Transcript Neurotransmitter Function

Neurotransmitter
Function
PSY4080 6.0D
Neurotransmitter Function
1
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
PSY4080 6.0D
Neurotransmitter Function
2
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.
PSY4080 6.0D
Neurotransmitter Function
3
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
PSY4080 6.0D
Neurotransmitter Function
4
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
PSY4080 6.0D
Neurotransmitter Function
5
Neuronal Structure
The soma:
 processes this information,
 maintains integrity of neuronal processes
 allows for transmission of neuronal information
(action potential)
PSY4080 6.0D
Neurotransmitter Function
6
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
PSY4080 6.0D
Neurotransmitter Function
7
Neuronal Structure
Soma
Axon
Dendrites
PSY4080 6.0D
Neurotransmitter Function
8
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.
PSY4080 6.0D
Neurotransmitter Function
9
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
PSY4080 6.0D
Neurotransmitter Function
10
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
PSY4080 6.0D
Neurotransmitter Function
11
PSY4080 6.0D
Neurotransmitter Function
12
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.
PSY4080 6.0D
Neurotransmitter Function
13
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.
PSY4080 6.0D
Neurotransmitter Function
14
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.
PSY4080 6.0D
Neurotransmitter Function
15
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.
PSY4080 6.0D
Neurotransmitter Function
16
Communication Within Neurons
Extra-cellular space:
Intra-cellular space:
Potassium (K+)
Anions (A-)
PSY4080 6.0D
Sodium (Na+)
Cloride (Cl-)
Calcium (Ca++)
Neurotransmitter Function
17
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
PSY4080 6.0D
Neurotransmitter Function
18
PSY4080 6.0D
Neurotransmitter Function
19
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.
PSY4080 6.0D
Neurotransmitter Function
20
PSY4080 6.0D
Neurotransmitter Function
21
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).
PSY4080 6.0D
Neurotransmitter Function
22
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
PSY4080 6.0D
Neurotransmitter Function
23
PSY4080 6.0D
Neurotransmitter Function
24
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.
PSY4080 6.0D
Neurotransmitter Function
25
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
PSY4080 6.0D
Neurotransmitter Function
26
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
PSY4080 6.0D
Neurotransmitter Function
27
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)
PSY4080 6.0D
Neurotransmitter Function
28
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
PSY4080 6.0D
Neurotransmitter Function
29
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)
PSY4080 6.0D
Neurotransmitter Function
30
PSY4080 6.0D
Neurotransmitter Function
31
PSY4080 6.0D
Neurotransmitter Function
32
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
PSY4080 6.0D
Neurotransmitter Function
33
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
PSY4080 6.0D
Neurotransmitter Function
34
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)
PSY4080 6.0D
Neurotransmitter Function
35
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
PSY4080 6.0D
Neurotransmitter Function
36
Glutamate
 Main excitatory neurotransmitter of the CNS
 Found in all CNS structures
 Involved in almost all brain functions
PSY4080 6.0D
Neurotransmitter Function
37
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
PSY4080 6.0D
Neurotransmitter Function
38
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
PSY4080 6.0D
Neurotransmitter Function
39
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
PSY4080 6.0D
Neurotransmitter Function
40
Dopamine
 Produces both EPSPs and IPSPs depending on the
postsynaptic receptor
 Implicated in movement, attention, learning and
addiction
PSY4080 6.0D
Neurotransmitter Function
41
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
PSY4080 6.0D
Neurotransmitter Function
42
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
PSY4080 6.0D
Neurotransmitter Function
43
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
PSY4080 6.0D
Neurotransmitter Function
44
Serotonin
 Plays a role in many behaviours:
• Regulation of mood
• Control of eating, sleep, arousal
• Regulation of pain
 Involved in higher cognition and emotion
PSY4080 6.0D
Neurotransmitter Function
45
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
PSY4080 6.0D
Neurotransmitter Function
46
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
PSY4080 6.0D
Neurotransmitter Function
47
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
PSY4080 6.0D
Neurotransmitter Function
48
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
PSY4080 6.0D
Neurotransmitter Function
49
Activation of Receptors
•
•
A chemical may bind to more than one type of
receptor
Different receptors accomplish different
functions
PSY4080 6.0D
Neurotransmitter Function
50
Activation of Receptors
1. Ionotropic receptor: contains a binding site and
and ion channel
• Binding of neurotransmitter directly opens
channel
PSY4080 6.0D
Neurotransmitter Function
51
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.
PSY4080 6.0D
Neurotransmitter Function
52
PSY4080 6.0D
Neurotransmitter Function
53
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
PSY4080 6.0D
Neurotransmitter Function
54
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
PSY4080 6.0D
Neurotransmitter Function
55
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
PSY4080 6.0D
Neurotransmitter Function
56
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
PSY4080 6.0D
Neurotransmitter Function
57
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
PSY4080 6.0D
Neurotransmitter Function
58
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
PSY4080 6.0D
Neurotransmitter Function
59
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
PSY4080 6.0D
Neurotransmitter Function
60
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
PSY4080 6.0D
Neurotransmitter Function
61
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
PSY4080 6.0D
Neurotransmitter Function
62