2. Synaptic Transmission Syllabus 3.5.2 Toole page 174-179

3. Aims: 1.Label the following structures: –Synapse –Neuromuscular junction 2.Explain the sequence of events involved in transmission across a cholinergic synapse and across a neuromuscular junction. 3.Explain the following terms: –Unidirectionality –Temporal & spatial summation –Inhibition 4.Describe the effects of drugs on a synapse.

4. The structure of the synapse & neuromuscular junction. Read the comprehension and label the following diagram and determine the role / function of each structure.

5. The structure of the synapse A.Neuron (Presynaptic) B.Neuron (Postsynaptic) 1.Mitochondria 2.Synaptic vesicle full of neurotransmitter 3.Autoreceptor 4.Synaptic cleft 5.Neurotransmitter receptor 6.Calcium Channel 7.Fused vesicle releasing neurotransmitter 8.Neurotransmitter re-uptake pump

6. The structure of a neuromuscular junction. 1.Presynaptic terminal motor neurone 2.Postsynaptic muscle membrane (Sarcolemma) 3.Synaptic vesicle 4.Receptor 5.Mitochondria

7. A cholinergic synapse These types of synapse are common in vertebrates. They occur in the CNS and at neuromuscular junctions. In cholinergic synapse the neurotransmitter is acetylcholine. Acetylcholine is made up of two parts: 1.Acetyl (ethanoic acid) 2.Choline

10. What happens at a cholinergic synapse? Stage 1 An action potential arrives at presynaptic membrane. Voltage gated calcium channels in the presynaptic membrane open. Calcium ions enter the presynaptic neurone.

11. What happens at a cholinergic synapse? Stage 2 Calcium ions cause synaptic vesicles to fuse with the presynaptic membrane. The neurotransmitter acetylcholine is released into the synaptic cleft.

12. What happens at a cholinergic synapse? Stage 3 Acetylcholine diffuses across the synaptic cleft. It binds to specific receptor sites on the sodium ion channel in the postsynaptic neurone membrane.

13. What happens at a cholinergic synapse? Stage 4 Sodium channels open. Sodium ions diffuse into the postsynaptic membrane causing depolarisation. This may initiate an action potential.

14. What happens at a cholinergic synapse? Stage 5 Acetylcholinesterase breaks down acetylcholine into choline and ethanoic acid. The removal of acetylcholine from the receptors cause sodium ion channels to close in the membrane of the postsynaptic neurone. The products diffuse back across the synaptic cleft into the presynaptic neurone.

15. What happens at a cholinergic synapse? Stage 6 ATP released by the mitochondria is used to recombine choline and ethanoic acid into acetylcholine. This is stored in vesicles for future use.

16. Transmission across a synapse 1.When an impulse arrives at a synaptic knob it causes calcium ion channels to open. 2.This results in calcium ions diffusing into it from the surrounding fluid. 3.The calcium ions cause some of the synaptic vesicles to move towards the presynaptic membrane. 4.The vesicles fuse to the presynaptic membrane and discharge a neurotransmitter (acetylcholine) into the synaptic cleft. 5.The neurotransmitter (acetylcholine) diffuses across the cleft to the postsynaptic membrane. 6.The neurotransmitter binds to receptor sites on the sodium ion channel in the membrane of the postsynaptic neurone. 7.This causes the sodium ion channels to open and sodium ions enter the post synaptic neurone diffusing rapidly along a concentration gradient. 8.The influx of sodium ions generates a new action potential in the postsynaptic neurone. 9.Acetylcholinesterase hydrolyses acetylcholine into choline and ethanoic acid, which diffuses back across the synaptic cleft into the presynaptic neurone. 10.Sodium ion channels close in the absence of acetylcholine in the receptor sites. 11.ATP released by mitochondria is used to recombine choline and ethanoic acid into acetylcholine.

17. Same stages as cholinergic synapses, however, the postsynaptic membrane is the muscle fibre membrane (Sarcolemma). Depolarisation of the sarcolemma leads to contraction of muscle fibre.

18. Features of synapses 1.Unidirectionality –Synapses can only pass impulses in one direction, from the presynaptic neurone to the postsynaptic neurone. 2.Summation –Low frequency action potentials often produce insufficient amounts of neurotransmitter to trigger a new action potential in the postsynaptic neurone. They, can be made to do so by a process called summation where neurotransmitter builds up in the synapse by one of two methods: a)Spatial summation ~ Many different presynaptic neurones release neurotransmitter. b)Temporal summation ~ A single presynaptic neurones releases neurotransmitter many times over a short period. 3.Inhibition –On the postsynaptic membrane of some synapses, the protein channels carrying chloride ions can be made to open. Thus leads to an influx of chloride ions, making the inside of the postsynaptic membrane even more negative than when it is at resting potential.

19. Neurotransmitters There are dozens of different neurotransmitters in the neurons of the body. Neurotransmitters can be either excitatory or inhibitory. Each neuron generally synthesises and releases a single type of neurotransmitter. The major neurotransmitters are indicated on the next slide.

20. Major Neurotransmitters in the Body NeurotransmitterRole in the Body AcetylcholineA neurotransmitter used by the spinal cord neurons to control muscles and by many neurons in the brain to regulate memory. In most instances, acetylcholine is excitatory. DopamineThe neurotransmitter that produces feelings of pleasure when released by the brain reward system. Dopamine has multiple functions depending on where in the brain it acts. It is usually inhibitory. GABA (gamma-aminobutyric acid) The major inhibitory neurotransmitter in the brain. GlutamateThe most common excitatory neurotransmitter in the brain. GlycineA neurotransmitter used mainly by neurons in the spinal cord. It probably always acts as an inhibitory neurotransmitter. NorepinephrineNorepinephrine acts as a neurotransmitter and a hormone. In the peripheral nervous system, it is part of the flight-or-flight response. In the brain, it acts as a neurotransmitter regulating normal brain processes. Norepinephrine is usually excitatory, but is inhibitory in a few brain areas. SerotoninA neurotransmitter involved in many functions including mood, appetite, and sensory perception. In the spinal cord, serotonin is inhibitory in pain pathways.

21. Drugs Drugs which have molecules of similar shape to transmitter substances can affect protein receptors in postsynaptic membranes. Drugs that stimulate a nervous system are called AGONISTS. Drugs that inhibit a nervous system are called ANTAGONISTS.

22. Drugs Interfere with Neurotransmission Drugs can affect synapses at a variety of sites and in a variety of ways, including: 1.Increasing number of impulses 2.Release neurotransmitter from vesicles with or without impulses 3.Block reuptake or block receptors 4.Produce more or less neurotransmitter 5.Prevent vesicles from releasing neurotransmitter

23. Drugs That Influence Neurotransmitters Change in NeurotransmissionEffect on Neurotransmitter release or availability Drug that acts this way increase the number of impulsesincreased neurotransmitter releasenicotine, alcohol, opiates release neurotransmitter from vesicles with or without impulses increased neurotransmitter release amphetamines methamphetamines release more neurotransmitter in response to an impulse increased neurotransmitter release nicotine block reuptakemore neurotransmitter present in synaptic cleft cocaine amphetamine produce less neurotransmitterless neurotransmitter in synaptic cleft probably does not work this way prevent vesicles from releasing neurotransmitter less neurotransmitter releasedNo drug example block receptor with another molecule no change in the amount of neurotransmitter released, or neurotransmitter cannot bind to its receptor on postsynaptic neuron LSD caffeine

24. Homework In groups of 3 you will produce a leaflet that consists of 3 typed A4 information sheets. Each information sheet should provide information to explain how the following neurotransmitters effect the body: 1.Endorphins 2.Serotonin 3.Gamma aminobutyric acid (GABA) The information sheet should also explain how drugs can effect the role of each specific neurotransmitter. It is essential that diagrams of presynaptic neurones, postsynaptic neurones and receptor sites are included to enhance the detail of the information sheet.