How anaesthetic drugs work in the brain has largely remained a mystery since it was introduced into medicine over 180 years ago.
| Photo Credit: The Hindu

Over 350 million surgeries are performed globally each year. For most of us, it’s likely at some point in our lives we’ll have to undergo a procedure that needs general anaesthesia.

Even though it is one of the safest medical practices, we still don’t have a complete, thorough understanding of precisely how anaesthetic drugs work in the brain.

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

Our study published in The Journal of Neuroscience today provides new clues on the intricacies of the process. General anaesthetic drugs seem to only affect specific parts of the brain responsible for keeping us alert and awake.

Brain cells striking a balance

In a study using fruit flies, we found a potential way that allows anaesthetic drugs to interact with specific types of neurons (brain cells), and it’s all to do with proteins. Your brain has around 86 billion neurons and not all of them are the same – it’s these differences that allow general anaesthesia to be effective.

To be clear, we’re not completely in the dark on how anaesthetic drugs affect us. We know why general anaesthetics are able to make us lose consciousness so quickly, thanks to a landmark discovery made in 1994.

But to better understand the fine details, we first have to look to the minute 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, generally responsible for keeping us alert and awake. The second are “inhibitory” neurons – their job is to regulate and control the excitatory ones.

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In our day-to-day lives, excitatory and inhibitory neurons are constantly working and balancing one another.

When we fall asleep, there are inhibitory neurons in the brain that “silence” the excitatory ones keeping us awake. This happens gradually over time, which is why you may feel progressively more tired through the day.

General anaesthetics speed up this process by directly silencing these excitatory neurons without any action from the inhibitory ones. This is why your anaesthetist will tell you that they’ll “put you to sleep” for the procedure: it’s essentially the same process.

A special kind of sleep

While we know why anaesthetics put us to sleep, the question then becomes: “why do we stay asleep during surgery?”. If you went to bed tonight, fell asleep and somebody tried to do surgery on you, you’d wake up with quite a shock.

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

Over the last couple of decades, researchers have proposed several potential explanations, but they all seem to point to one root cause. Neurons stop talking to each other when exposed to general anaesthetics.

While the idea of “cells talking to each other” may sound a little strange, it’s a fundamental concept in neuroscience. Without this communication, our brains wouldn’t be able to function at all. And it allows the brain to know what’s happening throughout the body.

What did we discover?

Our new study shows that general anaesthetics appear to stop excitatory neurons from communicating, but not inhibitory ones. This concept isn’t new, but we found some compelling evidence as to why only excitatory neurons are affected.

For neurons to communicate, proteins have to get involved. One of the jobs these proteins have is to get neurons to release molecules called neurotransmitters. These chemical messengers are what gets signals across from one neuron to another: dopamine, adrenaline and serotonin are all neurotransmitters, for example.

We found that general anaesthetics impair 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 anaesthetic was having on these proteins at a molecular scale.

Part of what makes excitatory and inhibitory neurons different from each other is that they express different types of the same protein. This is kind of 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’s just a little bit different.

Neurotransmitter release is a complex process involving lots of different proteins. If one piece of the puzzle isn’t exactly right, then general anaesthetics won’t be able to do their job.

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

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

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Heart in your throat. Butterflies in your stomach. Bad gut feeling. These are all phrases many people use to describe fear and anxiety. You have likely felt anxiety inside your chest or stomach, and your brain usually doesn’t hurt when you’re scared. Many cultures tie cowardice and bravery more to the heart or the guts than to the brain.

But science has traditionally seen the brain as the birthplace and processing site of fear and anxiety. Then why and how do you feel these emotions in other parts of your body?

I am a psychiatrist and neuroscientist who researches and treats fear and anxiety. In my book Afraid, I explain how fear works in the brain and the body and what too much anxiety does to the body. Research confirms that while emotions do originate in your brain, it’s your body that carries out the orders.

Also Read | Where the mind is without fear: What is anxiety and how can we beat it? 

Fear and the brain

While your brain evolved to save you from a falling rock or speeding predator, the anxieties of modern life are often a lot more abstract. Fifty-thousand years ago, being rejected by your tribe could mean death, but not doing a great job on a public speech at school or at work doesn’t have the same consequences. Your brain, however, might not know the difference.

There are a few key areas of the brain that are heavily involved in processing fear.

When you perceive something as dangerous, whether it’s a gun pointed at you or a group of people looking unhappily at you, these sensory inputs are first relayed to the amygdala. This small, almond-shaped area of the brain located near your ears detects salience, or the emotional relevance of a situation and how to react to it. When you see something, it determines whether you should eat it, attack it, run away from it or have sex with it.

Threat detection is a vital part of this process, and it has to be fast. Early humans did not have much time to think when a lion was lunging toward them. They had to act quickly. For this reason, the amygdala evolved to bypass brain areas involved in logical thinking and can directly engage physical responses. For example, seeing an angry face on a computer screen can immediately trigger a detectable response from the amygdala without the viewer even being aware of this reaction.

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The hippocampus is near and tightly connected to the amygdala. It’s involved in memorizing what is safe and what is dangerous, especially in relation to the environment – it puts fear in context. For example, seeing an angry lion in the zoo and in the Sahara both trigger a fear response in the amygdala. But the hippocampus steps in and blocks this response when you’re at the zoo because you aren’t in danger.

The prefrontal cortex, located above your eyes, is mostly involved in the cognitive and social aspects of fear processing. For example, you might be scared of a snake until you read a sign that the snake is nonpoisonous or the owner tells you it’s their friendly pet.

Although the prefrontal cortex is usually seen as the part of the brain that regulates emotions, it can also teach you fear based on your social environment. For example, you might feel neutral about a meeting with your boss but immediately feel nervous when a colleague tells you about rumors of layoffs. Many prejudices like racism are rooted in learning fear through tribalism.

Also Read | Mental health awareness month: how to cope in the age of anxiety  

Fear and the rest of the body

If your brain decides that a fear response is justified in a particular situation, it activates a cascade of neuronal and hormonal pathways to prepare you for immediate action. Some of the fight-or-flight response – like heightened attention and threat detection – takes place in the brain. But the body is where most of the action happens.

Several pathways prepare different body systems for intense physical action. The motor cortex of the brain sends rapid signals to your muscles to prepare them for quick and forceful movements. These include muscles in the chest and stomach that help protect vital organs in those areas. That might contribute to a feeling of tightness in your chest and stomach in stressful conditions.

The sympathetic nervous system is the gas pedal that speeds up the systems involved in fight or flight. Sympathetic neurons are spread throughout the body and are especially dense in places like the heart, lungs and intestines. These neurons trigger the adrenal gland to release hormones like adrenaline that travel through the blood to reach those organs and increase the rate at which they undergo the fear response.

Also Read | How anxiety can look different in children

To assure sufficient blood supply to your muscles when they’re in high demand, signals from the sympathetic nervous system increase the rate your heart beats and the force with which it contracts. You feel both increased heart rate and contraction force in your chest, which is why you may connect the feeling of intense emotions to your heart.

In your lungs, signals from the sympathetic nervous system dilate airways and often increase your breathing rate and depth. Sometimes this results in a feeling of shortness of breath.

As digestion is the last priority during a fight-or-flight situation, sympathetic activation slows down your gut and reduces blood flow to your stomach to save oxygen and nutrients for more vital organs like the heart and the brain. These changes to your gastrointestinal system can be perceived as the discomfort linked to fear and anxiety.

It all goes back to the brain

All bodily sensations, including those visceral feelings from your chest and stomach, are relayed back to the brain through the pathways via the spinal cord. Your already anxious and highly alert brain then processes these signals at both conscious and unconscious levels.

The insula is a part of the brain specifically involved in conscious awareness of your emotions, pain and bodily sensations. The prefrontal cortex also engages in self-awareness, especially by labeling and naming these physical sensations, like feeling tightness or pain in your stomach, and attributing cognitive value to them, like “this is fine and will go away” or “this is terrible and I am dying.” These physical sensations can sometimes create a loop of increasing anxiety as they make the brain feel more scared of the situation because of the turmoil it senses in the body.

Although the feelings of fear and anxiety start in your brain, you also feel them in your body because your brain alters your bodily functions. Emotions take place in both your body and your brain, but you become aware of their existence with your brain. As the rapper Eminem recounted in his song “Lose Yourself,” the reason his palms were sweaty, his knees weak and his arms heavy was because his brain was nervous.