Restraining the Brain: The Role of Microglial Cells in Suppressing Neural Activity

Illustrated by Alexandra Laufer

Even before birth, the human mind is teeming with activity. A single touch, taste or sound can set off a chain reaction in the brain, exciting hundreds of thousands of neurons. These neurons make up networks that are responsible for everything from reaching for a glass of water to picturing a still lake. Filled with experiences like these, our everyday lives constantly rely on neural networks, employing most of the 86 million neurons in our brains [7]. Yet, our thoughts and behaviors are relatively precise—we rarely reach for a glass of water and miss the glass completely. Considering the extensive neural activity required, how are controlled movements of this sort consistently performed without fail? What in our brains is responsible for this precision?

Luckily, scientific research has reached a point where a quick Google search is all it takes to find our answer: microglial cells. By removing damaged neurons and preventing infection, microglial cells (also known as microglia) were thought to be nothing more than the immune cells of the brain [5]. However, recent research by Dr. Katerina Akassoglou and her team revealed the role that microglia play in restraining neural activity. While examining brain tissue under a microscope, they saw the microglial cells repeatedly extended and retracted its processes—the protruding string-like fibers of the cell—to nearby neurons. The researchers discovered, upon closer inspection, that microglia only extend their processes to active neurons; furthermore, the neurons it contacted seemed unable to increase their firing rate [1]. Microglial cells seem to ‘know’ which neurons are at risk of hyperactivity and extend their processes to prevent those neurons from overfiring. In this way, microglia act almost like resistors in a circuit, tempering the brain’s electrical activity to create the necessary precision in behavior and thought.

Without the restraint provided by microglia, every neuron would be at far greater risk of overfiring. Even just one overfiring neuron could overstimulate entire neural networks in the brain, generating repercussions far worse than missing a glass of water. Dr. Akassoglou’s team investigated the repercussions of having no microglial restraint using an experimental group of mice that had been modified to prevent microglial processes from extending. Over time, the researchers witnessed several spontaneous seizures throughout the experimental group [1]. These seizures imply that the microglial cells’ continuous monitoring and suppression in a normal brain to prevent overexcitation was preventing epilepsy. A similar but unrelated study by Vinet et al. found corroborating results and identified a 25 to 70% increase in neurodegeneration across the experimental group mice compared to control group mice [6]. Coupled with their immunological function, microglia appear to serve a vital role in maintaining a stable neural environment. Increasing microglial activity may even have the potential to produce an effective anti-epileptic medication.

Unfortunately, the benefits of elevated microglial activity persist only in the short-term, and eventually the heightened activation results in widespread necrosis (cell death) [2]. Renowned neuroscientists Edith and Patrick McGeer explain that the release of oxygen-free radicals by microglia activated for an extended period is what accounts for this result [4]. Oxygen-free radicals are very reactive unstable molecules capable of breaking down the cellular structure of neurons [3]. The neurodegenerative effect of microglia is understandable considering their function as a restraint: when suppressing neural activity for an extended period, killing the neuron is more energetically than constantly expending energy to suppress it. Additionally, the continual suppression of a neuron could be misinterpreted by a microglial cell as a sign that the neuron is damaged. Such a misinterpretation may trigger the microglial cell’s immune response, justifying the oxygen-free radical release.

Microglial manipulation might still hold some promise in producing future anti-epileptic medication, but to avoid long-term consequences, it must be explored with caution. All this new research says for certain is that microglial cells play an integral role in preserving the network of neurons in our minds. And, in doing so, microglia are indirectly responsible for all of our experiences.

Edited by: Neha Adari
Illustrated by: Alexandra Laufer

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