What are neurotransmitters?
Neurotransmitters are chemical molecules synthesized within brain cells, which allow the transfer of signalling messages between brain cells. Whilst the signals which are carried within each cell are electrical, chemicals, such as neurotransmitters, are critical at the joins between cells to enable the transfer of information across the gaps.
There are many major and minor signalling chemicals in the brain. The major neurotransmitters in your brain include glutamate and GABA, the main excitatory and inhibitory neurotransmitters respectively, as well as neuromodulators including chemicals such as dopamine, serotonin, norepinephrine and acetylcholine.
Acetylcholine
What is Acetylcholine?
Acetylcholine (ACh) is an important neurotransmitter in the brain which has a role in how you pay attention, learn and remember. ACh cells are located within collections of nuclei within your brainstem and midbrain such as nucleus basalis, the septum, the substantia innominata, the diagonal band of Broca, pedunculopontine nucleus and laterodorsal tegmental area. From here, the ACh cells extend out to nearly every region of the brain.
How is Acetylcholine synthesized in the brain?
Acetylcholine (ACh) is made in the brain by the enzyme choline acetyltransferase using two chemical compounds - choline and acetyl-CoA. The enzyme first separates the acetyl part from the acetyl-CoA and then joins this with choline to create the acetylcholine - ACh.
How is Acetylcholine synthesized in the brain?
Acetylcholine (ACh) is made in the brain by the enzyme choline acetyltransferase using two chemical compounds - choline and acetyl-CoA. The enzyme first separates the acetyl part from the acetyl-CoA and then joins this with choline to create the acetylcholine - ACh.
What is the function of Acetylcholine in the brain?
Acetylcholine acts both within the brain, where it is important in cognitive processes such as attention, learning and memory, and within the periphery of your nervous system where it is a critical signalling chemical at the interface between your nerves and your muscles.
Dopamine
What is Dopamine?
Dopamine is an important modulatory neurotransmitter in the brain - one of a family of catecholamines which also includes the neurotransmitter norepinephrine (noradrenaline) and the hormone-neurotransmitter epinephrine (adrenaline).
Unlike glutamate and GABA, whose cells are located throughout the brain, dopamine cell bodies are only found in small collections of nuclei within your “midbrain” - such as the ventral tegmental area and substantia nigra. Although the cells within these nuclei have their cell bodies located within these specialized dopamine hubs, their “axons” - the neuronal projections which get sent out of the cell body to connect with other brain cells - extend out into the far reaches of the brain as a diffuse neural network.
In this way, dopamine can comprehensively exert it’s influence over many regions of your brain, modulating the way you think, feel and act.
How is Dopamine synthesized in the brain?
Dopamine is synthesized from the precursor chemical L-Dopa by the enzyme aromatic L-amino acid decarboxylase (also called DOPA decarboxylase). The same enzyme is also used to synthesize serotonin and histamine.
L-Dopa itself is generated from the amino acid L-Tyrosine (by the enzyme tyrosine hydroxylase) a process which requires various other supporting chemicals (called cofactors) including tetrahydrobiopterin (which is also required in the synthesis of several other neurotransmitters) and iron. L-tyrosine can also be synthesized from another amino acid - L-Phenylalanine - which is obtained from your diet.
Dopamine itself cannot easily cross the blood brain barrier and therefore has to be synthesized inside the brain.
Where does Dopamine act in the brain?
There are two families of dopamine receptors - the molecules onto which dopamine binds to exert its effect in the brain. These are called D1 (which includes the D1 and D5 receptors) and D2 (which includes D2, D3 and D4 receptors). These receptors are differentially distributed around the brain and operate in slightly different ways. Within the synaptic space the receptors are located on the surface of the receiving cell (as well as some on the sending cell), awaiting the arrival of dopamine molecules to activate them.
What is the function of Dopamine in the brain?
Because dopamine acts as a neurochemical modulator across multiple regions of the brain, it has the capacity to influence multiple facets of brain functioning. There are several dopamine hubs - the main ones being the ventral tegmental area (which projects to the prefrontal cortex and nucleus accumbens) and the substantia nigra which forms part of your basal ganglia.
Each hub oversees slightly different functions in the brain. For example, the function of the substantia nigra can be observed through the emotional, cognitive and movement disturbances displayed by individuals with Parkinson's disease, due to a depletion of dopamine release from this hub.
One of the major functions of dopamine in the brain is in reward learning and prediction - the mechanism by which you adjust your behaviour based on predictions you make about where, and when, rewards - such as money, pleasure, food or success - might occur in the future.
Norepinephrine
What is norepinephrine?
Norepinephrine (noradrenaline) is a neurotransmitter found in the brain which has very similar in structure to the joint hormone-neurotransmitter epinephrine (adrenaline). It acts both in the brain and body and is generally important in mobilizing you for action. It is the main neurotransmitter of your body’s sympathetic nervous system - the “activating” part of your body’s autonomic nervous system which helps to regulate your body systems in response to changing situational demands.
How is Norepinephrine synthesized in the brain?
Norepinephrine is synthesized from dopamine by the enzyme dopamine beta-hydroxylase. It is synthesized within cells originating from brainstem nuclei such as the locus coeruleus. However, norepinephrine also has body-wide effects (e.g. in the peripheral parts of the nervous system) and is released directly into the bloodstream, via a region called the adrenal medulla, as well as acting in your peripheral nerves when it plays a role in the activation of your body’s sympathetic - ready to react - system.
Where does Norepinephrine act in the brain?
In the brain, noradrenaline acts through two main families of receptors - alpha and beta - each with multiple subtypes. Like the dopamine system, cells within the locus coeruleus project to different brain regions, including the prefrontal cortex, anterior cingulate cortex - a region involved in mental flexibility - and your motor cortex which oversees the way you plan and execute your movements.
What is the function of Norepinephrine in the brain?
Noradrenaline is the chemical in your brain which influences your level of “arousal” - in other words it helps to ramp up your brain systems in readiness for action. It therefore has a generally modulatory effect across a broad range of brain functions including wakefulness, memory and alertness, enabling the brain to respond effectively to any challenges or threats that it encounters.
Norepinephrine is closely related to its hormonal equivalent - epinephrine - which acts not only as a neurotransmitter in the brain, but also as a hormone in the body acting via adrenoreceptors. This ensures that the body, as well as the brain, is ready to deal with any physical or emotional stressors and elicits a characteristic set of body-wide changes which together form what is more commonly known as the “fight or flight” response.
Serotonin
What is Serotonin?
Serotonin is a key monoamine neurotransmitter in the brain. The main serotonin hub in the brain is the raphe nucleus but there are others including the caudal linear nucleus, and nucleus pontis centralis oralis and the area postrema. Each group of cell bodies have a slightly different pattern of connectivity within the brain.
How is Serotonin synthesized in the brain?
Serotonin (5-HT) synthesis is dependant on the availability of its precursor, the amino acid L-tryptophan, which is converted into serotonin via 5-Hydroxytryptophan (5-HTP) along a metabolic pathway involving two enzymes, tryptophan hydroxylase and amino acid decarboxylase. Serotonin cannot pass the blood brain barrier, but its precursor - tryptophan - can in some instances be transported across if it is present in sufficient amounts relative to other amino acids which compete at the blood brain barrier for access into the brain.
Where does Serotonin act in the brain?
There are multiple families of serotonin receptors, with each family containing multiple subtypes. These include 5-HT1A/1B/1D/1E/1F, 5-HT2A/2B/2C, 5-HT3A/3B, 5-HT4A/4B/4C/4D, 5-HT5A/5B, 5-HT6 and 5-HT7A/7B/7C/7D. The receptors vary according to where they are expressed in the brain.
In addition, each one has a different genetic origin which means that two people can express a slightly different combination and pattern of serotonin receptors throughout their brain depending on their specific genetic makeup. Serotonin is released into the synaptic space and binds to the receptors which are typically located on the surface of the receiving cell.
What is the function of Serotonin in the brain?
Like dopamine, serotonin has a modulatory function and exerts its effect across many different brain regions. It therefore doesn’t have a specific function but instead “tweaks”, your brain activity over a wide spectrum of cognitive, emotional, physiological and metabolic systems, to help regulate them. This includes your mood, sleep and wakefulness, appetite, level of aggression, circadian rhythms, body temperature, and neuroendocrine function.
GABA
What is GABA?
GABA is the brain’s main inhibitory neurotransmitter. This means that when it binds to receptors on the receiving cell, instead of telling the cell to “fire”, it instead tells it not to. In doing so, it inhibits the continuation of the message along that particular neural pathway. GABA therefore makes sure that the brain doesn’t send signals “too easily”, helping to keep your brain’s overall level of neural activity in check.
How is GABA synthesized in the brain?
GABA is synthesized from glutamate, the brain's main excitatory neurotransmitter by the enzyme glutamic acid decarboxylase (GAD). Its synthesis also requires a supporting chemical - a cofactor - called pyridoxal phosphate, which is derived from vitamin B6 taken in from your diet. As GABA levels rise in the brain, it inhibits the action of GAD, therefore regulating its own rate of synthesis.
GABA is released not only from inhibitory cells, but also from supporting brain cells called glia, and is also often “co-released” together with other neurotransmitters. The mechanism of GABA release in the brain is further complexified by the fact that it can be released from both ends of a brain cell (the axons and the dendrites).
The multiple modes of GABA release helps to ensure that it can dynamically fine tune its response according to the ongoing neural environment. Again, like glutamate, GABA finds it difficult to cross the blood-brain barrier when it is not required, therefore helping to keep levels of GABA in the brain tightly regulated.
Where does GABA act in the brain?
GABA acts via two receptor families - GABA-A and GABA-B. These receptors are located not only on the surface of the receiving cell, but also on the sending cell which means that when GABA is released into the synaptic cell it not only regulates the onward signal in the receiving cell (inhibiting it) but also influences the operations within the sending cell itself.
GABA cells are located throughout the brain and act in various ways, including blocking entire signaling pathways (e.g. in sleep) or by fine-tuning neural firing responses to make sure that only the most relevant information is carried forward, whilst less relevant information - the “noise” from surrounding brain cells - is blocked, or inhibited. This “lateral inhibition” is a neural mechanism that is commonly found in your brain’s sensory processing systems to make sure that important information is highlighted to the brain.
What is the function of GABA in the brain?
GABA is implicated in a wide variety of functions to fine tune neural processing. It is also broadly involved in supporting sleep (e.g. by inhibiting wake-promoting regions) and a disturbance in GABA signalling is one contributing factor in anxiety disorders, which can be treated using benzodiazepines which act to increase GABA signalling in the brain, therefore reducing unwanted brain excitability.
Glutamate
What is glutamate?
Glutamate, or glutamic acid, is one of the most abundant amino acids in the human brain and has an excitatory action. This means that when it binds to complementary receptors located on the receiving cell, it leads to the “activation” of that cell. If you have too much glutamate in your brain then it can result in the death of your brain cells (it becomes toxic at high concentrations), and therefore the levels of glutamate need to be closely regulated to ensure that the brain doesn’t become “overstimulated”.
How is glutamate synthesized in the brain?
Glutamate is reciprocally synthesized from the molecule glutamine, another amino acid which is created when glutamate is degraded, by the enzyme glutaminase. Because of the toxic nature of too much glutamate, it is usually kept locked up inside your brain cells and only released when required. In addition, the amino acid glutamate does not easily pass through the blood brain barrier when it is not needed which allows further control for ensuring the glutamate levels in the brain do not become too high.
Where does glutamate act in the brain?
There are two major types of glutamate receptors in the brain - NMDA receptors (N-methyl-d-aspartate) and AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid). Glutamate, when it is released, binds to these receptors to mediate its excitation of the receiving cell. The two receptors types have slightly different modes of action, with the AMPA receptors typically eliciting a rapid response after the glutamate binds, whilst NMDA receptors are more slow to act and need slightly more persuasion from the glutamate to elicit a response.
What is the function of glutamate in the brain?
As glutamate is the main excitatory neurotransmitter in the brain it is present to some degree in nearly all brain regions. It also has a specific role in a neural mechanism called synaptic plasticity.
Synaptic plasticity is important for the way we learn. This is because it can strengthen or weaken individual synapses (i.e. increase the power of the resulting signals which are carried onwards from the synapse). In doing so synaptic plasticity updates and adjusts the brain’s connectivity patterns to take into account newly learned information, which needs to be stored into memory - in essence underpinning the concept of having a “plastic” brain.Synaptic plasticity has been shown to require glutamate-sensitive NMDA and AMPA receptors.