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 – elongated neural process, specialised for rapid signal transmission over long distances Myelination – fatty sheath round axon Axon hillock – site of action potential generation

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

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

7. 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+ + + + + _

8. The action potential then propagates the electrical signal along the axon Potential (mV) 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 potential Still no action potential Action potential

9. Potential (mV) 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

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

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

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 acidGlutamateExcitatory (NMDA-type, AMPA-type receptors) GABAInhibitory (A-, and B-type receptors) MonoaminesDopamineExcitatory (D1 & D5 receptors) Inhibitory (D2, D3 & D4 receptors) NoradrenalineExcitatory (subtypes of alpha- & beta-receptors) Inhibitory (subtypes of alpha- & beta-receptors) SerotoninExcitatory (5HT-1, 5HT-2 & 5HT-3 receptors) (= 5-hydroxytryptamine = 5HT) Inhibitory (some subtypes of 5HT-1 receptors) OthersAcetylcholineExcitatory (muscarinic & some nicotinic receptors) Inhibitory (subtypes of nicotinic receptors)

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

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

16. Receptor pharmacology Neuro transmitter Receptor Excitation or inhibition Neuro transmitter Receptor No effect Receptor Same action as native transmitter 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. Action potentialNeurotransmitterChange in membrane potential Reuptake and/or breakdown of neurotransmitter Drugs affecting synaptic transmission neurotransmitter release receptors Drugs affecting action potentials Receptor agonists and antagonists Drugs affecting Synthesis & release Drugs affecting reuptake or breakdown Drugs affecting membrane potential Drugs affecting action potentials Receptor agonists and antagonists Drugs affecting Synthesis & release Drugs affecting reuptake or breakdown Drugs affecting membrane potential

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

19. Drugs acting at neurotransmitter 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

20. 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

21. 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

22. 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

23. 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