Neurotransmitter
Function
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Outline
 A few definitions
 Neuronal structure
 Communication within a neuron: The Action
Potential
 Communication between neurons:
Neurotransmission
 Types of Neurotransmitters, Agonists and
Antagonists
 Types of Receptors
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A few definitions
 Amino acid = A class of organic molecules
containing an amino group (-NH2).
 Peptide = A chain of two or more amino acids,
smaller than proteins.
 Protein = A long chain of amino acids which
contain carbon, hydrogen, oxygen, nitrogen and
usually sulphur.
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A few definitions
 Neurotransmitter = A substances released from
the axon terminal of a neuron and binds to the
receptor.
 Enzyme = Protein that controls a chemical
reaction, combining or dividing a substance
 Ions = An electrically charged particle
• positive or negative
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Neuronal Structure
 Dendrites receive incoming information from
other neurons
 Makes up most of the surface area of the neuron
 Dendritic spines can number in the thousands
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Neuronal Structure
The soma:
 processes this information,
 maintains integrity of neuronal processes
 allows for transmission of neuronal information
(action potential)
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Neuronal Structure
 The axon transmits information to other neurons
 A single axon with branching “collaterals”, but is
always a single channel/message.
 Teledendria: end branches of axon
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Neuronal Structure
Soma
Axon
Dendrites
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Neuronal Structure
 Terminal button or bouton usually near
dendritic spine of another neuron (but no
touching!)
 The terminal button converts action potentials
into the release of neurotransmitter.
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At the terminal button
 Information is carried by a chemical-electrical
process
 Whether there is a release of transmitter is
dependent on information from efferent neurons
 If transmitter is released into synaptic cleft, it will
bind to the appropriate receptors located on the
dendritic spines
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Communication Within Neurons
 A single action potential is usually not enough to
release transmitter
 There has to be repeated presentation of action
potentials for neuronal conduction to occur
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Communication Within Neurons
 A membrane of a neuron that is inactive is
electrically charged--a resting potential.
 This potential is about -70mV.
 The potential fluctuates depending on the flow and
concentration of ions inside and outside the cell.
• depolarized or hyperpolarized
 Gated channels regulated by receptors control the
flow of ions.
 Once the potential depolarizes to a particular level,
an action potential occurs.
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Communication Within Neurons
Why is there a resting potential at all?
1. The flow of ions is mediated by the structure of
the cell membrane
 Some ions are free to pass though the membrane
at any time, others (Na+) are not.
 Concentration gradient (Diffusion): Ions will
travel (if they can) from an area of high
concentration to one of low concentration.
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Communication Within Neurons
Why is there a resting potential at all?
2. The flow of ions is also dependent on the relative
potentials inside and outside the cell.
 Electrostatic pressure (voltage gradient):
Positively charged ions attracted to a negative
charge, and vice versa.
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Communication Within Neurons
 Because the membrane is selectively permeable,
the concentration and voltage gradients interact
to produce a negative resting potential inside the
cell.
 The resting potential is also maintained by the
sodium-potassium pump.
• Pumps Na+ out and K+ in.
 Ions remain close to the cell membrane and
influence the membrane potential.
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Communication Within Neurons
Extra-cellular space:
Intra-cellular space:
Potassium (K+)
Anions (A-)
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Sodium (Na+)
Cloride (Cl-)
Calcium (Ca++)
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Communication Within Neurons
 When potential depolarizes to -50mV, voltage
gated channels are opened for Na+ and K+
 There is an influx of Na+ and an efflux of K+
 These ions move outside of their area of usual
concentration
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Communication Within Neurons
 The opening of channels brings membrane
potential to +30mV.
 Once the action potential has reached its peak,
gated channels close, and begins its return to a
resting state.
 Extra K+ ions outside the membrane are
responsible for a brief hyperpolarization prior to
the resting state.
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Communication Within Neurons
 The action potential is a local (usually dendritic)
event
 Potential is propagated across the membrane
(120meters/second).
 Parts of the axon covered by the myelin sheath
cannot produce action potentials.
 The potential can jump along the length of the
axon by Nodes of Ranvier via passive conduction
(cable properties).
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Communication Within Neurons
 Once enough action potentials reach the terminal
button, transmitter is released.
 Ca++ (calcium) channels open in the membrane
 Ca++ enters and fuses with the synaptic vesicles
that are docked to the membrane
 Vesicles then release neurotransmitter into the
synaptic cleft
 Neurotransmitter crosses the cleft and binds to
the receptors of the postsynaptic neuron
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Communication Within Neurons
Axonal conduction obeys two laws:
 All or None Law – once triggered, an action
potential is transmitted down to the terminal
button.
 Rate Law – The number of action potentials
produced by a neuron determines how strong
activation of other neurons will be.
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Activation of Receptors
 A receptor is linked to to the opening or closing
of an ion channel.
 Receptor is activated once a neurotransmitter
binds to it.
 The membrane potential changes:
• Excitatory – depolarizes the cell
• Inhibitory – hyperpolarizes the cell
 The change in potential is determined by the
receptor, not the neurotransmitter
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Activation of Receptors
 Excitatory Postsynaptic Potential (EPSP) – due to
opening of Na+ channels
 Inhibitory Postsynaptic Potential (IPSP) – due to
opening of K+ channels
 Postsynaptic potentials are brief due to:
• Reuptake
• Enzymatic deactivation
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Reuptake
 Extremely rapid removal of neurotransmitter
from the synaptic cleft by the terminal button
 Presynaptic transporter molecules pick up the
neurotransmitter
 Some neurotransmitters are reabsorbed by
support cells (astrocytes)
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Enzymatic Deactivation
 Only occurs for acetylcholine (ACh)
 An enzyme, acetylcholinesterase, is found in the
postsynaptic membrane of neurons in the ACh
pathways of the brain
 This enzyme breaks ACh into its inactive
constituents – acetate and choline
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Summation
 EPSPs increase the likelihood that a neuron fires
 IPSPs decreases this likelihood
 Neural integration: Rate at which an axon fires
determined by relative activity of EPSPs and
IPSPs
 Result is either neural activation or inhibition (not
the same as behavioural activation or inhibition)
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Communication Between Neurons
Three types of chemicals:
 Neurotransmitters – synthesized within the
axon, travel short distances, fast acting
 Neuromodulators – synthesized within the
soma, travel farther distances (diffusion), slower
• Peptides
 Neurohormones – synthesized in endocrine
glands, also travel far distances
• Bind to receptors on the cell or nuclear membrane
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Neurotransmitter Agonists
 Neurotransmitter action can be mimicked by
drugs that are similar in chemical structure
 Agonist binds directly to receptors
 Indirectly increase the production of
neurotransmitter
 Example: L-DOPA – increases concentration of DA
in the substantia nigra and alleviates symptoms
of Parkinson’s disease
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Neurotransmitter Antagonists
 Antagonists oppose or inhibit
 It may block binding of the neurotransmitter to
its receptor
 It may prevent reuptake and recycling
 Indirectly decrease production
 Example: Clozapine blocks DA receptors – used
to treat symptoms of schizophrenia (cortical
components)
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Amino Acids
 Some amino acids don’t need to be converted to
have an action on synapses
1. Glutamate
2. GABA (-amino-butyric acid)
3. Glycine
 Most synaptic communication is accomplished by
amino acids
 Fast acting over short distances
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Glutamate
 Main excitatory neurotransmitter of the CNS
 Found in all CNS structures
 Involved in almost all brain functions
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GABA
 Inhibition of neurons
 Control effects of over-excitation – which can
lead to seizures
 Found in all CNS structures
 Involved in almost all brain functions
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Glycine
 Inhibitory: Seems to be secreted by neurons in
the lower brain stem at the same time as GABA
 Not sure of differences from GABA
 No known agonists
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Monoamines

1.
2.
3.
Catecholamines
Dopamine
Norepinephrine
Epinephrine (sort of)
 Serotonin
 Cell bodies producing these are found primarily
in the brain stem and branch profusely
 Widespread areas of effect
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Dopamine
 Produces both EPSPs and IPSPs depending on the
postsynaptic receptor
 Implicated in movement, attention, learning and
addiction
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Dopamine
Main DA systems:
1. Nigrostriatal (Movement – damage causes Parkinson’s
Disease)
• Cell bodies located in substantia nigra
• Project to caudate nucleus and putamen
2. Mesolimbic (Reward system)
• Cell bodies in ventral tegmental area
• Project to nucleus accumbens (prefrontal subcortex),
amygdala, and hippocampus
3. Mesocortical (STM, planning, strategy preparation)
• Cell bodies in ventral tegmental area
• Project to prefrontal cortex
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Norepinephrine
 Sythesized from DA
 Cell bodies of most NE neurons are located in
regions of the pons and medulla and the
thalamus
 NE receptors are excitatory and inhibitory
 Locus coeruleus in the pons – activation leads to
increased vigilance
 Arousal: sexual behaviour and food
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Serotonin
 5-hydroxytryptamine (5-HT)
 Cell bodies are found in raphe nucleus, pons, and
medulla (part of the reticular formation)
 Projections are mainly to the cerebral cortex, the
hippocampus, and basal ganglia
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Serotonin
 Plays a role in many behaviours:
• Regulation of mood
• Control of eating, sleep, arousal
• Regulation of pain
 Involved in higher cognition and emotion
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Acetylcholine
 Excitatory
 Distribution throughout brain
 Three areas of importance:
• Dorsolateral pons – involved in REM sleep
• Basal forebrain – perceptual learning
• Medial septum – modulation of hippocampus and
formation of memories
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Neuromodulators: Peptides
 Endogenous opioids: analgesic properties
•
•
•
•
Endorphins, enkephalins, and dynorphins
Regulation of pain for different brain areas
Enhancement of fight or flight response
Linked to memory: hippocampus and amygdala
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Neuromodulators:
Lipids and Nucleosides
 Lipids: fat-like substance, water insoluable
• Cannabis: THC (tetrahydrocannabinol) and anandamide
(neuronal equivalent)
 Nucleosides: Sugar molecule bound with one of
two amino acids (purine or pyrimidine)
• Adenosine: dilation of blood vessels, especially during
sleep
• Caffeine: adenosine antagonist producing headaches,
drowsiness, and difficulty concentrating
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Neurohormones
 Not produced in the brain
 Many work in multiple organ systems
• Cholecystokinin, Neuropeptide Y, Substance P, Thyroid
hormone releasing hormone (TRH), etc.
 Typically used in brain areas that control these
organs
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Activation of Receptors
•
•
A chemical may bind to more than one type of
receptor
Different receptors accomplish different
functions
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Activation of Receptors
1. Ionotropic receptor: contains a binding site and
and ion channel
• Binding of neurotransmitter directly opens
channel
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Activation of Receptors
2. Metabotopic receptor: contains binding site for
neurotransmitter.
• Activates an enzyme that begins a series of
events that opens up a channel
• Release of a G-protein that is coupled to the
receptor
• Second messenger: G-proteins convey messages
to other molecules that in turn produce other
activating chemicals.
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Agonists and Antagonists
 GABA agonists (mimic GABA at receptor sites):
• Muscimol – used to dilate pupils
• Benzodiazepines – used to treat anxiety
• Barbiturates – used as an anesthetic and to treat
seizures in children under the age of 2 (controversy)
• Steroids – particularly those used for anesthesia
• Alcohol
 GABA antagonists (block receptors):
• Bicuculline – induces convulsions
• Picrotoxin – induces convulsions
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Glycine Agonists
 No known agonists
 Antagonists:
• Bacterium that causes tetanus – prevents release of
glycine and leads to constant contraction of muscles
• Strychnine – causes convulsions and death – not sure
what its function is in terms of glycine
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Agonists and Antagonists
 5-HT agonists:
• Fenfluramine – stimulates release of 5-HT – used to
treat eating disorders and depression
• Fluoxetine – inhibits reuptake of 5-HT – used to treat
eating disorders and depression
 5-HT antagonists:
• Reserpine – inhibit storage of 5-HT in synaptic vesicles –
used to normalize mood states
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Agonists and Antagonists
 NE agonists:
• Phenylephrine
• Clonidine
• Desipramine
 All involved in increasing vigilance (sometimes used
to treat mood disorders, eating disorders) through
decreased activity of MAO
 NE antagonists:
• Reserpine
• Atenolol
 Used to treat hallucinations and delusions and
sometimes used to treat mania
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Agonists and Antagonists
 Glutamate agonists:
•
•
•
•
AMPA
NMDA
Kainate
All stimulate their namesake receptors and increase
excitation
• Behavioural effects vary depending on neural integration
and the nature of the neurons activated
• In high doses, all induce seizures
 Glutamate antagonists:
• PCP
• Ecstasy
• Can lead to memory loss, inebriation, apathy
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Agonists and Antagonists
 Drugs that facilitate ACh action (agonists):
• Black widow spider venom – results in overactivity of
ACh which leads to seizures
• Nicotine – in small doses has been found to improve
perceptual learning
• Muscarine – found in Amanita mushrooms - similar
effects to spider venom
• Neostigmine – used to treat low ACh levels in those with
myasthenia gravis which results from destruction of ACh
receptors on muscles
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Agonists and Antagonists
 ACh antagonists (all cause paralysis) :
•
•
•
•
Botulinum toxin – prevents release of ACh
Curare – blocks ACh receptors
Atropine – blocks ACh receptors
Hemicholinium – prevents recycling of choline and
reduces production of ACh
• Some of these are used medically in surgery
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Agonists and Antagonists
 DA agonists:
• L-DOPA – increases concentration of DA in the
•
•
•
•
•
substantia nigra and alleviates symptoms of PD
Dihydrexidine – used to treat movement disorders
Bromocriptine – used to treat movement disorders
Cocaine – increases attention and awareness
Methylphenidate – increases attention and awareness
Deprenyl – prevents destruction of DA – used to treat
pain
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Agonists and Antagonists
 DA antagonists:
• AMPT – used to block synthesis of DA – only used in
experimental research on animals
• Reserpine – keeps DA from entering synaptic vesicles –
used in herbal medicine and used to be used to treat
high blood pressure and stress (side effects)
• Clozapine – block DA receptors – used to treat
symptoms of schizophrenia
• Chlorpromazine - block DA receptors – used to treat
symptoms of schizophrenia
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