Learning Objectives What is a synapse? Explain the role of calcium ions Explain the role of neurotransmitters Explain the role of acetylcholinesterase

The Basic Idea Synapses are gaps between neurones 20-30nm wide Information is sent between neurones by chemical transmission Neurotransmitters pass across the synaptic cleft A new action potential will be triggered in the post-synaptic neurone

Incoming Action Potential Neurotransmitter New action Potential The basic process (GCSE level) New action Potential

Give students 2 minutes to add as many labels as they can

Postsynaptic Neurone Presynaptic Neurone Synaptic Cleft Synaptic Knob Smooth Endoplasmic Reticulum Incoming Action Potential Calcium ion channel Mitochondrion Synaptic Knob Membrane of postsynaptic neurone Synaptic vesicle containing neurotransmitter Synaptic Cleft Sodium ion channels Postsynaptic Neurone

Step 1 – Calcium Channels Open The incoming action potential causes depolarisation in the synaptic knob This causes calcium channels to open Calcium ions (Ca2+) flood into the synaptic knob

Incoming Action Potential Ca2+ Ca2+ Ca2+ Ca2+

Step 2 – Neurotransmitter Release The influx of calcium ions causes synaptic vesicles to fuse with the presynaptic membrane This releases neurotransmitter into the cleft

Incoming Action Potential Ca2+ Ca2+ Ca2+ Ca2+

Step 3 – Sodium Channels Neurotransmitter (acetylcholine) is released into the synaptic cleft. Acetylcholine binds to the receptor site on the sodium ion channels (on the post-synaptic membrane). Sodium ion channels open.

Ca2+ Ca2+ Ca2+ Ca2+ Neurotransmitter (acetylcholine) is released into the synaptic cleft. Acetlycholine binds to the receptor site on the sodium ion channels.

Sodium Channels The sodium channels on the postsynaptic membrane are normally closed. When the neurotransmitter binds there is a conformational change opening the channel. This allows sodium ions to flood in and causes depolarisation. Na+ Neurotransmitter binds and opens the channel.

Depolarised Empty synaptic vesicles Sodium ions diffuse into the postsynaptic neurone Depolarised

Step 3 – Sodium Channels Neurotransmitter (acetylcholine) is released into the synaptic cleft. Acetylcholine binds to the receptor site on the sodium ion channels (on the post-synaptic membrane). Sodium ion channels open. Sodium ions diffuse in (down steep concentration gradient). Postsynaptic neurone depolarises.

Step 4 – New Action Potential Depolarisation inside the postsynaptic neurone must be above a threshold value. If the threshold is reached, a new action potential is sent along the axon of the post-synaptic neurone.

Incoming Action Potential Neurotransmitter New action Potential

Questions When do the calcium channels open and close? Why are the calcium ions important? What is the name of the neurotransmitter? Explain how the neurotransmitter causes a new action potential to be generated.

The rest of the process Step 1 Calcium channels open Step 2 Neurotransmitter release Step 3 Sodium Channels Step 4 New action potential Step 5 Acetylcholinesterase Step 6 Remaking acetylcholine

Step 5 Acetylcholinesterase A hydrolytic enzyme Breaks up acetylcholine (the neurotransmitter) into acetyl (ethanoic acid) and choline.

Acetylcholinesterase Acetylcholinesterase is an enzyme that hydrolyses acetylcholine in to ‘acetyl’ (ethanoic acid) and choline. Sodium ion channels close. The products diffuse back across the cleft into the presynaptic neurone. This allows the neurotransmitter to be recycled.

Depolarised Acetylcholine binds and opens Sodium channels Acetylcholinesterase breaks up acetylcholine. Sodium channels close

Why break down acetylcholine? If the neurotransmitter is not broken down this could allow it to continuously generate new action potentials. Breaking down acetylcholine prevents this.

Questions Name the hydrolytic enzyme and the products of the reaction. Why must the neurotransmitter be broken down? What happens to the remnants of the neurotransmitter?

Step 6 Remaking Acetylcholine ATP released by mitochondria is used to recombine acetyl (ethanoic acid) and choline thus recycling the acetylcholine. This is stored in synaptic vesicles for future use. More acetylcholine can be made at the SER. Sodium ion channels close in the absence of acetylcholine at their receptor sites. The synapse is now ready to be used again.

The Whole Process

Incoming Action Potential Ca2+ Ca2+ Ca2+ Ca2+ Steps 1 + 2

Step 3

Step 4 + 5

Function of Synapses Synapses allow a single impulse along one neurone to be transmitted to a number of different neurones at a synapse.  A single stimulus can create multiple simultaneous responses. A number of different impulses can combine at a synapse. This allows multiple stimuli from different receptors to interact to produce a single response.

Features of Synapses Unidirectionality Summation Inhibition

Question If a neurone is stimulated in the middle of its axon, an action potential will pass both ways along to its synapses at each end of the neurone. However, the action potential will only pass across the synapse at one end. Explain why.

Unidirectionality The ‘message’ can only be sent from the presynaptic neurone to the postsynaptic neurone. This is due to the positioning of neurotransmitter vesicles and sodium channels.

Incoming Action Potential Neurotransmitter New action Potential The basic process (GCSE level) New action Potential

Summation Low frequency action potentials often release insufficient numbers of neurotransmitter moleules to exceed the threshold in the postsynaptic neurone. Summation allows action potentials to be generated. Due to a build up of neurotransmitter in the synapse.

Spatial Summation A number of different presynaptic neurones share the same synaptic cleft. Together they can release enough neurotransmitter to generate an action potential. Multiple neurones.

Below the threshold

Spatial Summation Threshold reached; action potential can be sent.

Temporal Summation A single presynaptic neurone releases neurotransmitter many times over a short period. If the total quantity of neurotransmitter exceeds the threshold value an action potential is sent. 1 neurone.

Temporal Summation Low frequency action potentials

Temporal Summation High frequency action potentials

Questions What is summation? What is the main difference between temporal summation and spatial summation? Explain how temporal summation allows the postsynaptic membrane to reach the threshold value. Suggest an advantage of responding to high-level stimuli but not low-level ones.

Inhibition There are chloride ion channels on the postsynaptic membrane If these are made to open chloride ions (Cl-) flood into the postsynaptic neurone This hyperpolarises the neurone. This make it harder to achieve an action potential.

Neurotransmitter that opens calcium channels Chloride ion (Cl-)channel on the postsynaptic membrane

Chloride ions diffuse into the postsynaptic neurone Hyperpolarised

Summation & Inhibition Inhibitory and excitatory neurones will work antagonistically at the same synapse. Summation will occur. Form neural circuits.

Neural Circuits EPSP – excitatory post-synaptic potential – generated when impulses arrive from both neurones simultaneously.  

Neural Circuits IPSP – inhibitory post-synaptic potential – where one of the neurones is inhibitory, it can prevent the threshold value being reached.  

Neurotransmitters There are dozens of different neurotransmitters (NT) in the neurons of the body. NTs can be either excitatory or inhibitory Each neurone generally synthesizes and releases a single type of neurotransmitter. The major neurotransmitters are indicated on the next slide. There are more types of neurotransmitter than just acetylcholine...

Drugs Interfere with Neurotransmission Drugs can affect synapses at a variety of sites and in a variety of ways. Look at the structure of the synapse and sequence of events across a synapse. In what ways might drugs affect synaptic transmission?

Drugs interfere with neurotransmission 1. Increasing number of impulses 2. Release NT from vesicles with or without impulses 3. Block reuptake or block receptors 4. Produce more or less NT 5. Prevent vesicles from releasing NT 6. Block ion channels

Drugs (of many) which affect Neurotransmission LSD Cocaine Marijuana Nicotine Questions on this topic usually involve interpreting data you are given.

EXAMPLE Substances from which dopamine is synthesised. Dopamine is a neurotransmitter involved in parts of the brain that control muscle action. In Parkinson’s disease, the neurones producing dopamine degenerate, leading to muscle spasms that make delicate movements difficult. What sorts of drugs would be useful in the treatment of patients with this disorder? Substances from which dopamine is synthesised. An agonist that mimics the effects of dopamine.  

Exam Questions 1a 1. (a) (i) A Three marks for three of: Negatively charged proteins / large anions inside axon; Membrane more permeable to potassium ions than to sodium ions; Potassium ions diffuse* out faster than sodium ions diffuse in; Sodium / potassium pump; Sodium ions pumped* out faster than potassium ions pumped in / 3 for 2; [3 max] * mechanism is necessary for mark

Exam Questions 1b B Sodium ion gates open / membrane more permeable to sodium ions / sodium ions rush in; [1] (ii) Two marks for two of: Membrane impermeable to sodium ions / sodium ion channels closed; Sodium ions cannot enter axon; Membrane becomes more negative than resting potential; [2 max] (b) (i) Two marks for two of: Unique shape of receptor protein / binding site; reject ‘active site’ Due to (tertiary) structure of protein molecule; Concept of complementary shape / ref. to neurotransmitter ‘fitting’; [2 max] (ii) Cause vesicles to move to presynaptic membrane / fuse with membrane; [1]

Exam Questions 1c (c) (i) Two marks for two of: Impulses / action potentials from neurones A and B together /spatial summation; Cause sufficient depolarisation / open sufficient sodium ion channels; For threshold to be reached; [2 max] (ii) Two marks for two of: Impulses from A and B independent / no summation; Threshold not reached; Insufficient sodium ion channels opened; [2 max] (iii) Inhibitory; Reduces membrane potential / makes more negative (allow hyperpolarisation) /cancels effect of action potential from A; [2 max]

Exam Questions 2a 2. (a) Initially membrane impermeable to Na+; Sodium channels open; allowing Na+ into axon; reverses potential difference across membrane/ charge on either side/depolarised; membrane becomes more permeable to K+ ions/K+ leave the axon; [max. 4]

Exam Questions 2b (i) All action potentials are the same size; threshold value for action potential to occur [2] (ii) frequency of action potentials [1] several (sub-threshold) impulses add to produce an action potential [1]