Introduction to biological psychology

1. Introduction to biological psychology Topic 2: Structure and function of neurones

2. 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

3. 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

4. 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-).

5. K+ Na+ A- Cl- -70mV Membrane potential Outside Cell Inside Cell A- K+ K+ Na+ Na+ Cl- Cl- Resting Potential = approx -70 mV

6. Cl- Na+ 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 Outside Cell A- K+ K+ Na+ Na+ Cl- Cl-

7. _ + + + + Signal transmission in dendrites Na+ • 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

8. Action potential 0 Time Potential (mV) -50 -70 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 • The action potential then propagates the electrical signal along the axon No action potential Still no action potential

9. 1 m sec 30 0 Time Potential (mV) Refactory period -50 -70 The action potential • An electrical ‘spike’ caused by reversal of membrane polarity • Mediated by rapid changes in membrane permeability to sodium and potassium • ‘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.

10. Speed (miles per hour) Conduction velocity in axons Comparison of different classes of primary afferent axon A-alpha fibre A-beta fibre A-delta fibre C fibre

11. The synapse Vesicles containing neurotransmitter Neurotransmitter released into synaptic cleft Postsynaptic receptors Neurotransmitter reuptake sites

12. 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

13. Examples of neurotransmitters TypeTransmitterAction 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)

14. receptors Reuptake and/or breakdown of neurotransmitter Synaptic transmission Presynaptic neurone Synaptic cleft Postsynaptic neurone Chemical Neurotransmitter Electrical Action potential ElectricalChange in membrane potential neurotransmitter release neurotransmitter release receptors receptors receptors

15. Neurotransmitter Neurotransmitter-receptor interaction Receptor Excitation or Inhibition Changes in membrane potential AMJ Young, Jan, 2000 C:\0_TEACH\PS103\lec2-sli.ppt

16. Receptor Excitation or inhibition Neurotransmitter Neurotransmitter Receptor Same action as native transmitter Receptor No effect Receptor pharmacology Neurotransmitter Binds to receptor and evokes excitation or inhibition Agonist Binds to receptor and evokes the same response as the native transmitter. Antagonist Binds to receptor and does not evoke any response. Prevents the native transmitter or any agonist from binding to the receptor

17. Drugs affecting membrane potential Drugs affecting membrane potential Drugs affecting action potentials Drugs affecting action potentials Receptor agonists and antagonists Receptor agonists and antagonists Drugs affecting reuptake or breakdown Drugs affecting reuptake or breakdown Drugs affecting Synthesis & release Drugs affecting Synthesis & release Drugs affecting synaptic transmission Action potential Neurotransmitter Change in membrane potential Reuptake and/or breakdown of neurotransmitter neurotransmitter release receptors

18. Synthesis Release Receptor Clearance NT NT NT Tricyclic antidepressants GABA-t inhibitors Neuroleptics Anxiolytics Anticonvulsants Tryptophan L-DOPA Amantidine Actions of therapeutic drugs

19. 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 acting atneurotransmitter receptors

20. 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 membrane potentials

21. 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 synthesis and storage

22. 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 neurotransmitter release

23. 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 Drugs affecting reuptake and breakdown of neurotransmitters