15-11-21 - Synapse 1 Flashcards
Learning outcomes
- Describe the main features of neuronal cells, their secretory function and the role of action potentials in movement of signals along neuronal cell processes
- Recall the structural features of chemical synapses, including those in the pre and post synaptic cells
- Recall how synaptic vesicle docking, fusion and exocytosis proceeds and how it can be triggered by an action potential
- Recall how vesicles are charged with neurotransmitter and the role of membrane recycling in the neuron
- Describe and distinguish mechanisms of postsynaptic receptors referred to as ionotropic and metabotropic receptors
How does where signals land on neurons affect the output of the neuron?
- Signals that land directly on the cell body of the neuron have a stronger influence on the output of the cell, as oppose to signals that land on the far end of a dendrite
- Very strong stimulation is required at the periphery to match the signal output from the same stimulation at the centre
What is the definition of a synapse?
What type of synapses are the majority?
Where are synapses primarily found?
What do chemical synapses transmit?
What do synapses act as?
How can synaptic activity be modulated (controlled)?
- A synapse is junction between 2 cells where electrical changes in one cell (pre-synaptic cell) cause a signal to be passed to another cell (post-synaptic cell), usually via a chemical neurotransmitter
- The majority of synapses are chemical synapses, but some are electrical
- Synapses primarily occur between neurones, but are also found at neuro-muscular junctions (NMJ)
- Chemical synapses transmit neuronal action potentials in one direction between cells
- Synapses act as rectifier - they prevent action potentials moving back up the axon by converting the electrical potential to chemical neurotransmitters
- Synaptic activity is modulated through neuromodulation
- The excitability of pre and postsynaptic cells is affected through the modulation of endogenous systems (receptor density, neurotransmitter production, and re-uptake ability)
What does the axon terminal form?
What is the synaptic cleft?
How large is the synaptic gap?
What do vesicles in the pre-synaptic cell contain?
How are processes in the synapses powered?
Identify these structures in the synapse
- The axon terminal (nerve terminal) swells to form a structure called a synaptic bouton
- The synaptic cleft is the gap between the pre-synaptic cell and the post-synaptic cell
- The synaptic gap is approximately 20nm (x10^-9) in size
- Vesicles in the pre-synaptic cell contain neuro-transmitters
- There are mitochondria present in the synapses which provide most of the energy required for processes within the synapses
What word describes the release of neurotransmitters?
How does number of vesicles released relate to signal?
What is the value for resting membrane potential in neurons?
What is it a combination of?
- The release of neurotransmitters is quantal (in full units of 1 vesicle, never half)
- The more vesicles released from the pre-synaptic membrane, the stronger the signal in the post-synaptic membrane
- The resting membrane potential in neurons is around -65mV
- It is a combination of electrochemical gradients and the activity of the Na+/K+ ATPase
What are the 3 categories of synaptic activity?
What are the 2 types of chemical neurotransmitters?
• 3 categories of synaptic activity:
1) Presynaptic activity
2) Postsynaptic activity
3) Neurotransmitter inactivation – to avoid accumulation of neurotransmitters and continual stimulation, neurotransmitters must be inactivated
• 2 types of chemical neurotransmitters:
1) Small-molecule transmitters
2) Peptide transmitters
Describe the 5 steps of small molecule neurotransmitters being used.
Why can’t small-molecule neurotransmitters be the only neurotransmitters used?
1) Proteins are produced on the RER, and packaged in the Golgi apparatus in the cell body to produce enzymes
2) These enzymes are slowly transported down the axon
3) These enzymes reach the synapses in the axon terminal and synthesise and package small molecule neurotransmitters into vesicles
4) These vesicles can then exocytose with the pre-synaptic membrane to release these small molecule neurotransmitters
5) After binding to postsynaptic receptors, these small molecule neurotransmitters can then be enzymatically altered into an inactive form, where they can then be reabsorbed into the synaptic bouton (axon/nerve terminal), repackaged and used again
• The process of small-molecule neurotransmitters moving from the cell body to the synaptic boutons is slow, so if we relied on this process, there would be a limited number of neurotransmitters available for use in the synaptic bouton
Describe the 6 steps of peptide neurotransmitters being used.
Why are peptide neurotransmitters not as common as small molecule neurotransmitters?
1) Proteins are produced on the RER, and packaged in the Golgi apparatus in the cell body to produce vesicles containing enzymes and pre-peptide precursors
2) These enzymes move quickly through the axon via microtubule tracks
3) When these vesicles reach the synapse in the axon terminal, the enzymes within the vesicle modify the pre-peptide precursors into peptide neurotransmitters
4) These vesicles can then exocytose with the pre-synaptic membrane to release these peptide neurotransmitters
5) After binding to postsynaptic receptors, active peptide neurotransmitters are degraded by enzymes that exist in the synaptic cleft and diffuse away
6) Glial cells can then take up these degraded neurotransmitters and reprocess them to ensure they can be used again
• The process of producing and using peptide neurotransmitters is ‘expensive’ in terms of resources, meaning they are not as common as small molecule neurotransmitters
What must also happen to vesicles in the synapse?
Why is this?
What enzyme was used to demonstrate this?
What are the 4 steps in this experiment?
- Vesicles in the synapse must also be reabsorbed back into the synaptic bouton and recycled
- If the vesicles fuse without being reabsorbed and recycled, this will result in a much larger membrane than before
- An enzyme called HRP can be used to demonstrate this
1) The axon terminal is stimulated by HRP
2) This results in receptors in coated pits binding with HRP and endocytosing into the cell to form vesicles. Any extracellular HRP is washed away
3) The HRP is then delivered to an endosome within the synaptic bouton
4) Synaptic vesicles containing HRP are then produced
Describe the 6 steps of vesicle docking and fusion at the presynaptic membrane
1) The v-snare proteins on the vesicle complexes recognise the t-snare proteins on the presynaptic membrane
2) The v-snare and t-snare proteins form a complex which folds in order to bring the vesicle closer to the membrane
3) Th vesicle docks on the presynaptic membrane, but exocytosis is block by the protein complexin
4) An action potential triggers an influx of calcium into the synaptic bouton from a calcium channel
5) Calcium induces synaptotagmin to displace complexin, which allows fusion between the vesicle and presynaptic membrane to occur – this neurotransmitter release takes place 0.2ms after calcium entry
6) Exocytosis then occurs
What is embedded within the postsynaptic membrane?
What are the 2 different types?
• Embedded within the postsynaptic membrane are membrane spanning proteins called receptors
• There are two types of receptors:
1) G protein coupled receptor group (metabotropic receptors)
2) Ligand gated ion channel group (ionotropic receptors
How do ionotropic receptors (ligand gated ion channels) open?
What can this channel be specific to?
What 2 things stops other ions/molecules moving through?
What does movement of charged molecules across the postsynaptic membrane cause?
What are the 2 results of this?
- In ionotropic receptors, when a ligand binds to its binding site, it induces a conformational shape change in the receptor, such that a pore from the inside to the outside of the cell is formed
- This pore/channel can be specific to 2 or 3 ions
- The pore itself has charges across it which will only allow specific ions through
- The size of the pore may also limit the movement of larger molecules through the cell membrane
- Movement of charged molecules across the postsynaptic membrane will change the charge separation across the postsynaptic membrane (membrane potential)
• This will result in:
1) An excitory charge (depolarisation)
2) An inhibitory charge (hyperpolarisation)
What are G proteins not directly linked to?
Describe the 7 steps that allow G-protein linked (metabotropic) receptors) to open/close ion channels in the postsynaptic membrane
• G proteins are not directly linked to receptors or ion channels
1) A neurotransmitter binds to a receptor in the postsynaptic membrane, which causes a conformational shape change in the receptor, allowing the G protein complex to bind to the intracellular component of the receptor
2) This binding alters a sub lobe of the G protein complex, which allows the complex to release GDP and bind GTP, making it charged with energy
3) In his state, part of the G-protein complex splits off and interacts with an enzyme bound enzyme, which activates with enzyme to produce messenger molecules from precursors floating in the cytosol
4) These messenger molecules interact with the intracellular portion of anion channel, opening it
5) When the GTP is used up, a phosphate is released from the part of the G-protein complex, reverting it to its inactive form. It stops binding to the membrane bound enzyme, which stops the production of messenger molecules.
6) In the G-proteins GDP state, the conformation of the G-protein piece reverts so that it can rebind to its original part
7) The neurotransmitter releases from the receptor, and the receptor conformation reverts to normal, so the G-protein complex can no longer bind to it. The process is back to the beginning
What are postsynaptic potentials (PSPs) caused by?
How are excitory postsynaptic potentials (EPSPs) formed?
How can a threshold potential be generated from a EPSPs?
How does decay time of EPSPs compare with that of action potentials?
How are inhibitory postsynaptic potentials (IPSPs) generated?
How is amplitude of EPSPs and IPSPs altered with distance and time?
- Postsynaptic potentials (PSPs) are caused by the passage of ions through ion channels, which have been opened following receptor/neurotransmitter reactions
- EPSPs are caused by a net flow of positive (e.g Na+) ions into the cell, which depolarises the membrane and brings the membrane potential closer to the threshold potential
- Single EPSPs rarely generate an action potential
- Often times, multiple EPSPs are needed to add up to the threshold potential to generate an action potential (this is known as summation)
- ESPS are much slower to decay than action potentials
- IPSPs are caused by a net flow of negative ions (e.g Cl-) into the cell, which hyperpolarises the membrane and brings the membrane potential further from the threshold potential
- The amplitude of EPSPs and IPSPs decreases with distance from the synapse and time
What do single EPSPs rarely generate?
How does refractory period between ESPS and action potentials differ?
What is spatial summation?
What does this result in?
What is temporal summation? What does this result in?
- Single EPSPs rarely generate an action potential
- Unlike action potentials, EPSPs don’t have a refractory period
- Spatial summation is when signals from multiple axons of other neurons synapse on the same dendrite of a neuron, which results in multiple EPSPs being generated in the postsynaptic membrane
- This results in the summation (addition) of all the EPSPs together, which triggers a larger depolarisation that is closer to/may reach the threshold potential required to generate an action potential
- Temporal summation is when 1 axon sends along multiple signals close together that result in multiple EPSPs being generated in the postsynaptic membrane
- Since EPSPs are slow to decay, the cell will still be in a state of depolarisation when more signals arrive, which results in the membrane potential being able to get closer to threshold potential to generate an action potential
How do EPSPs and IPSPs together affect the generation of an action potential?
