A Guide to Neurotransmitter Balance


1. NEUROTRANSMITTERS

  1. 1.1 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.

  2. 1.2 How does neurotransmitter signalling work?

    Neurotransmitters are typically released from the surface of one brain cell - the sending cell - into an extracellular space which forms part of the “synapse” - which connects two brain cells. Once they have been released into the synapse, various things can happen to the neurotransmitter molecule, but the main aim is for the neurotransmitter to reach the “other side” of the extracellular space and bind onto specific proteins - called receptors - which are typically located on the surface of the receiving brain cell. When the neurotransmitter “binds” to these receptors, it sets up a cascade of chemical reactions within that receiving cell which ultimately results in the continuation of the electrical signal along that cell and further into the brain. Each synapse - and there are 100-1000s of trillions of them in your brain - acts as a critical interface where your brain can regulate the chemical and electrical balance - your neural homeostasis - as your brain is busy at work.

  3. 1.3 What are the main neurotransmitters in the brain?

    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.

2. NEUROTRANSMITTER BALANCE

  1. 2.1 What is the ideal state of neurotransmitter balance? How does this change throughout the day?

    Each neurotransmitter system does not operate in isolation. Instead there is a careful balance of overall neurochemistry where too much, or too little, of any of one neurotransmitter upsets the entire balance of the brain. This unbalancing manifests itself as changes in the way you think, feel and behave - the mental highs and lows of your daily life. Changes in the different levels of neurotransmitters can be transient - altered by a particular event or experience that happens to you during your day, or more enduring as an ongoing neurochemical ebb and flow from morning to night, typically in line with your in-built circadian rhythm. One of the major juggling acts is between the level of excitation and inhibition in the brain, mediated by the corresponding levels of the neurotransmitters glutamate and GABA. A breakdown in this balance has been implicated in a number of neurological disorders including Epilepsy, Schizophrenia, Autistic Spectrum Disorder and the experience of Migraine.

    The brain is constantly striving to keep your different neurochemical systems in balance in response to your ongoing internal and external needs - something that it does through constant neurobiological and synaptic shifts which alter the levels of different neurotransmitters. For example during the night when you need to sleep, the inhibitory neurotransmitter GABA blocks the activity of other neurotransmitter systems, shifting the balance in it’s favor. In contrast, during the day when you need to think and react, the brain rebalances itself so that these other neurotransmitter systems stop being under sleep-based inhibitory control and are more free to send messages through their respective neural systems.

  2. 2.2 What mechanisms does the brain put in place to maintain its balance of neurotransmitters?

    The brain uses various mechanisms to maintain a healthy balance of neurotransmitters and ensure that the brain’s response doesn’t get out of hand, especially in situations when it is under neurophysiological strain - either from a positive or negative perspective. These include:

    1. 2.2.1 The blood brain barrier
      The brain's blood brain barrier is a gateway into the brain and is very strict about which chemicals it will allow in - something that is controlled by the array of transporter proteins and chemical gates located within it, which all operate within specific parameters.
    2. 2.2.2 Transporter Reuptake Proteins
      Within the synaptic space there are transporter proteins which are there to mop up any excess neurotransmitters, or to quickly remove the neurotransmitter once it is no longer required.
    3. 2.2.3 Supporting Glial Cells
      Although much of the focus is on the neurons which carry the signals around the brain, the supporting cells which help them to do this - the glia - play an important role in ensuring that neurotransmitter balance is maintained within the brain.
    4. 2.2.4 Release mechanisms
      Neurotransmitter release from the sending neurons is a tightly controlled process to make sure not too much neurotransmitter is released into the synapse at any one time.
    5. 2.2.5 Rate limiting enzymes
      The enzymes which synthesize and degrade the neurotransmitters are rate limiting in their mode of action which means that the speed at which neurotransmitters are generated and broken down can be tightly controlled.
    6. 2.2.6 Inter-dependent precursors
      The synthesis of neurotransmitters is part of a carefully constructed cycle, where the precursors and the end products are interdependent. For example, inhibitory GABA is synthesized from excitatory Glutamate. This means that each neurotransmitter isn’t synthesized in isolation but as part of a wider process of balancing the brain's overall neurochemistry.
  3. 2.3 What environmental factors influence your brain’s neurotransmitter balance?
    1. 2.3.1
      Diet. Maintaining a healthy balance of neurotransmitters requires a healthy balanced diet. This provides the brain with the necessary neurochemical building blocks, as well as the appropriate chemicals which are required to support their synthesis, transportation and degradation. This includes ensuring the brain has sufficient energy supplies (e.g. from carbohydrates and fats which ultimately help to form energy-generating ATP molecules), amino acids, and the various vitamins and minerals which are cofactors in the enzymatic pathways. Although many of the neurotransmitters cannot easily cross the blood-brain barrier, their amino acid precursors, in some instances, can do so, providing a potential route for influencing the concentration of precursors in the brain under certain circumstances.

      Although there are various foods which contain neurotransmitters and their amino acid precursors, their ability to modify the brain’s response depends on how easily they can cross the blood-brain barrier - the gateway from the body (specifically the bloodstream) into the brain. GABA and Glutamate require a significant concentration differential between the blood and brain to be allowed in. Neurotransmitters like dopamine and serotonin cannot cross the blood-brain barrier because it does not contain the necessary “transport” mechanisms needed to get them across. In contrast, in some instances, their precursor amino acids can cross the blood brain barrier. But because the amino acids often compete against each other to determine which one gets to cross, it is the relative levels of the amino acids which is important, not just the absolute levels ingested.

    2. 2.3.2
      Medication and Drugs. Medications and drugs can act to disrupt your brain’s neurotransmitter balance, or compensate for its imbalance. They can act at various points of the synapse to either mimic the effects of the neurotransmitter (e.g amphetamine acting on catecholamine receptors), to enhance their effects of the neurotransmitter (e.g. benzodiazepines potentiate the action of GABA receptors) or to prevent their reuptake (as is the case with cocaine and catecholamines or Prozac and serotonin). Other drugs work to block (antagonize) receptors, for example the action of the beta-blocker propranolol on noradrenergic and adrenergic receptors.
    3. 2.3.3
      Chronic Stress. Your body’s physiological stress response is mediated, in part, by the steroid hormone cortisol, released as a result of the activation of a brain-body pathway called the hypothalamic-pituitary-adrenal axis. Although a small amount of stress is often considered a useful way of raising your “get up and go”, feeling stressed all the time - so called chronic stress - more profoundly disrupts your neurochemical balance.

      One neurotransmitter which is particularly badly affected is glutamate, your brain’s primary excitatory neurotransmitter. Being chronically stressed causes more glutamate than normal to be released at synapses in the brain’s prefrontal regions - involved in higher-order thinking - and hippocampus - a region involved in memory. It also interferes with how effectively glutamate is cleared away from the synapse when it is no longer required. Too much glutamate in these regions results in cognitive impairments especially in relation to the way you learn and remember. Chronic stress also reduces the level of serotonin in the brain, in part explaining the link between chronic stress and depressive disorders.

  4. 2.4 What is the effect of having a neurotransmitter imbalance?

    The consequences of having a neurotransmitter imbalance depends on how extreme the imbalance is, but generally most clinical disorders involving the brain have some degree of neurotransmitter imbalance - whether that be too little of a particular neurotransmitter, or in some instances, too much. Examples of this include dopamine depletions in Parkinson’s disease, serotonin depletions in depression, GABA depletions in anxiety, acetylcholine depletions in Alzheimer's disease and glutamate and GABA imbalance in epilepsy.

    In addition, more transient fluctuations in neurotransmitters imbalance can cause changes across a wide range of behaviours including your mood, your ability to sleep properly, your attentional focus and ability to remember information, or your motivational state, to name a few.

  5. 2.5 How do we correct neurotransmitter imbalances?
    1. 2.5.1 Targeted Amino Acid Therapies

      Targeted amino acid therapies are when supplements of a particular neurotransmitter are given to an individual to try and combat any perceived imbalances in the brain's’ neurotransmitter systems.

      Targeted amino acid therapies work by substantially altering the relative balance of amino acids ingested within your diet. They are based around the finding that subtle change in dietary intake are not usually sufficient to alter levels of particular neurotransmitters in your brain because they do not go far enough to increase the concentration of a particular amino acid over and above others to allow it to preferentially cross the blood-brain barrier. This is necessary because of the competitive interactions between amino acids trying to cross the blood brain barrier. Supplementing a particular amino acid aims of disrupt this balance to promote the uptake of that amino acid, over others, into the brain.

    2. 2.5.2 Exercise

      It is well established that exercise is good for the health of your body. It is also good for your brain, improving the way you think and feel across a number of different metrics. One reason for this is due to the way exercise influences your brain’s neurochemical balance by altering the levels of monoamine neurotransmitters such as serotonin, dopamine and noradrenaline. Serotonin, and to some degree dopamine, are involved in what is called “central fatigue” - the process by which your brain feels tired after strenuous or prolonged exercise. Doing high-intensity exercise increases the availability of brain tryptophan and promotes the synthesis of serotonin which, in combination with changes in the other monoamine neurotransmitter systems, mediates the behavioural sensations of fatigue and subsequent positive changes in mood.

    3. 2.5.3 Light Therapy

      Light therapy has also been used to try and manipulate the levels of neurotransmitters in the brain. One of the most commonly targeted systems in serotonin due to its role in depressive disorders such as Seasonal Affective Disorder. Therapeutic interventions which artificially simulate the “lux” level of natural light have been shown to prevent a decline in mood in situations where there is an insufficient supply of tryptophan - the main precursor to serotonin. Because of the “entraining” effect of light, it has also been used to treat disorders where there is a disruption in the natural circadian rhythm. However, the timing of the light therapy is critical to it’s effectiveness and has to be aligned against your in-built circadian rhythm to avoid further disruption of the natural ongoing metabolic cycles within your body and brain.

3. DETAILED GUIDE TO NEUROTRANSMITTERS

  1. 3.1 Glutamate (Excitatory)

    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.

    How is glutamate broken down in the brain?
    Glutamate is not broken down by enzymes immediately located in the synaptic space between the two brain cell. Instead it is first taken into a nearby brain cell. There are specific proteins located on the surface of the sending and receiving cell (and in particular on surrounding glial support cells) which are tasked with making sure the level of glutamate in the synapse doesn’t become too high. These “transporter systems” (and there are multiple types of them) remove glutamate from the synaptic space. preventing it from having its excitatory effect. This ensures that glutamate levels are tightly controlled and protect the brain from excitotoxic harm. Once glutamate is taken up into the cell is can then be either repackaged ready for being released back into the synapse; used in other cell-based metabolic processes such as the energy-generating tricarboxylic acid cycle; or converted back into glutamine by the enzyme glutamine synthetase.

  2. 3.2 GABA [Inhibitory]

    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.

    1. 3.2.1 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.

    2. 3.2.2 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.

    3. 3.2.3 How is GABA broken down in the brain?

      Once GABA has been released, it is taken up by transporter proteins which remove it from the synaptic space and store it either in the surrounding neurons, or the supporting glial cells. Within the cell, GABA is then broken down into the metabolite succinate by two sequential enzymes the first one being GABA-transaminase, followed by succinic semialdehyde dehydrogenase.

  3. 3.3 Dopamine [Excitatory/Inhibitory]
    1. 3.3.1 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.

    2. 3.3.2 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.

    3. 3.3.3 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.

    4. 3.3.4 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.

    5. 3.3.5 How is Dopamine broken down in the brain?

      Dopamine is removed from the synaptic space using dopamine transporters - or DATs - which are mainly located on the surface of the “sending” cell. Once within the cell, the dopamine is either repackaged in readiness for being released again in the future, or is degraded. Dopamine is broken down by a series of enzymes including monoamine oxidase (MOA), catechol-O-methyl transferase (COMT), and aldehyde dehydrogenase (ALDH) into metabolites such as 3,4-Dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA).

  4. 3.4 Norepinephrine [Excitatory]
    1. 3.4.1 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.

    2. 3.4.2 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.

    3. 3.4.3 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.

    4. 3.4.4 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.

    5. 3.4.5 How is Norepinephrine broken down in the brain?

      Once it is no longer required within the synaptic space, norepinephrine is taken back into the cells surrounding the synaptic space using transporter mechanisms. Once within the cell, it is recycled or broken down by enzymes such as monoamine oxidase (MOA) or catechol-O-methyl transferase (COMT) into metabolites such as Vanillylmandelic acid (VMA).

  5. 3.5 SEROTONIN
    1. 3.5.1 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.

    2. 3.5.2 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.

    3. 3.5.3 Where does Serotonin act in the brain?

      There are at 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.

    4. 3.5.4 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.

    5. 3.5.5 How is Serotonin broken down in the brain?

      Once it has completed its action within the synaptic space, serotonin is taken back up into the surrounding cells using specific transporter mechanisms embedded within the surface of the cell. It is these reuptake mechanisms which are the target of drugs such as selective serotonin reuptake inhibitor (SSRIs) including the antidepressant drug Prozac which acts to prolong the duration of serotonin with the synaptic space. Once within the cell, serotonin is then broken down into metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) by the enzyme monoamine oxidase (MOA). 5-hydroxyindoleacetic acid can be measured in your urine and can be used as an indirect marker of your body’s serotonin levels.

  6. 3.6 ACETYLCHOLINE
    1. 3.6.1 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.

    2. 3.6.2 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.

    3. 3.6.3 Where does Acetylcholine act in the brain?

      There are two major families of receptors that ACh can bind to. One family of receptors are called “nicotinic”, and it is at these receptors where the drug nicotine, commonly found in tobacco, acts to mimic the effect of ACh. The other family of receptors are called “muscarinic”. Muscarinic receptors are most often associated with controlling your body muscles as you move about, but are also found in the brain. As with most other neurotransmitter in the brain, there are also multiple variants - subtypes - of muscarinic receptors and nicotinic receptors which have subtle differences in terms of their brain-wide expression and precise mode of action.

    4. 3.6.4 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.

    5. 3.6.5 How is Acetylcholine broken down in the brain?

      Unwanted ACh within the synapse is broken down into choline and acetate by the enzyme acetylcholinesterase. This choline is then taken back up into nearby cells and converted into phosphocholine or stored in the cell surface ready for future conversion into ACh. Some drugs can act to block the action of acetylcholinesterase which, when it occurs at the junction between your nerves and your muscles, can cause a toxic build up of ACh, leading to muscle paralysis.