Lecture 5 - Synaptic transmission I - general features Flashcards
Excitability of neurons conferred by
expression of channels that allow depolarisation when activated
If local potentials reach threshold for voltage-gated Na+ channels…
an action potential is initiated
‘Presynaptic cell’ is postsynaptic to its
Afferent inputs
Presynaptic and postsynaptic are relative to the synapses you are looking at in the moment
Almost every neuron you come across will have some synapses coming in and some synapses coming out therefore every single neuron itself is both presynaptic and postsynaptic
Electrical synapse
Gap junctions are essentially pores formed between the membranes of cells, they are specialised proteins in the membrane that make pores, one set of proteins in the presynaptic cell and one set of proteins in the post synaptic cell that join up to form a pore and this is not open all the time and it only opens in response to a change in the membrane voltage
Opens when the presynaptic cell becomes depolarised by becoming electrically excited which causes a conformational change in the proteins which opens the pore in the middle and allows the flow of ions which means that the depolarisation can be passed on to the post synaptic cell
Closed most of the time
Communication is very fast
Ions flow from cell to cell
The way we modify things here compared to chemical synapses is by adding more or less gap junctions which takes time since you have to synthesise more proteins in order to form these pores in the electrical synapse
Can be opened by voltage, pH, Ca2+ and receptors
Electrical synapse is also called
a gap junction
Chemical synapse
Slower as it is a more complicated process
Relies upon chemicals crossing the gap
Complex series of events
Neurotransmitter packaged in vesicles
Synapse strength can be modified (perhaps by modifying the phosphorylation level of proteins that are involved in that transmission)
Classical transmission (small molecule neurotransmitters diffuse across the synaptic cleft and bind to postsynaptic receptors), gaseous transmission (gaseous transmitters diffs out of the cell of origin and directly into other cell) and neuropeptide transmission (peptides diffuse in extracellular space and bind to synaptic and extra synaptic G protein-complex receptors)
The ionic conduction causes a change in membrane potential and that
neurotransmitter release etc. takes longer than direct conduction of ions through gap junctions
Neurotransmistter exocytosis - Classical-full diffusion
Vesicles fully fuse with the membrane and essentially flatten out and become part of the membrane and everything inside the vesicle gets spilled out into the extracellular space which in this instance would be into the synaptic cleft
Neurotransmitter exocytosis - Kiss and run- partial diffusion
The vesicle does not fully fuse to the membrane surface, instead partially fuses and forms a hole but does not flatten out to become part of the membrane - it essentially stays as a vesicle and just sticks to the sides of the membrane.
It is more difficult for the contents to get out therefore this type pf fusion may deliver less neurotransmitter into the synaptic cleft than full fusion particularly if its peptide
Clathrin
The little proteins called Clathrin mark the membrane as special and helps machinery inside the cell to essentially fold that back into a vesicle shape and it gets taken back up into the presynaptic terminal and filled with more neurotransmitter and goes into the reserve pool and it will later be back in the readily releasable pool which is right near the surface of the icon terminal and release the contents etc
Sequence of events during classical chemical neurotransmission
Action potential propagates down the axon to the presynaptic terminal (do not say synapse here as the synapse is the presynaptic terminal AND the postsynaptic membrane
Presynaptic terminal is depolarised and voltage-gated Ca2+ channels open (and you get a calcium influx)
Ca2+ ions trigger vesicle fusion with the presynaptic membrane (the fusion may be full exocytosis or partial exocytosis)
Neurotransmitter is released into the synaptic cleft - vesicle is recycled, “kiss and run” - usually happens within one second
Neurotransmitter diffuses with the synaptic cleft
Neurotransmitter binds to its specific receptors on the postsynaptic membrane
(A) Na+ channels open - local postsynaptic cell depolarisation - the excitatory post synaptic potential (EPSP) (switches the next cell off rather than turning it on) OR (B) K+ or Cl- channels open - local postsynaptic cell hyper polarisation - the inhibitory post synaptic potential (IPSP)
Neurotransmitter degraded or taken up (by glia or presynaptic terminal) (when into presynaptic terminal it will be recycled and repackaged for rerelease)
Recycling and refilling of the vesicles - Clathrin mediated in ~20 seconds
Synaptic integration define
Synaptic integration is the term used to describe how neurons ‘add up’ these inputs before the generation of a nerve impulse, or action potential
May be as many as 50,000 synapses on a single neuron
Integration of those signals from those synapses takes place within the neuron
Temporal summation
Summation between EPSPs from the same input that occur close enough together in time
Same synapse
Spatial summation
summation between events that occur close enough together in space from different inputs - still requires them to be close in time
Two different synapses in two different places at the same time/very close in time
Passive local potentials =
IPSP and EPSPS
IPSP
Inhibitory postsynaptic potentials (IPSP) - chemical stimulus opens potassium ion channels causing hyper polarisation as K+ moves out of the cell
Inhibitory because the membrane is going away from threshold, going more negative and when it does this there is less likelihood that an action potential being delivered
EPSP
Excitatory postsynaptic potentials (EPSPs) - depolarisation caused by the opening of Na+ ion channels allowing an influx of Na+ into the cell moving the cell closer to threshold to trigger an action potential
Synaptic modulation
Synaptic modulation is an observed change in the synaptic function
Synaptic modulation - facilitation within a single synapse
Lasts seconds to minutes
Increased presynaptic calcium and/or neurotransmitter availability
Summation is about what happens in the post synaptic cell but facilitation is happening in the presynaptic terminal
The presynaptic cell is firing so fast that the calcium in the presynaptic terminal can’t be removed so each time the action potential fires in the presynaptic cell there is still come calcium remaining from the previous one and this builds up and up so you get a bigger response because there is more calcium
Key thing is that it modulates the strength of that synapse and the more active a synapse is/the faster it fires, the more influence it has on a postsynaptic cell
Synaptic modulation - long term potentiation (and depression)
Lasts hours to days
Multiple post synaptic mechanisms
Insertion of more receptors that respond to the more active synapse
Shunting
on the same dendrite therefore when they fire close enough together the channels in that dendrite are open and so when the next signal comes you can’t open them any more and this is known as SHUNTING
Shunting causes …
Shunting causes sublinear summation which is where EPSPs are intiated in DIFFERENT inputs close together on the SAME dendrite
No linear summation with shunting
EPSPs and IPSPs are recorded in the
cell body
Synapses closer to the __________ will have more of an impact than synapses ________
cellbody
far away on a dendrite
Long term potentiation
strengthening of a synapse
Insertion of more receptors because the synapse is active which shows it is important because it is being used
Long term depression
weakening of a synaptic connection
Facilitation
When the presynaptic neuron is stimulated with several consecutive individual stimuli, each evokes a larger postsynaptic potential than the previous stimuli
Cause = prolonged calcium channel opening
Consequently another excitatory signal entering the neuron from another source can excite the neuron very easily
A higher concentration of calcium enables synaptic vesicles to fuse to the presynaptic membrane and release their contents (neurotransmitters) into the synaptic cleft to ultimately contact with receptors on the post synaptic membrane. The amount of neurotransmitter released is correlated with the amount of calcium influx. Therefore short term facilitation results from a build up of calcium within the presynaptic terminal when action potentials propagate close together in time
When neurons are repeatedly activated their synaptic connection may become stronger and this effect may last for milliseconds
Synapse is very active and over time there is a bigger response in the post synaptic cell through modifications in the presynaptic terminal
the axon hillock is the
site of action potential initiation, gate keeper of action potential
it must be big enough to reach threshold at the axon hillock in order for an action potential to be propagated
If the input from one synapse is further away than another
than the recording on the electrode will show the the response form the furthest away synapase is smaller (local potential decreases over time)
