Neurotransmitters
Definition: Neurotransmitters are endogenous
chemicals which transmit signals from a neurone to
a target cell across a synapse, a space of usually 20-
40nm.
Communication between many neurones in an
elaborate, complex signalling network is necessary
to coordinate the complex functions of the nervous
system. This is mediated through the hundreds of
thousands of sites of synaptic contacts – dendritic
spines – within a single neuron. A young developing
brain has ~ 100 billion neurones, and so this means
there are 100-500 trillion synapses overall. Such
signalling between many synapses dictates
personality traits, allows coordination of emotions and memory retrieval,
etc.
The molecular events that occur at these individual synapses hence
control the complex functions of the nervous system.
Axodendritic: the classical synaptic contact between an axon terminal of
one nerve cell and a dendrite of another nerve cell. Axon terminal releases
signalling molecules which carries the message across to the neighbouring
dendrite.
Neuromuscular: a specialised type of chemical synapse where an axon
terminal of a motor neuron contacts a muscle cell.
How are signals transmitted in the nervous system?
The “Soup” versus “Spark” Controversy:
Electrical transmission? – Galvani 1791; Volta 1793;
The Neuromuscular Junction – Kuhne and Krause 1862;
Chemical Transmission? – 1877 Du Bios Reymond;
Nervous System NOT a Syncytium – Cajal; 1888-1934. Prior to this, the
requirement for synaptic signalling was not known: it was thought that the
brain was a single continuous cellular structure (syncytium) with no need
for synaptic transmission. Cajal presented ideas of modern neuroscience
whereby the nervous system has distinct gaps across which information
must be transmitted.
The Synapse – Sherrington 1897 – proposed that this transmission did not
occur via a ‘jump’ of the electrical signal, but through conversion to a
chemical basis across a synapse.
Adrenaline – a released transmitter – Elliot 1897
Otto Loewi – 1921: Proof for the basis of Chemical Transmission:
He proved this by identifying the
very first classical
neurotransmitter. Experiment is
simple but sophisticated: took an
isolated heart in a beaker, and
stimulated the vagus nerve to
, control contraction. Took the buffer/ solution surrounding the stimulated
heart and applied it to heart with removed vagus nerve (no longer
possessing electrical stimulation) and found that he could replicate the
same contraction. Some sort of released factor in the solution due to
stimulation of vagus nerve, which was responsible for controlling heart
contraction. This factor was Vagusstoff (Acetylcholine) – first
demonstration of a classical neurotransmitter in the nervous system.
“The night before Easter Sunday of that year I awoke turned on the light
and jotted down a few notes on a tiny slip of paper. Then I fell asleep
again; it occurred to me that during the night I had written down
something important, but I was unable to decipher the scrawl. The next
night at 3am the idea returned and I headed straight to the lab and had
proved the hypothesis of chemical transmission by 5am” – “Vagusstoff”
– Acetylcholine
Sequence of events:
1. Presynaptic action potential – terminates at nerve terminal
2. Depolarisation of pre-synaptic terminal plasma membrane
3. Release of chemical neurotransmitter from the nerve terminal, which
crosses synaptic cleft
4. Postsynaptic signal stimulated through binding of neurotransmitter to
post-synaptic receptors
The Major Neurotransmitters in the Mammalian Brain:
1. Glutamate – Glutamatergic
Amino acid with an acidic side chain, negatively charged form of alpha-
aminoglutaric acid. It is a constituent of protein, important in cell
metabolism, and also acts an excitatory neurotransmitter in the CNS.
Neuron using glutamate as its primary neurotransmitter = glutamatergic:
neurons are thus defined by their neurochemistry.
2. GABA - GABAergic
Gamma-aminobutyric acid is an inhibitory neurotransmitter that is very
widely distributed in the neurons of the cortex. GABA contributes to motor
control, vision, and many other cortical functions. It also regulates
anxiety.
Neuron using GABA as its neurotransmitter = GABAergic
3. Acetylcholine – Cholinergic
Neurotransmitter secreted by motor neurons that stimulate skeletal
muscle, where it acts as an excitatory transmitter, and by certain neurons
in the PNS and brain.
It acts as an inhibitory transmitter between the vagus nerve and heart
muscle.
Neurons secreting acetylcholine are known as cholinergic.
Acts at several different types of receptor.
4. Noradrenaline – Noradrenergic
Definition: Neurotransmitters are endogenous
chemicals which transmit signals from a neurone to
a target cell across a synapse, a space of usually 20-
40nm.
Communication between many neurones in an
elaborate, complex signalling network is necessary
to coordinate the complex functions of the nervous
system. This is mediated through the hundreds of
thousands of sites of synaptic contacts – dendritic
spines – within a single neuron. A young developing
brain has ~ 100 billion neurones, and so this means
there are 100-500 trillion synapses overall. Such
signalling between many synapses dictates
personality traits, allows coordination of emotions and memory retrieval,
etc.
The molecular events that occur at these individual synapses hence
control the complex functions of the nervous system.
Axodendritic: the classical synaptic contact between an axon terminal of
one nerve cell and a dendrite of another nerve cell. Axon terminal releases
signalling molecules which carries the message across to the neighbouring
dendrite.
Neuromuscular: a specialised type of chemical synapse where an axon
terminal of a motor neuron contacts a muscle cell.
How are signals transmitted in the nervous system?
The “Soup” versus “Spark” Controversy:
Electrical transmission? – Galvani 1791; Volta 1793;
The Neuromuscular Junction – Kuhne and Krause 1862;
Chemical Transmission? – 1877 Du Bios Reymond;
Nervous System NOT a Syncytium – Cajal; 1888-1934. Prior to this, the
requirement for synaptic signalling was not known: it was thought that the
brain was a single continuous cellular structure (syncytium) with no need
for synaptic transmission. Cajal presented ideas of modern neuroscience
whereby the nervous system has distinct gaps across which information
must be transmitted.
The Synapse – Sherrington 1897 – proposed that this transmission did not
occur via a ‘jump’ of the electrical signal, but through conversion to a
chemical basis across a synapse.
Adrenaline – a released transmitter – Elliot 1897
Otto Loewi – 1921: Proof for the basis of Chemical Transmission:
He proved this by identifying the
very first classical
neurotransmitter. Experiment is
simple but sophisticated: took an
isolated heart in a beaker, and
stimulated the vagus nerve to
, control contraction. Took the buffer/ solution surrounding the stimulated
heart and applied it to heart with removed vagus nerve (no longer
possessing electrical stimulation) and found that he could replicate the
same contraction. Some sort of released factor in the solution due to
stimulation of vagus nerve, which was responsible for controlling heart
contraction. This factor was Vagusstoff (Acetylcholine) – first
demonstration of a classical neurotransmitter in the nervous system.
“The night before Easter Sunday of that year I awoke turned on the light
and jotted down a few notes on a tiny slip of paper. Then I fell asleep
again; it occurred to me that during the night I had written down
something important, but I was unable to decipher the scrawl. The next
night at 3am the idea returned and I headed straight to the lab and had
proved the hypothesis of chemical transmission by 5am” – “Vagusstoff”
– Acetylcholine
Sequence of events:
1. Presynaptic action potential – terminates at nerve terminal
2. Depolarisation of pre-synaptic terminal plasma membrane
3. Release of chemical neurotransmitter from the nerve terminal, which
crosses synaptic cleft
4. Postsynaptic signal stimulated through binding of neurotransmitter to
post-synaptic receptors
The Major Neurotransmitters in the Mammalian Brain:
1. Glutamate – Glutamatergic
Amino acid with an acidic side chain, negatively charged form of alpha-
aminoglutaric acid. It is a constituent of protein, important in cell
metabolism, and also acts an excitatory neurotransmitter in the CNS.
Neuron using glutamate as its primary neurotransmitter = glutamatergic:
neurons are thus defined by their neurochemistry.
2. GABA - GABAergic
Gamma-aminobutyric acid is an inhibitory neurotransmitter that is very
widely distributed in the neurons of the cortex. GABA contributes to motor
control, vision, and many other cortical functions. It also regulates
anxiety.
Neuron using GABA as its neurotransmitter = GABAergic
3. Acetylcholine – Cholinergic
Neurotransmitter secreted by motor neurons that stimulate skeletal
muscle, where it acts as an excitatory transmitter, and by certain neurons
in the PNS and brain.
It acts as an inhibitory transmitter between the vagus nerve and heart
muscle.
Neurons secreting acetylcholine are known as cholinergic.
Acts at several different types of receptor.
4. Noradrenaline – Noradrenergic
