the astrocyte affecting a different synapse it’s connected to. In effect, an astrocyte can ‘short circuit’ the neuronal network.

There is accumulating data that suggests astrocytes have a number of important roles in physiological processes that affect cognition. For example, they modify synaptic plasticity — the ‘strength’ of the connections between neurons. And they play an important role in memory consolidation and how vigilance and arousal affect what we remember and how.

Yet, even though neuroscientists know quite a bit about the molecular biology, biophysics, and chemical makeup of astrocytes, they still have no real idea how astrocytes ultimately influence and modulate neuronal signaling and information processing. There are a number of ideas and hypothesis, but there is a lack of anything close to a coherent mechanistic understanding of their computational role in the brain. This is one arguably of the most exciting areas of neuroscience at the very boundary of our knowledge about the brain.

We literally have a second network in our brains beyond the network of neurons that plays a critical role not just in maintaining the health of the brain, but that also affects learning and information processing in ways neuroscientists do not yet understand. And scientists have even less understanding of what roles astrocytes might contribute to in complex neurodevelopmental and neuropsychiatric disorders such as autism or schizophrenia.

Will astrocytes be important for further advances in machine learning and AI?

Beyond neuroscience and the biological brain, incorporating astrocytic-like elements into artificial neural networks might have implications for future machine learning and artificial intelligence.

Engineering astrocytic-like elements into artificial neural networks might have implications in next-generation algorithms. In fact, there have been some early attempts at building neuronal-astrocyte-like artificial neural networks that suggest an improved performance on classification tasks. In general, machine learning and artificial intelligence arguably may have a lot to learn from the biological brain.

This article was originally published on Forbes.com. You can check out this and other pieces written by the author on Forbes here.

Professor of Bioengineering and Neurosciences, University of California San Diego