Video: Neurotransmitters

Would you believe that these tiny molecules are behind your every thought, feeling, and movement? Imagine your body is a high-speed data center and neurotransmitters are the little messengers zipping around, delivering crucial messages which keep our bodies in sync. From the simple act of wiggling your fingers to the complex emotions of love and joy, neurotransmitters are the key to making it all happen.

So let's dive deeper into the world of neurotransmitters.

Neurotransmitters are chemical substances which neurons use to communicate with one another and with other cell types in the process known as synaptic transmission or neurotransmission. These small molecules are crucial for communicating sensory, motor, and integrative neuronal messages, affecting many functions, such as emotions, thoughts, memories, and movements.

So let's first have a closer look at their mechanism of action.

The process by which neurons communicate with their target tissues using neurotransmitters is called chemical neurotransmission which occurs within specialized junctions called synapses. Each synapse consists of a presynaptic membrane, which is the membrane of the terminal bouton of the presynaptic nerve fiber; a postsynaptic membrane, which is the membrane of the target cell; and the synaptic cleft, which is the gap between the presynaptic and postsynaptic membranes.

Within the terminal bouton of the presynaptic neuron, numerous synaptic vesicles that contain neurotransmitters are produced and stored. An action potential reaching the presynaptic terminal results in exocytosis of synaptic vesicles and the neurotransmitters are released into the synaptic cleft. After crossing the synaptic cleft, neurotransmitters bind to receptors on the postsynaptic membrane, leading to a stimulatory or inhibitory response in the target cell, depending on the type of neurotransmitter in question.

There are generally considered to be two types of neurotransmitter receptors: ionotropic and metabotropic.

Ionotropic receptors are typically ligand-gated ion channels through which ions pass in response to the binding of a chemical messenger, also referred to as a ligand, such as a neurotransmitter. Ionotropic receptors are fast-acting, leading to fast synaptic transmission and mediating fast transient responses.

Metabotropic receptors, on the other hand, do not form an ion channel pore, but instead require G proteins and secondary messengers to indirectly modulate ionic activity in neurons. G-protein-coupled receptors represent the largest family of metabotropic receptors.

Since opening channels by metabotropic receptors involves activating a number of molecules in the intracellular mechanism, these receptors are slower acting than their ionotropic counterparts, but at the same time are involved in more prolonged effects on cellular function.

Now there are more than 60 neurotransmitters in the human nervous system, so let's have a look at how they are broadly classified into groups.

Firstly, they can be classified based on their chemical structure. In this classification system, the main groups are the monoamines, amino acids, neuropeptides, and an others group that contains neurotransmitters that don't quite neatly fit into the more well-defined first three groups.

Looking at the monoamines first, they're relatively small molecules comprising only a few atoms, allowing them to easily diffuse across synaptic clefts. They are involved in things like coordinating movement, regulating mood, sleep, alertness, and various autonomic functions. This group includes dopamine, epinephrine, norepinephrine, histamine, and serotonin.

The second group contains the amino acids which, like monoamines, are relatively small molecules. While both can easily diffuse across synaptic clefts, amino acids are slightly larger due to their more complex side chains. Amino acid neurotransmitters are vital for excitatory and inhibitory signaling, sensory processing, motor control, neural development, and synaptic plasticity. This group includes glutamate, GABA, and glycine.

The third class, neuropeptides, are a group of larger and more complex neurotransmitters. As their name suggests, they are composed of peptide chains rather than being modified amino acids. This distinction is important because it dictates their site of synthesis.

Unlike smaller neurotransmitters such as monoamines and amino acids which can be synthesized within the axon terminal, neuropeptide production requires organelles that are only found in the neuron cell body which the axon terminals lack. Therefore, neuropeptides are produced in the cell body where they are then packaged into large dense core vesicles before becoming reduced in size by enzymatic cleavage during their transport to sites of release.

Neuropeptides play a role in modulating pain perception, stress response, appetite regulation, reproductive functions, sleep, learning, and immune responses. Some of the main neurotransmitters in this group include substance P, neuropeptide Y, endorphins, enkephalins, vasopressin, and oxytocin.

The others group of neurotransmitters encompasses a diverse range of substances that do not fit neatly into the major categories, each with unique structural properties and mechanisms of action. This group include small molecules such as acetylcholine and can include gases like nitric oxide and lipids like endocannabinoids.

In addition to the structural classification of neurotransmitters just discussed, often it can be actually more useful to classify neurotransmitters based on their function. In this system, there are two main groups: excitatory and inhibitory neurotransmitters. It should be noted that many neurotransmitters can have both excitatory or inhibitory effects, depending on the specific postsynaptic receptors they bind to. However, in this tutorial, we will be mentioning the most common effect of each neurotransmitter.

Excitatory neurotransmitters function to activate receptors on the postsynaptic membrane which leads to depolarization of the neuron and increases the likelihood that it will itself then reach the threshold to fire its own action potential, promoting communication within neural circuits. Some of the major excitatory neurotransmitters include glutamate, acetylcholine, epinephrine and norepinephrine, and serotonin.

Inhibitory neurotransmitters, on the other hand, function to prevent an action potential by hyperpolarizing the postsynaptic neuron, making it less likely to reach the threshold needed for firing its own action potential, thereby dampening neuronal excitability. Some of the major inhibitory neurotransmitters include GABA, glycine, and serotonin, which, as we can see, is an example of a major neurotransmitter that can be classified as either excitatory or inhibitory based on the receptor it binds to.

So let's take a closer look at some of the most common and well-understood neurotransmitters in the body.

First up is acetylcholine, a predominantly excitatory neurotransmitter produced by cholinergic neurons with its main function being to stimulate muscle contraction while it also plays a role in regulating the sleep cycle. However, it should be noted that it also does have an inhibitory role on the heart where it reduces heart rate.

Next, we have norepinephrine, also known as noradrenaline, which is an excitatory neurotransmitter. It is produced in this small area of the brainstem, which is called locus coeruleus, as well as the adrenal glands, and it is involved in regulating attention, arousal, and the body's response to stress. Abnormally low levels of norepinephrine have been implicated in mood disorders such as depression and anxiety. Alternatively, abnormally high concentrations may lead to an impaired sleep cycle.

Epinephrine, also known as adrenaline, is also an excitatory neurotransmitter produced in the medulla of the adrenal gland. It's responsible for rapidly preparing the body for the fight or flight response by including increasing heart rate, dilating airways, and mobilizing energy stores.

Now, dopamine, which is secreted in the substantia nigra, is considered to be a special type of neurotransmitter because its effects can be either excitatory or inhibitory, depending on the type of receptor that it binds to. Functionally, it's important for movement coordination by inhibiting unnecessary movements as well as inhibiting the release of prolactin and stimulating the secretion of growth hormone.

A deficiency in dopamine that is related to the destruction of the substantia nigra leads to a common neurodegenerative disease called Parkinson's disease, whereas an increased activity of dopaminergic neurons contributes to the pathophysiology of psychotic disorders and schizophrenia.

Gamma-aminobutyric acid, commonly referred to as simply GABA, is the most powerful inhibitory transmitter of the nervous system and is essential for maintaining the balance of excitation and inhibition throughout the nervous system. Functions of GABA are closely related to mood and emotions, where abnormally low levels of GABA can lead to anxiety.

Glutamate is the most common and powerful excitatory neurotransmitter in the central nervous system, being secreted by several excitatory neurons in the central nervous system and playing a crucial role in maintaining homeostasis alongside the inhibitory effects of GABA. In addition, glutamate is also linked to cognitive functions such as learning and memory formation. Inappropriate glutamate neurotransmission can contribute to the development of epilepsy as well as cognitive and affective disorders.

Next, we have serotonin, which is another type of neurotransmitter that can be both excitatory or inhibitory and is primarily secreted by the neurons of the brainstem and those that innervate the gastrointestinal tract. It plays a critical role in various physiological and psychological processes in the body including the regulation of body temperature, perception of pain, emotions, and sleep cycle. An insufficient secretion of serotonin may result in decreased immune system function as well as a range of emotional disorders including depression and anger control problems.

And finally, we have histamine, which is an excitatory neurotransmitter produced by neurons of the hypothalamus, cells of the stomach mucosa, mast cells, and basophils in the blood. It's primarily involved in the body's inflammatory response and is a key mediator in allergic responses leading to symptoms such as itching, sneezing, runny nose, and hives when released in excess during an allergic reaction.

And that concludes our tutorial on neurotransmitters.

To revise this content, be sure to check out the quiz and other learning materials in the study unit on this topic. See you next time!