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
Acetylcholine
Amino acids
Excitatory
Gamma aminobutyric acidGABA Inhibitory
Glycine
Glutamate
Aspartate
Biogenic amines
Postsynaptic effect
Dopamine
Inhibitory
Excitatory
Excitatory
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.
Find 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 Parkinsons 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
Alzheimers 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.
Neurotransmitters 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 Gprotein 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, instetinal 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, ANS
Nausea, anxiety
5-HT4 CNS, smooth muscle
Neuronal excitation, GI
5-HT5, Brain
6, 7
Not known
Noradrenaline receptors
Type Distribution
Postulated Roles
Alpha1 Brain, heart, smooth
muscle
Vasoconstriction, smooth muscle
control
Alpha2 Brain, pancreas, smooth Vasoconstriction, presynaptic effect in
muscle
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, 5like
Brain, smooth muscle
Stimulatory, role in
schizophrenia?
D2, 3, 4- Brain, cardiovascular system,
like
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, Parkinsons disease, depression, anxiety
disorders and migraine .
Monoamine Reuptage 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.
