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 – elongated neural process, specialised for rapid signal transmission over long distances

Myelination – fatty sheath round axon

Axon hillock – site of action potential generation

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

A-

K+

Na+

Cl-

-70mV

Inside Cell

A-

K+

Cl-

Na+

K+

Cl-

Na+

Outside Cell

Resting Potential = approx -70 mV

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 chloride (Cl-) causes the membrane potential to become more negative (hyperpolarisation)

• Increasing the permeability to sodium (Na+) causes the membrane potential to become less negative (depolarisation)

Inside Cell

A-

K+

Cl-

Na+

K+

Cl-

Na+

Outside Cell

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

At any one point the membrane potential is determined by the sum of all the individual depolarising and hyperpolarising events originating nearby

Na+

+ + + +_

• The action potential then propagates the electrical signal along the axon

Pot

enti

al(m

V)

0

-50

-70

Time

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

No action potentialStill no action potential

Action potential

Pot

enti

al(m

V)

0

-50

-70

Time

30

The action potential

• ‘All-or-none’ phenomenon • an action potential is always the same size

• Does not decay over distance• an action potential is the same size when it reaches the terminal as it was when it left the axon hillock.

An electrical ‘spike’ caused by reversal of membrane polarity

• Mediated by rapid changes in membrane permeability to sodium and potassium

1 m sec

Refactory period

Conduction velocity in axons

Comparison of different classes of primary afferent axon

A-alpha fibre

A-beta fibre

A-delta fibre

C fibre 0

100

200

300

400

500

C fib

reW

alkin

gM

ileSp

rinter

a-de

lta Fast

Grey

houn

dCh

eetah

Mot

orwa

yAs

ian sw

iftA-

beta

Aero

plan

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alpha

Spee

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hou

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The synapse

Vesicles containing neurotransmitter

Postsynaptic receptors

Neurotransmitter reuptake sites

Neurotransmitter released into synaptic cleft

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)

Monoamines 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) (= 5-hydroxytryptamine = 5HT) Inhibitory (some subtypes of 5HT-1 receptors)

Others Acetylcholine Excitatory (muscarinic & some nicotinic receptors)Inhibitory (subtypes of nicotinic receptors)

Synaptic transmission

Presynaptic neurone Synaptic cleft Postsynaptic neurone

neurotransmitterrelease

receptors

Chemical

Neurotransmitter

Electrical

Action potential

Electrical

Change in membrane potential

neurotransmitterrelease

receptorsreceptors

Reuptake and/or breakdownof neurotransmitter

receptors

Neurotransmitter-receptor interaction

Excitationor

Inhibition

Neurotransmitter

Receptor

AMJ Young, Jan, 2000C:\0_TEACH\PS103\lec2-sli.ppt

Changes in membrane potential

Receptor pharmacology

Neurotransmitter

Receptor

Excitationor inhibition

Neurotransmitter

Receptor

No effect

Receptor

Same action asnative transmitter

NeurotransmitterBinds to receptor and evokes excitation or inhibition

AgonistBinds to receptor and evokes the same response as the native transmitter.

AntagonistBinds to receptor and does not evoke any response.

Prevents the native transmitter or any agonist from binding to the receptor

Action potential Neurotransmitter Change in membrane potential

Reuptake and/or breakdownof neurotransmitter

Drugs affecting synaptic transmission

neurotransmitterrelease

receptors

Drugs affecting action potentials

Receptor agonistsand antagonists

Drugs affecting Synthesis & release

Drugs affecting reuptakeor breakdown

Drugs affecting membrane potentialDrugs affecting action potentials

Receptor agonistsand antagonists

Drugs affecting Synthesis & release

Drugs affecting reuptakeor breakdown

Drugs affecting membrane potential

Actions of therapeutic drugs

Synthesis Release Receptor Clearance

NT NT NT

TryptophanL-DOPA

Amantidine NeurolepticsAnxiolyticsAnticonvulsants

Tricyclic antidepressantsGABA-t inhibitors

Drugs acting atneurotransmitter receptors

• Many venom toxins• bungarotoxin (from cobras) : antag at acetylcholine 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

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

Black widow venom toxin• increases then eliminates acetylcholine release at NMJ

Botulinum toxin• Prevents acetylcholine release at neuromuscular junction (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

Amphetamine and cocaine• Increase dopamine levels by blocking reuptake: amphetamine also increases dopamine release and blocks monoamine oxidase

GABA transaminase (GABA-t) inhibitors• prevent the breakdown of GABA : anticonvulsant