After 180 years, new clues reveal how general anesthesia works in the brain


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More than 350 million operations are performed worldwide every year. For most of us, it is likely that at some point in our lives we will need to undergo a procedure that requires general anesthesia.

Although it is one of the safest medical practices, we still do not have a complete and thorough understanding of exactly how anesthetics work in the brain.

In fact, it has largely remained a mystery since general anesthesia was introduced into medicine over 180 years ago.

A study published in the Journal of Neuroscience provides new clues about the complexity of the process. General anesthetic drugs only seem to affect specific parts of the brain that help keep us alert and awake.

Brain cells reaching equilibrium

In a study with fruit flies, we found a possible way that anesthetics can interact with specific types of neurons (brain cells), and it all has to do with proteins. Your brain has about 86 billion neurons and they are not all the same. It is these differences that make general anesthesia effective.

To be clear, we are not completely in the dark about how anesthetics affect us. We know why general anesthesia can make us lose consciousness so quickly, thanks to a groundbreaking discovery in 1994.

But to better understand the fine details, we must first look at the tiny differences between the cells in our brains.

Broadly speaking, there are two main categories of neurons in the brain.

The first are what we call ‘excitatory’ neurons, which generally keep us alert and awake. The second are the ‘inhibitory’ neurons; their job is to regulate and control the excitatory neurons.

In our daily lives, excitatory and inhibitory neurons constantly work together and keep each other in balance.

When we fall asleep, there are inhibitory neurons in the brain that ‘silence’ the excitatory neurons that keep us awake. This happens gradually over time, so you may feel more and more tired as the day progresses.

General anesthetics accelerate this process by directly silencing these excitatory neurons, without any action from the inhibitory neurons. This is why your anesthesiologist will tell you that they will “put you to sleep” for the procedure: it is essentially the same process.

A special kind of sleep

Although we know why anesthesia puts us to sleep, the question arises: “Why do we stay asleep during surgery?”. If you went to bed tonight, fell asleep and someone tried to operate on you, you woke up with quite a jolt.

To date, there is no strong consensus in the field as to why general anesthesia causes people to remain unconscious during surgery.

Over the past few decades, researchers have proposed several possible explanations, but they all seem to point to one main cause. Neurons stop talking to each other when exposed to general anesthetics.

While the idea of ​​’cells talking to each other’ may sound a bit strange, it is a fundamental concept in neuroscience. Without this communication, our brains would not be able to function at all. And it ensures that the brain knows what is happening throughout the body.

What have we discovered?

Our new study shows that general anesthetics appear to prevent the communication of excitatory neurons, but not inhibitory neurons. This concept is not new, but we have found compelling evidence for it Why only excitatory neurons are affected.

In order for neurons to communicate, proteins must become involved. One of the jobs of these proteins is to cause neurons to release molecules called neurotransmitters. These chemical messengers carry signals from one neuron to another: for example, dopamine, adrenaline and serotonin are all neurotransmitters.

We found that general anesthetics reduce the ability of these proteins to release neurotransmitters, but only in excitatory neurons. To test this, we used Drosophila melanogaster fruit flies and super-resolution microscopy to directly see what effects a general anesthetic had on these proteins on a molecular scale.

Part of what sets excitatory and inhibitory neurons apart is that they express different types of the same protein. This is like having two cars of the same make and model, but one is green and has a sports package, while the other is just standard and red. They both do the same thing, but one is a little different.

The release of neurotransmitters is a complex process involving many different proteins. If one piece of the puzzle isn’t quite right, general anesthesia can’t do their job.

As a next research step, we will have to figure out which piece of the puzzle is different, to understand why general anesthetics only block excitatory communication.

Ultimately, our results indicate that the drugs used in general anesthetics cause massive global inhibition in the brain. By silencing irritability in two ways, these drugs put us to sleep and keep us that way.

Provided by The Conversation

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