Neurotransmitters

What are Neurotransmitters?

Inside the brain, there are approximately 86 billion neurons. All of these neurons form an intricate map of connections and pathways that make up our behaviours, thoughts, memories, movements, speech and so on. The way these neurons form these connections is through what is called a ‘synapse’, the point at which electrical (electrical synapse) or chemical (chemical synapse) signal is transferred from one cell to another. 

Electrical signals are transferred when the two cells involved are physically connected by tiny holes, through which the nerve impulses are transmitted. These types of signals tend to be faster than those of the chemical type. Nevertheless, they also tend to be less flexible than its counterpart. 

Chemical signals, on the other hand, happen when the cells involved do not physically touch. Instead, in between them there is a very narrow gap, in the order of 0.02 micron, that must be bridged by particular molecules. The molecules in charge of making this bridge are the ones called neurotransmitters. 

The first neurotransmitter to be discovered was acetylcholine. The experiment that led to its discovery was revealed in a dream to an Austrian scientist called Otto Lowei in 1921.

How does the chemical synapse work? 

A chemical synapse involves a number of components. First and foremost, it involves a presynaptic neuron, from which the nerve impulse is sent, and a postsynaptic neuron, where the nerve impulse arrives. 

Vesicles containing neurotransmitters can be found at the terminal button of the presynaptic neuron’s axon. When a chemical signal is transferred, the neurotransmitters inside the vesicles are secreted into the synaptic gap by a process called exocytosis. During this process, the vesicles’ membranes fuse with that of the presynaptic button, releasing the neurotransmitters into the gap. 

Across the gap, the just released neurotransmitters bind to membrane receptors on the postsynaptic neuron. These membrane receptors are large proteins that are anchored in the cell membrane of the postsynaptic neuron. Once the neurotransmitters bind to the receptors, they trigger a cascade of events within the cell that will alter its internal behaviour. 

Neurotransmitters that lead to the further propagation of the chemical signal by the receiving cell are called excitatory neurotransmitters. Those that reduce the likelihood of the receiving neuron to propagate the signal are called inhibitory neurotransmitters. 

The binding between the neurotransmitters and the membrane receptors happens in a way that is somewhat similar to a lock and key. For the binding to occur, the lock (receptor) and the key (neurotransmitter) must have perfectly complementing shapes. Also somewhat like it happens with locks and keys, a single key (neurotransmitter) might be able to unlock a number of different locks (receptors). Different locks (receptors) on the other hand might be unlocked by different keys (receptors). 

How many different types of neurotransmitters and receptors are there? 

So far, it is known that over hundreds of different receptors and over sixty different neurotransmitters exist. Molecules considered to be neurotransmitters include amino acids such as glutamate; monoamines, such as serotonin; peptides such as opioid peptides and other molecules such as acetylcholine or soluble gases, such nitrogen monoxide (NO). Molecules such as NO have their own mechanism of action, in which the gas simply diffuses and penetrates the membrane of the receiving neuron. 

Usually, for a molecule to be considered a neurotransmitter it must satisfy a number of different criteria. For instance, it must be produced inside a neuron, it must be found in the neuron’s terminal button and it must also be released into the synaptic gap when an action potential stimulates the cell. Furthermore, the released molecule must produce an effect on the postsynaptic neuron and this same effect must be demonstrated via external experimentation. Another criteria is that, after the signal transmission, the molecule is quickly deactivated. Nitrogen monoxide, which can be considered a neurotransmitter, nevertheless, does not fit all of these criteria, showing there are always some exceptions to the rule. 

What are the main neurotransmitters? 

Some of the best known neurotransmitters are acetylcholine, dopamine, GABA, Glutamate, Norepinephrine (also called noradrenaline) and serotonin. All of these, apart from acetylcholine, belong to the family of amines or amino acids. 

The effects of each of the different neurotransmitters can vary a lot depending on where the receptor for it is located, what type of receptor it is and what are the circumstances for its activation. Below you can have a look at some of these effects. 

Acetylcholine

It seems that, amongst many other roles, acetylcholine plays an important part in learning and memory. It might also play a role in emotions and mood and in wakefulness. The neurons that produce this neurotransmitter are spread all over the brain and the receptors that bind to it are the muscarinic receptors and the nicotinic receptors, the same receptor that binds to nicotine. 

Dopamine

Dopamine is the main neurotransmitter for pleasure or a sense of reward. If something makes you feel good, probably dopamine has a role in it. Despite being responsible for such a pleasant emotion, nevertheless, dopamine has also its own downside. Most of the known addictive substances that exist nowadays affect the dopamine release. So far, it is known that dopamine can bind to 5 different receptors (D1 to D5). Drugs such as cocaine and amphetamines are indirect agonists of dopamine.

GABA

GABA, full name gamma-aminobutyric acid, is the main responsible for the inhibition of nervous activity. The main purpose of this neurotransmitter is to slow down the brain. GABA receptors are split into two types: GABA A receptors and GABA B receptors. Drugs that act as GABA agonists, like alcohol or benzodiazepines, unsurprisingly, are associated with a sedative effect. 

Glutamate

As opposed to GABA, glutamate is the ‘on’ switch of the brain. Its main purpose is that of exciting the neuron that receives it, making it more likely that such neuron will release its own mix of neurotransmitters. There are many different types of glutamate receptors, some of them are NMDA, Kainate and AMPA. Ketamine is a Kainate receptor antagonist, meaning it will produce somehow opposite effects to what glutamate usually does. 

Norepinephrine

Basically, the main role of norepinephrine is to prepare the body for action. Norepinephrine release is at its lowest during sleep and has its highest levels during situations of stress of danger. Norepinephrine binds to the adrenergic receptors alpha-1, alpha-2, beta-1 and beta-3. Amphetamines and methamphetamines interact with norepinephrine receptors. 

Serotonin

Serotonin is probably one of the best known neurotransmitters amongst psychonauts. Its main role within the brain is that of improving the overall state of mood. There are many receptors that are associated with this neurotransmitter, which can be divided into seven families. Due to the variety of different receptors to which serotonin can bind and the downstream effects that serotonin binding can produce, this neurotransmitter may end up having effects on a multitude of different neurotransmitters throughout different parts of the brain. Drugs such as MDMA and LSD interact with serotonin receptors. 

Where can I find more information? 

To learn more about the brain, check out ‘the brain from top to bottom’, to have an overview of all different neurotransmitters check out this list, for a summary of the main neurotransmitters check out this table.