Neurons communicate between each other chemically across small gaps. what are these gaps called?

Discovery of Neurotransmitters

In 1921, an Austrian scientist named Otto Loewi discovered the first neurotransmitter.

Otto Loewi's Experiment

Neurotransmitter Criteria

Neuroscientists have set up a few guidelines or criteria to prove that a chemical is really a neurotransmitter. Not all of the neurotransmitters that you have heard about may actually meet every one of these criteria.

The chemical must be produced within a neuron.	The chemical must be found within a neuron.
When a neuron is stimulated (depolarized), a neuron must release the chemical.	When a chemical is released, it must act on a post-synaptic receptor and cause a biological effect.
After a chemical is released, it must be inactivated. Inactivation can be through a reuptake mechanism or by an enzyme that stops the action of the chemical.	If the chemical is applied on the post-synaptic membrane, it should have the same effect as when it is released by a neuron.

Neurotransmitter Types

There are many types of chemicals that act as neurotransmitter substances. Below is a list of some of them.

Small Molecule Neurotransmitter Substances

Amino Acids

Neuroactive Peptides - partial list only!

Soluble Gases

Synthesis of Neurotransmitters

Acetylcholine is found in both the central and peripheral nervous systems. Choline is taken up by the neuron. When the enzyme called choline acetyltransferase is present, choline combines with acetyl coenzyme A (CoA) to produce acetylcholine.

Dopamine, norepinephrine and epinephrine are a group of neurotransmitters called "catecholamines". Norepinephrine is also called "noradrenalin" and epinephrine is also called "adrenalin". Each of these neurotransmitters is produced in a step-by-step fashion by a different enzyme.

Transport and Release of Neurotransmitters

Unlike other neurotransmitters, nitric oxide (NO) is not stored in synaptic vesicles. Rather, NO is released soon after it is produced and diffuses out of the neuron. NO then enters another cell where it activates enzymes for the production of "second messengers."

Receptor Binding

Neurotransmitters will bind only to specific receptors on the postsynaptic membrane that recognize them.

Inactivation of Neurotransmitters

The action of neurotransmitters can be stopped by four different mechanisms:

1. Diffusion: the neurotransmitter drifts away, out of the synaptic cleft where it can no longer act on a receptor.	Diffusion
2. Enzymatic degradation (deactivation): a specific enzyme changes the structure of the neurotransmitter so it is not recognized by the receptor. For example, acetylcholinesterase is the enzyme that breaks acetylcholine into choline and acetate.	Enzymatic degradation
3. Glial cells: astrocytes remove neurotransmitters from the synaptic cleft.	Glial Cells Astrocyte Image courtesy of Biodidac
4. Reuptake: the whole neurotransmitter molecule is taken back into the axon terminal that released it. This is a common way the action of norepinephrine, dopamine and serotonin is stopped...these neurotransmitters are removed from the synaptic cleft so they cannot bind to receptors.	Reuptake

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Did you know?

The idea for the famous heart experiment came to Otto Loewi in his sleep. In Loewi's own words: "In the night of Easter Saturday, 1921, I awoke, turned on the light, and jotted down a few notes on a tiny slip of paper. Then I fell asleep again. It occurred to me at six o'clock in the morning that during the night I had written down something most important, but I was unable to decipher the scrawl. That Sunday was the most desperate day in my whole scientific life. During the next night, however, I awoke again, at three o'clock, and I remembered what it was. This time I did not take any risk; I got up immediately, went to the laboratory, made the experiment on the frog's heart, described above, and at five o' clock the chemical transmission of nervous impulse was conclusively proved." --- quoted from Loewi, O., From the Workshop of Discoveries, Lawrence: University of Kansas Press, 1953.

Copyright © 1996-2020, Eric H. Chudler All Rights Reserved.

Imagine that you want to tell your friends something new; you could whisper it into their ears or shout it out loud. This is rather like two forms of communication that occur within your brain. Your brain contains billions of nerve cells, called neurons, which make a very large number of connections with specialized parts of other neurons, called dendrites, to form networks. Neurons have been thought to communicate with each other by passing (“whispering”) chemical signals directly through these connections, but now we know that they also can spread messages more widely (“public announcements”) by releasing chemical signals from other parts of the neuron, including the dendrites themselves. If we understand how and what neurons communicate with each other, we will have a chance to correct disturbances in communication that may result in altered behaviors and brain disorders.

We know that the human brain is the most complex structure. It has approximately 80 billion nerve cells, called neurons. Eighty billion (80,000,000,000)! This is more than 10 times as many neurons as there are people living on Earth. Neurons talk to each other using special chemicals called neurotransmitters. Neurotransmitters are like chemical words, sending “messages” from one neuron to another. There are many different sorts of neurotransmitters: some stimulate neurons, making them more active; others inhibit them, making them less active. Neurons control literally everything you do.

The Neurons are the Building Blocks of Your Brain

Neurons come in many forms, shapes and sizes, but it is helpful to think of a neuron like a tree. A neuron has three main parts, the cell body, an axon, and the dendrites (Figure 1). The tree trunk (cell body) stores genetic information (DNA) in a compartment called the nucleus. The cell body also contains the chemical machinery to produce the neurotransmitters that the neuron uses to communicate with each other.

• Figure 1
• A. Some neurons, like this special kind of neuron called a Purkinje cell, look very similar to trees B. C. Neurotransmitters (key) released from the axon terminals only have to cross a very tiny gap (a synapse) D. to reach their receptors (lock). However, when they are released from dendrites, their receptors can be far away and need to be reached by diffusion. Purkinje cell image courtesy of Marta Jelitai, Hungary.

The tree’s branches (dendrite, the word déndron comes from the Greek language and actually means “tree”) are the parts of a neuron that receive signals. Dendrites were once thought to be like antennae, just receiving signals from other neurons, but, as I explain, they can do more than this.

The tree root (axon) is the structure used by a neuron to connect with and talk to another neuron. An axon carries information similar to a cable that carries electricity. When one neuron wants to share a message with another, it sends an electrical impulse, called an action potential, down its axon until it reaches the axon terminal, at the end of the axon. Think of an axon terminal as an airport terminal. An airport terminal is filled with passengers waiting to depart, whereas an axon terminal is filled with neurotransmitters waiting to travel to the next neuron.

What are the Differences Between Wired and Wireless Transmission?

When the action potential reaches the axon terminal, some of the neurotransmitters in the terminal are dumped into a tiny gap between the terminal and the dendrite of another neuron. This gap is called a synapse—it is so tiny that it is measured in nanometers or billionths of a meter. The neurotransmitter crosses the synapse and binds to a specialized site, called a receptor, on the other side. Each neurotransmitter binds only to its specific receptor, just as a key fits only in a particular lock. Depending on the neurotransmitter, it either stimulates the other neuron or inhibits, making it either more likely or less likely to fire an action potential of its own. All these happens with very high precision and is repeated again and again. Since the signal is passed at very high speed from one neuron to another (up to 100 m/s or 223 mph; faster than the fastest land mammal, the cheetah, which can accelerate to a speed of 29 m/s or 64 mph), this kind of communication between neurons is sometimes called “wired transmission.” The neurotransmitters pass “whispered secrets” directly from one neuron to another; they carry a message that matters only at a particular time and place. One way of thinking about “wired transmission” is to think about a light switch, which switches a particular light bulb on or off.

Some neurotransmitters, especially one kind called neuropeptides, are different. Neuropeptides are released from many parts of a neuron, including the dendrites. Rather than being released into the tiny synapse between an axon terminal and another neuron, they are released into the fluid that fills the spaces between neurons, and they diffuse through the brain to reach receptors that are on distant targets. One way of thinking about diffusion is to consider making your way through a forest (Figure 2). To go from one point to another when no trees are around would be very simple and fast. Once you have a lot of trees, going from one point to another would take much longer time, because you must go around the trees. So this sort of signaling is much slower than signaling at synapses, but eventually the neuropeptides will reach most parts of the brain. However, only brain areas that have the right receptors can respond to the neuropeptides. So release of neuropeptides by dendrites, like Wi-Fi, is a wireless signal—these messages are “public announcements” that are not sent from one cell to another, but from one group of neurons to another group of neurons [1].

• Figure 2
• Neuropeptides (key) are released into the space between neurons (trees) and diffuse through the brain to reach receptors (locks) that can be on distant targets. Consider diffusion like making your way through a forest. The time it takes to reach your lock (receptor) depends on how many trees (other neurons or cells) you have to go around.

Oxytocin and Vasopressin Can Affect Behavior by “Wireless” Signaling

Let me use another example. The neuropeptides, oxytocin and vasopressin, are made by large neurons in the hypothalamus, a part of the brain that is important in regulating many physiological processes of the body. These large neurons have one axon that goes all the way to a specialized gland, the pituitary gland, which is attached to the bottom of the brain. From there, the neuropeptides are released from the axon terminals directly into the blood. Oxytocin travels through the body and has a role in childbirth and breastfeeding. Vasopressin affects blood pressure and regulates the body’s water balance through the kidneys. But both neuropeptides are also released into the brain, where they control several sorts of behavior. For example, oxytocin helps a mother to bond with her child, and vasopressin affects memory and aggression. However, the brain areas that control these behaviors are sometimes far from the cells that make the neuropeptides. Some of these areas have the right receptors but no axons and terminals nearby, so that “wired” signaling by oxytocin and vasopressin cannot occur.

The oxytocin and vasopressin released from the axon terminals into the blood cannot re-enter the brain because of a strange structure called the blood–brain barrier. Think about it, when you get sick, you do not want bacteria or viruses to invade your brain! The blood–brain barrier is a layer of cells keeping the brain safe from pathogens, toxins, and other molecules circulating in the blood. It prevents invaders from entering the brain.

However, oxytocin and vasopressin are also released from the dendrites of the neurons, directly into the brain. Scientists have discovered that the release of neuropeptides from dendrites (into the brain) and from axons terminals (into the blood) can happen independently. Release of vasopressin and oxytocin from the axon terminals is controlled by action potentials, similar to the neurotransmitter release triggered in all other neurons. However, some chemical signals in the brain can stimulate neuropeptide release from the dendrites without triggering action potentials. Producing release in these different ways allows neuropeptide effects in the body and the brain to be regulated separately. For example, as well as having effects on the body, such as childbirth and breastfeeding, oxytocin also stimulates the mother’s childcare and bonding—actions of the brain. This makes sure that the newborn receives all that is urgently needed: food and love (Figure 3) [2].

• Figure 3
• Oxytocin is released into the blood from axons in the pituitary gland (blue arrow) and into the brain (white arrows) from the dendrites of neurons in the hypothalamus (red area). Oxytocin acts both in the body and in the brain to make sure the child gets food (oxytocin’s action on the body) and love (oxytocin’s action on the brain).

Are Neuropeptides Similar to Hormones?

Release of neuropeptides by the dendrites of neurons is very similar to the release of hormones elsewhere in your body. Hormones are the chemical messengers released by glands and transported by the blood to distant target cells. So, hormones can stimulate cells that are located far away from the glands where they are produced. There are many different hormones, and they have lots of different functions in the body. For example, prolactin, another hormone released from the pituitary gland, travels to a mother’s breast where it stimulates the production of milk for breastfeeding. This process of “wireless signaling” by hormones is like the signaling by neuropeptides within the brain—so neuropeptides could be called “brain hormones.”

Why is it Important to Understand Neurotransmitter Signaling?

Some of the behavior disorders hardest to treat, for which new therapies are urgently needed, affect behaviors in which vasopressin and oxytocin are involved [3]. As mentioned above, oxytocin is involved in childbirth, breastfeeding, and the mother’s behavior toward childcare. But oxytocin is also important for the child to develop and maintain complex interactions with others. Some children with autism often have difficulties in understanding and responding to those interactions, and scientists are trying oxytocin as a potential treatment (if you want to learn more about this, read the article written by Daniel Quintana and Gail Alvares in the Frontiers for Young Minds online library) [4].

Other examples include disorders associated with stress and anxiety, disorders of eating, disorders of substance misuse (including alcohol misuse), and disorders of sexual behavior. These are major health problems with a considerable impact on humans. By better understanding how brain cells and neuropeptides interact, we may find ways to control some of these disorders and improve the quality of our lives.

Glossary

Neuron: ↑ Cells of your nervous system, called nerve cells or neurons, are specialized to transmit “messages.”

Neurotransmitters: ↑ Chemicals used by neurons to talk to each other—we can think of them as “chemical words.”

Neuropeptides: ↑ A special type of neurotransmitter. They influence activities in the brain and body, for example regulating a person’s energy level.

Hypothalamus: ↑ The hypothalamus is a brain region that regulates functions like thirst, appetite, and sleep.

Pituitary Gland: ↑ The pituitary gland is located in a small, bony cavity at the base of the brain. It is connected to the hypothalamus. It secretes hormones regulating many different bodily activities.

Hormones: ↑ Hormones are special chemicals that the body makes to help it do certain things like growing up and going through puberty, which is when you begin developing into an adult. During this time, your body is loaded with hormones that tell it that it is time to start changing.

Autism: ↑ Many kids who have autism have trouble understanding what other people are thinking and how they are feeling. They might act in a way that seems unusual, and it can be hard to understand why they are acting that way.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ludwig M (2017) How Your Brain Cells Talk to Each Other—Whispered Secrets and Public Announcements. Front. Young Minds. 5:39. doi: 10.3389/frym.2017.00039

Submitted: January 19, 2017; Accepted: July 11, 2017; Published online: July 26, 2017.

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