Download PS1003(2) Neurones (W)

Introduction to
biological psychology
Topic 2:
Structure and function of neurones
Properties of Neurones
In common with other cells :
• Cell membrane
• Nucleus : containing DNA, the genetic blueprint for the structure
and function of the cell
• Organelles and machinery for translating genetic code into
proteins (Golgi apparatus, endoplasmic reticulum, ribosomes)
• Therefore structural and metabolic proteins (e.g. enzymes)
• Metabolic machinery enabling glucose oxidation to provide
energy
Neuronal Specialisation
Excitability of the membrane
Dendrites – network of fine processes derived from cell body
Synapse – connection between two neurones
Axon hillock – site of action potential generation
Axon – elongated neural process, specialised for rapid
signal transmission over long distances
Myelination – fatty sheath round axon
Membrane potentials
• The neuronal cell membrane is differentially permeable to
intracellular and extracellular chemical constituents.
• Some ions can pass through the membrane easily, others can
pass through, but with difficulty, others cannot pass through at all
• As a result of this differential permeability to ions, there is an
uneven distribution of charge across the membrane
• This difference is the membrane potential:
the resting membrane potential of neurones is around –70mV
• The main ions contributing to the membrane potential are
positively charged sodium (Na+) and potassium (K+), and
negatively charged chloride (Cl-) and proteins (A-).
Membrane potential
Inside
Cell
Outside Cell
K+
AK+
Na+
Cl-
A-
K+
Na+
Cl-
Resting Potential = approx -70 mV
-70mV
Na+
Cl-
Changes in membrane potential
• Incoming signals cause changes in the dendritic membrane potential,
by altering the permeability of the membrane to ions
• Increasing the permeability to sodium (Na+) causes the membrane
potential to become less negative (depolarisation)
• Increasing the permeability to chloride (Cl-) causes the membrane potential
to become more negative (hyperpolarisation)
Inside Cell
AK+
Na +
Na
Cl Cl
+
-
Outside Cell
K+
Na +
Na
Cl Cl
+
-
Signal transmission in dendrites
• Changes in charge diffuse
passively along the membrane
from the point of origin
• Relatively slow
• Decay over distance
+
+
+
+
_
Na+
At any one point the membrane
potential is determined by the
sum of all the individual
depolarising and hyperpolarising
events originating nearby
The axon hillock
Axon hillock - the point where the axon leaves the cell body
• Specialised for the generation of action potentials
• When the net depolarisation at the axon hillock
reaches the threshold potential (around –50mV), an
action potential is generated
Action potential
0
Potential
(mV)
• The action potential
then propagates the
electrical signal
along the axon
-50
-70
Time
No action
potential
Still
no action
potential
The action potential
Potential
(mV)
An electrical ‘spike’ caused by reversal of membrane polarity
• Mediated by rapid changes in membrane permeability to
sodium and potassium
1 m sec
30
• ‘All-or-none’ phenomenon
• an action potential is always the
same size
0
Time
• Does not decay over distance
• an action potential is the same
size when it reaches the terminal as
Refactory
-50
it was when it left the axon hillock.
period
-70
Conduction velocity in axons
A-beta fibre
A-delta fibre
C fibre
400
300
200
100
0
C fibre
Walking
Mile
Sprinter
a-delta
Fast
Greyhound
Cheetah
Motorway
Asian swift
A-beta
Aeroplane
A-alpha
A-alpha fibre
Speed (miles per hour)
Comparison of different classes
of primary afferent axon
500
The synapse
Vesicles containing
neurotransmitter
Neurotransmitter released
into synaptic cleft
Postsynaptic receptors
Neurotransmitter reuptake sites
Neurotransmitters
• Synthesised in the neurones, close to the site of release
• Stored on the terminal until required for release
• Released into synaptic cleft in response to an action potential
• Binds to receptors in post-synaptic membrane
• Causes changes in membrane potential
• Excitatory receptors cause depolarisation
• Inhibitory receptors cause hyperpolarisation
Examples of neurotransmitters
Type
Transmitter
Action
Amino acid
Glutamate
Excitatory (NMDA-type, AMPA-type receptors)
GABA
Inhibitory (A-, and B-type receptors)
Dopamine
Excitatory (D1 & D5 receptors)
Inhibitory (D2, D3 & D4 receptors)
Noradrenaline
Excitatory (subtypes of alpha- & beta-receptors)
Inhibitory (subtypes of alpha- & beta-receptors)
Serotonin
Excitatory (5HT-1, 5HT-2 & 5HT-3 receptors)
Inhibitory (some subtypes of 5HT-1 receptors)
Monoamines
(= 5-hydroxytryptamine = 5HT)
Others
Acetylcholine
Excitatory (muscarinic & some nicotinic receptors)
Inhibitory (subtypes of nicotinic receptors)
Synaptic transmission
Presynaptic neurone
Synaptic cleft
Electrical
Chemical
Action potential
Neurotransmitter
neurotransmitter
neurotransmitter
release
release
Postsynaptic neurone
Electrical
Change in
membrane potential
receptors
Reuptake and/or breakdown
of neurotransmitter
Neurotransmitter-receptor
interaction
Receptor
Neuro
transmitter
AMJ Young, Jan, 2000
C:\0_TEACH\PS103\lec2-sli.ppt
Changes in
membrane
potential
Excitation
or
Inhibition
Receptor pharmacology
Neurotransmitter
Binds to receptor and evokes excitation
or inhibition
Receptor
Neuro
transmitter
Agonist
Binds to receptor and evokes the same
response as the native transmitter.
Receptor
Antagonist
Binds to receptor and does not evoke
any response.
Neuro
Receptor
transmitter
Prevents the native transmitter or any
agonist from binding to the receptor
Excitation
or inhibition
Same action as
native transmitter
No effect
Drugs affecting synaptic transmission
Drugs affecting action potentials
Action potential
Drugs affecting membrane potential
Neurotransmitter
neurotransmitter
release
Change in
membrane potential
receptors
Receptor agonists
and antagonists
Drugs affecting
Synthesis & release
Reuptake and/or breakdown
of neurotransmitter
Drugs affecting reuptake
or breakdown
Actions of therapeutic drugs
Synthesis
Release
NT
Tryptophan
L-DOPA
Amantidine
Receptor
NT
Clearance
NT
Neuroleptics
Anxiolytics
Anticonvulsants
Tricyclic
antidepressants
GABA-t inhibitors
Drugs acting at
neurotransmitter receptors
• Neuroleptics (antipsychotics) – antagonist at dopamine receptors
• Barbiturates and benzodiazapines (anticonvulsants, anxiolylics)
• increase GABA receptor function (allosteric binding site)
• Many plant derivatives
• curare (from frogs) : antagonist at acetylcholine receptors
• atropine (belladonna : from deadly nightshade) : antagonist at
acetylcholine receptors : first pharmacological treatment for
Parkinson’s disease
• nicotine (from tobacco) : agonist at acetylcholine receptors
• muscarine (from fungus) : agonist at acetylcholine receptors
• Many venom toxins
• bungarotoxin (from cobras) : antag at acetylcholine receptors
Drugs affecting membrane potentials
Local anaesthetics
• bind to ion channels in membrane, preventing changes in
membrane potential
Puffer fish venom toxin (tetrodotoxin)
• blocks voltage-dependent sodium channels, therefore blocks
action potentials
Arrow frog venom toxins (batrachotoxin)
• open voltage-dependent sodium channels, therefore “over excite”
neurones
Drugs affecting neurotransmitter
synthesis and storage
Reserpine
• prevents vesicular storage of amine transmitters
L-DOPA
• precursor for dopamine – increases dopamine concentrations:
main therapeutic agent used in Parkinson’s disease
Tryptophan
• precursor for serotonin : effective in treating some depression
Drugs affecting neurotransmitter release
Botulinum toxin
• Prevents acetylcholine release at neuromuscular junction (NMJ)
Black widow venom toxin
• increases then eliminates acetylcholine release at NMJ
? Amantidine ?
• Mechanism uncertain, but may increase dopamine
release: used in the treatment of Parkinson’s disease
Drugs affecting reuptake and
breakdown of neurotransmitters
Monoamine reuptake inhibitors
• tricyclic antidepressants : prevents reuptake of noradrenaline and
serotonin
• fluoxitine (Prozac) : prevents reuptake of serotonin
Monoamine oxidase inhibitors
• prevent the breakdown of amine neurotransmitters
• Selegiline (deprynil) : blocks dopamine breakdown: used in the
treatment of Parkinson’s disease
• Phenelzine : blocks breakdown of noradrenaline and serotonin:
antidepressant
GABA transaminase (GABA-t) inhibitors
• prevent the breakdown of GABA : anticonvulsant
Amphetamine and cocaine
• Increase dopamine levels by blocking reuptake: amphetamine also increases
dopamine release and blocks monoamine oxidase