Introduction    Neurotransmission    Action Potential    Synaptic Signal    Neurotransmitters    Pre-synaptic Control    Disorders of the Brain  
  References  
 

More maps of the brain
    Forebrain
    Midbrain
    Hindbrain
    Spinal cord
    Lobes
    Limbic system
    Coronal section
    Cerebral vasculature

 

Neurological Control

Neurotransmitters

More information on:
Neurotransmission at a synapse

 

 

Neurotransmitter Molecules

Neurotransmitters can be broadly split into two groups – the ‘classical’, small molecule neurotransmitters and the relatively larger neuropeptide neurotransmitters. Within the category of small molecule neurotransmitters, the biogenic amines (dopamine, noradrenaline, serotonin and histamine) are often referred to as a discrete group because of their similarity in terms of their chemical properties.

Small molecule neurotransmitters

Type

Neurotransmitter

Postsynaptic effect

 

Acetylcholine

Excitatory

Amino acids

Gamma amino butyric acid GABA

Inhibitory

Glycine

Inhibitory

Glutamate

Excitatory

Aspartate

Excitatory

Biogenic amines

Dopamine

Excitatory

Noradrenaline

Excitatory

Serotonin

Excitatory

Histamine

Excitatory

Click on the links in the table above to read more about some of the important neurotransmitters.

Neuropeptide neurotransmitters

Corticotropin releasing hormone

Corticotropin (ACTH)

Beta-endorphin

Substance P

Neurotensin

Somatostatin

Bradykinin

Vasopressin

Angiotensin II

 

Serotonin

Although the CNS contains less than 2% of the total serotonin in the body, serotonin plays a very important role in a range of brain functions. It is synthesised from the amino acid tryptophan.

Within the brain, serotonin is localised mainly in nerve pathways emerging from the raphe nuclei, a group of nuclei at the centre of the reticular formation in the
Midbrain, pons and medulla. These serotonergic pathways spread extensively throughout the brainstem, the cerebral cortex and the spinal cord. In addition to mood control, serotonin has been linked with a wide variety of functions, including the regulation of sleep, pain perception, body temperature, blood pressure and hormonal activity.

Outside the brain, serotonin exerts a number of important effects, particularly involving the gastrointestinal and cardiovascular systems.

Noradrenaline

Noradrenaline is classed as a monoamine neurotransmitter and noradrenergic neurons are found in the locus coeruleus, the pons and the reticular formation in the brain. These neurons provide projections to the cortex, hippocampus, thalamus and midbrain. The release of noradrenaline tends to increase the level of excitatory activity within the brain, and noradrenergic pathways are thought to be particularly involved in the control of functions such as attention and arousal.

Outside the brain, noradrenaline plays an important role in the sympathetic nervous system – the system that co-ordinates the ‘fight or flight’ response. Systemically, therefore, changes in noradrenergic activity may induce changes in a range of functions including heart rate, blood pressure and gastrointestinal activity.  This explains the broad side-effect profile associated with drugs that affect monoamine neurotransmitters, such as the tricyclic antidepressants.

Camera iconFind out more about noradrenaline and serotonin

Dopamine

Dopamine is also classed as a monoamine neurotransmitter and is concentrated in very specific groups of neurons collectively called the basal ganglia. Dopaminergic neurons are widely distributed throughout the brain in three important dopamine systems (pathways): the nigrostriatal, mesocorticolimbic, and the tuberohypophyseal pathways. A decreased brain dopamine concentration is a contributing factor in Parkinson’s disease, while an increase in dopamine concentration has a role in the development of schizophrenia.

Acetylcholine

Acetylcholine ‘acts’ or ‘is transmitted’ within cholinergic pathways that are concentrated mainly in specific regions of the brainstem and are thought to be involved in cognitive functions, especially memory. Severe damage to these pathways is the probable cause of Alzheimer’s disease.

Outside the brain, acetylcholine is the main neurotransmitter in the parasympathetic nervous system – the system that controls functions such as heart rate, digestion, secretion of saliva and bladder function. Drugs that affect cholinergic activity produce changes in these body functions. Some antidepressants act by blocking cholinergic receptors and this anticholinergic activity is an important cause of side effects such as dry mouth.

Neurotransmitter Receptors

Neurotransmitters exert their effect by binding to specific receptors on the neuronal postsynaptic membrane. A neurotransmitter can either ‘excite’ its neighbouring neuron so increasing its activity, or ‘inhibit’ its neighbouring neuron, suppressing its activity. In general, the activity of a neuron depends on the balance between the number of excitatory and inhibitory processes affecting it, and these can occur simultaneously. Most neurotransmitter receptors can be divided into two types – ligand-gated receptors and G-protein linked receptors.
Stimulation of a ligand-gated receptor enables a channel in the receptor to open and permits the influx of chloride and potassium ions into the cell. The positive or negative charges that enter the cell either excite or inhibit the neuron. Ligands for these receptors include excitatory neurotransmitters, such as glutamate and, to a lesser extent, aspartate. Binding of these ligands to the receptor produces an excitatory postsynaptic potential (EPSP). Alternatively, binding of inhibitory neurotransmitter ligands, such as GABA and glycine, produces an inhibitory postsynaptic potential (IPSP). These ligand-gated receptors are also known as ionotropic or fast receptors.
G-protein linked receptors are indirectly linked to ion channels, via a second messenger system involving G-proteins and adenylate cyclase. These receptors are neither precisely excitatory nor inhibitory and modulate the actions of the classic excitatory and inhibitory neurotransmitters such as glutamate and glycine. These receptors tend to have an inhibitory effect if they are linked to the Gi protein in the cell membrane, and a more excitatory effect if linked to the Gs protein. G-protein linked receptors are known as metabotropic or slow receptors and examples include GABA-B, glutamate, dopamine (D1 and D2), 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A,
5-HT2C receptors.

Serotoning receptors

Type

Distribution

Postulated Roles

5-HT1

Brain, intestinal nerves

Neuronal inhibition, behavioural effects, cerebral vasoconstriction

5-HT2

Brain, heart, lungs, smooth muscle control, GI system, blood vessels, platelets

Neuronal excitation, vasoconstriction, behavioural effects, depression, anxiety

5-HT3

Limbic system, peripheral neural system

Nausea, anxiety

5-HT4

CNS, smooth muscle

Neuronal excitation, GI

5-HT5, 6, 7

Brain

Not known

Noradrenaline receptors

Type

Distribution

Postulated Roles

Alpha1

Brain, heart, smooth muscle

Vasoconstriction, smooth muscle control

Alpha2

Brain, pancreas, smooth muscle

Vasoconstriction, presynaptic effect in GI (relaxant)

Beta1

Heart, brain

Heart rate (increase)

Beta2

Lungs, brain, skeletal muscle

Bronchial relaxation, vasodilatation

Beta3

Postsynaptic effector cells

Stimulation of effector cells

Dopamine receptors

Type

Distribution

Postulated Roles

D1, 5-like

Brain, smooth muscle

Stimulatory, role in schizophrenia?

D2, 3, 4-like

Brain, cardiovascular system, presynaptic nerve terminals

Inhibitory, role in schizphrenia?

Acetylcholine receptors

Type

Distribution

Postulated Roles

M1

Nerves

CNS excitation, gastric acid secretion

M2

Heart, nerves, smooth muscle

Cardiac inhibition, neural inhibition

M3

Glands, smooth muscle, endothelium

Smooth, muscle contraction, vasodilation

M4

?CNS?

Not known

M5

?CNS?

Not known

NM

Skeletal muscles neuromuscular junction

Neuromuscular transmission

NN

Postganglionic cell body dendrites

Ganglionic transmission

Co-transmission

Several different neurotransmitters can be released from a single nerve terminal, including neuropeptides and small molecule neurotransmitters. As well as acting as neurotransmitters in their own right, neuropeptides can act as co-transmitters. As
co-transmitters, they can activate specific pre- or postsynaptic receptors to alter the responsiveness of the neuronal membrane to the action of ‘classical’ neurotransmitters, such as noradrenaline and serotonin.

Serotonin, noradrenaline and dopamine are involved in the control of many of our mental states, sometimes acting on their own and at other times acting together (illustrated in the diagram below). These and other neurotransmitters are likely to play a pivotal role in the pathological basis of mental illness and diseases of the brain. Much of the evidence for this stems from the fact that most of the effective antidepressant drugs are thought to work by changing either serotonin and/or noradrenaline metabolism, or receptor sensitivity to these neurotransmitters.

Understanding the numerous neurotransmitters, their receptors, locations and interactions with one another has been central to the design of medicines for mental illness. This acquired knowledge has led to the development of successful products for many brain disorders including epilepsy, schizophrenia, Parkinson’s disease, depression, anxiety disorders and migraine.

Monoamine Reuptake and Breakdown

After release from the presynaptic membrane, serotonin and noradrenaline are cleared from the synapse by the process known as reuptake. This terminates the neurotransmitter effect. In addition, ‘used’ monoamines are broken down by enzymes such as monoamine oxidase in the synapse.

 

Last updated: 20.12.2011

 

 

 

 

   Feedback        Site map         Help         Home         Editorial board         Disclaimer