Synapses Flashcards
What problems do synapses help overcome?
Transmission of an electrical signal across a high resistance membrane and intercellular gap
What is a synapse?
A specialised junction between two neurons?
What do the presynaptic and postsynaptic neurons do and what is between them?
- Presynaptic neuron: sending the information
- Postsynaptic neuron: receiving the information
- Synaptic cleft of varying length is between them for the signal to cross
What causes a postsynaptic potential?
Action potential in the presynaptic neuron
What does it mean that the direction of transmission is rectifying?
It is one way
What is another name for electrical synapses?
Gap junctions
What do electrical synapses do?
Directly transfer ions and small molecules between cells
What does it mean that the electrical synapses are bidirectional?
Current can pass in both directions
Is there a synaptic delay with electrical synapses?
No - there is fast transmission
Is there action potential: action potential transmission of the signal with electrical synapses?
No - in the postsynaptic cell you will see an attenuated signal compared to the presynaptic cell
What do gap junctions allow?
direct cytoplasmic communication between cells
What are electrical synapses made up of?
many gap junction ‘channels’/pores. Each channel is made up of two connexons and each connexon unit is made up of six connexin subunits. You can got homotopic and heterotopic connexons depending on whether all the connexin subunits are the same of not
Give a summary of electrical synapses
- They are fast
- Many be two-way (non rectifying)
- Can give one-to-one transmission but signal often attenuated
- Allow exchange of other chemicals
- Used by invertebrates, lower vertebrates and mammals
- Much less common than chemical synapses
- Used in fast pathways e.g. escape/ defence
- Used to promote synchronous activity within a network
- Electrical synapses are fast and reliable but are capable of only limited plasticity (contrasts chemical synapses)
Talk about the electrical synapse and the fly
- Electrical synapses are used for a fly to get away from a predator
- First the eyes and so optical lobes are shadowed by a predator
- The giant fibres take the signal down through the neck to the thoracic mass which is where the wings and legs are activating the jump muscle and flight muscle
- If fluorescent dye is injected into giant fibre we find that injecting one neuron stains the entire circuit of the jump and flight muscles: this proves the whole circuit is connected by gap junctions.
- Evidence: They found a mutation you can squash and the fly won’t jump – this mutation coded for a gap junction
Which type of synapses are plastic?
Chemical synapses
What is the synaptic delay in chemical synapses?
0.5-2.0 milliseconds
How did Otto Loewi prove the existence of acetylcholine?
- Experimented with frog heart neuromuscular junction
- He took out a frog heart with a vagus nerve attached, put it in a saline bath and stimulated it. He found that the heart slowed down (this was because of the Vagus nerve)
- This is because heart stimulates acetylcholine
- He had a second heart that wasn’t stimulated, and the saline fluid that surrounded the first heart was pumped into the second heart
- Found that the second heart slowed down too, clearly demonstrating there was a fluid soluble thing in the saline that slows down the heart.
What happens with vesicular release?
- Neurotransmitters are packaged into synaptic vesicles
- Action potential invades presynaptic terminal
- Calcium channels open and calcium enters terminal
- This causes vesicles to fuse and release neurotransmitter
- Neurotransmitter diffuses across synaptic cleft to postsynaptic membrane
Where is there a high concentration of mitochondria in the presynaptic terminal?
Close to where vesicles are released
What is the SNARE hypothesis?
- Number of different proteins that anchor into membrane bilayer and protrude out into the cytoplasm:
- V-SNAREs interact and bind to t-SNAREs
- About 60 different proteins
- V-SNAREs (vesicle) = synaptobrevin, synaptotagmin
- T-SNAREs (target membrane) = syntaxin, SNAP-25
- Proteins form a ‘zipper’ and pull the membranes close together
- Energy needs to be surmounted to get the vesicles to fuse together
- Synaptotagmin is a calcium sensor. As a calcium channel enters close by it will bind to synaptotagmin, this causes the complex to tighten up and forces the membrane together, causing vesicle fusion.
- The v-SNARE and t-SNARE complex is the strongest protein interaction you would know
- Calcium is the trigger for vesicular release
What may still happen in the absence of Ca2+?
Spontaneous neurotransmitter release due to spontaneous vesicle fusion. However, usually only a single vesicle will release
Why will an action potential release more transmitter in the presence of calcium?
Because all of the docked vesicles will fuse and release
What proves that you have spontaneous release in vesicles?
- Electrode was put into muscle cell which was stimulated with an action potential (and calcium) you get a large PSP
- If it was stimulated with no calcium you will still see very small PSPs
What does it mean that Neurotransmitter release is quantal?
- Each of the vesicles in the terminal have the same amount of neurotransmitter as each-other
- If you measure the frequency at which the vesicles all release spontaneously the probability is very low
- 1 quanta = amount of transmitter per vesicle – you will never get a half as not half a vesicle can be released
What does quantal content show?
The strength of a synapse and the number of quanta released for one Action potential
How do you work out quantal content?
evoked/ spontaneous
Talk about miniature postsynaptic potentials
- Occur spontaneously even in zero extracellular Ca2+
- Have amplitudes that are multiples of a quantal unit
- Are due to release of one or a few quanta (=vesicle)
- As extracellular Ca2+ is lowered, epsp amplitude decreases in a step-wide manner
Why does recycling in vesicles need to happen?
Otherwise the presynaptic membrane would expand
What happens with vesicle recycling?
- Once a vesicle is released another part of the membrane is pinched in (endocytosis) to reform a vesicle
- Key that all vesicles are the same size
- Clathrin – a protein used to build intracellular membrane-bound vesicles. Provides a structure within which the vesicle can form – vesicle breaks down after
What do Omega-conotoxin, Botulinum toxin and Alpha-bungarotoxin do?
- Omega-conotoxin – from marine coneshell. Blocks Ca channels
- Botulinum toxin – from botulinum bacteria. Blocks neurotransmitter release
- Alpha-bungarotoxin – from snake venom. Binds acetylcholine receptors.
Give features of BOTOX (Botulinum toxin)
- Produced by the bacterium Clostridium Botulinum
- Responsible for fatal cases of food posisoning
- Destroys SNARE proteins
- Blocks neuromuscular junction -> paralysis
- Botox as experimental tool
- Cosmetic: reduces wrinkles – especially in the face
How can BOTOX be used as a therapeutic drug?
- Therapeutic- to treat: Excessive sweating Muscle spasticity associated with upper motoneuron syndrome (cerebral palsy) and stroke, where muscles show loss of reciprocal inhibition Strabismus (misalignment of eyes) Chronic migraine
What is Tetanus caused by?
the anaerobic bacterium Clostridum tetani which is related to Clostridium botulinum
What does Clostridum tetani do (in Tetanus)?
It cleaves snare proteins and causes muscle spasms (unlike botulism which produces muscle weakness and flaccid paralysis)
What does the difference between the tetanus and botox disorders arise because of?
Arises because of the types of neuron which are targeted by the toxin
What is the pathology of Tetanus?
- Like botulinum toxin, tetanus toxin binds to and enters presynaptic nerve terminals in the skeletal muscle neuromuscular junction. However, it does not cleave the snare proteins in the nerve terminals. IT travels back up the motor neuron axon into the CNS
- There it is released from the dendrites of the motor neuron and is taken up by inhibitory neurons. These neurons normally release GABA or glycine.
- Once in the inhibitory neurons, tetanus toxin destroys their SNARE proteins and stops them from releasing GABA or glycine
- The normal function of these inhibitory neurons is to regulate the motor neurons that stimulate skeletal muscle contraction. When this regulation is lost, the skeletal muscle will go into uncontrollable spasms. This leads to breathing problems and has a mortality rate of around 10%
