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StellwagenLecture 7
Synaptic transmission I
- Electrical synapses, pre-synaptic release, calcium dependence, quantal release, vesicle fusion
Neurons (and glia) exist in a network. Around The contacts between neurons that they moderate and
influence how the neurons work as well. Participation of glia as 3rd membrane of synaptic contact.
There’s 2 basic types of synapses, electrical
contact called gap junctions. Then chemical
synapse where we spend most time on
- An electrical synapse:
o Contact between pre synaptic cell
and post synaptic cell. So info goes
from pre to post
o Primary component is the gap
junction
o Gap junction connects presynaptic
element to post synaptic element
o Is just a pore opening that exists
between the pre and post synaptic cells
o So direct flow is possible. You can just get component from one cell to flow into the
other cell
▪ Considering flow of ions flowing through the channels
o Individual gap junctions called Connexons. Produced by both the presynaptic and post
synaptic cell.
▪ From one connexon binds to the other one tightly
o Embedded within the plasma membrane and draw the two plasma membrane tight in
opposition to each other so the pore can open directly through the connexon
▪ No transit in the extracellular space. Just interior to interior
- Transmembrane proteins have 4 transmembrane domains that allows them to create enough of
a pore opening.
- You need 6 connexons in a rowzette to create a pore
o Rarely a single protein can make the entire element
o Largely alpha helical. They combine together to combine together to create pore
opening in the middle. About 1.4nm
o Pores are not large, but large enough that a number of things can come through.
o In EM picture, you can see 2 cells, close in opposition to each other and the dark
material. Along in the membrane which the two membranes are adhere and close to
each other
▪ In EM, dark and fuzzy indicates lots of protein content.
- Connexons are not selective. It’s about charge flowing throw
- Small signaling molecules will also be able to go through
, - Not like voltage gated channel. Chronically opened
- If its stressed, might uncouple from neighbouring cells.
There is a small extracellular space where the connexons are but there isn’t much flowing through to
outside. Just some extracellular space with no communication of transiting of material.
Live staining of gap junctions
- Side view of connexon. Red is older protein and green is
newer protein
- If you actually rotate and look at it flat down from the
connexon at the entire gap junction, it actually encompasses
quite a large surface area
- Quite a lot of contact between the 2 cells meaning there’s a
lot of pores between the two cells
- Can get a significant amount of current that can flow through
- A lot of connection between the two cells
Gap junctions can pass current, as well as small signaling molecules, such as cAMP and ATP. Gap
junctions coordinate local activity in both neurons and glia.
Gap junctions coordinate local activity in both neurons and glia
- Especially astrocytes as they’re heavily jap junction to each other
- Gap junctions usually stick within type. Meaning neuron to neuron or glia to glia
Neurons particularly in adult animals, the ones that are heavily jap junction together are the ones that
need to have very tightly coordinated activity.
- For example, the ones regulating the heartbeat. You want all those neurons to fire at once and
you want the spread of activation from one cell to the rest to be very quick
- What can happen if you depolarize one cell is that you’ll get a spread of current to the
neighbouring cell. Because you’re going through the pore, it will act somewhat as a resistor, it
will allow the current to flow but it also spreads out the current a little more. You don’t
depolarize quite as much and it spreads more out in time.
o Filtering properties of passing through the gap junction.
▪ Smaller depolarization but time lag and last for longer pierod of time
- Very good because even though it’s a smaller depolarization, it will still likely cause an action
potential so the two neurons should spike together with very little jitter between the spiking
- If you record, most of the time one cell spikes, the other cell spikes too
o Occasionally you get spikes that are out of sync with each other
- Useful property to get coordinated output of a circuit
Passage of molecules between gap-functioned cells
- Also molecules that pass through, can use fluorescent dyes to these gap junctions
- Find 2 cells with gap junction and stick pipettes and get into interior of neuron.
- If you put dye in one of cells, spread through connection into neighbouring cell
- It will spread to all gap junction cells in the region.
, o For example, in the retina many cells are jap junction together. And you can go into a
particular type of retina ganglia cell and watch it spread to similar types of retina
ganglion cells in the immediate area.
▪ In the retina, the retina ganglia cells only gap junction with similar types, they
don’t gap junction with other types.
▪ It’s a way to coordinate the activity of similar type of cell in the circuit
▪ Not sharing activity with other types around.
Neuron action potential firing is imprecise business. One cell won’t trigger an action potential all the
time. It’s just that most of the time it’ll happen. Gap junctions are bidirectional. Current can flow both
ways.
- Although bidirectional flow, the flow might be better from one cell to the other based on
position of the action potential and etc.
Gap-junctions can link cells during development like postnatal development.
- Gap junctions are much more common in early development and become less common in adult
except in some circuits
- In early development, you can see a lot of gap junctions and very few known as chemical
synapse
o Cells may initially gap junction together, allows them to grow their axons and contact
neighbouring cells. They will know they’re in contact. A way to define synaptic partners
for later in development.
▪ Especially useful when cells are being generated
- Sisters cells migrate vertically into the cortex. So vertical column are all sisters.
o Most common ones to do gap junctions to do each other. And most common ones to do
chemical syntactical contacts with each other later in development.
- Gap junctions don’t have a set pre or post synapse they can flow both ways but in chemical
synapses, it’s very defined.
- Most gap junctions are not at the ends of axons. No long axon that propagates down and ends
in a gap junction to neighbouring cell. Usually a cell body cell body contact or dendrite and
dendrite contact
o Not an axon related contact
▪ As axon grows, then it forms pre and post synaptic chemical synapse
▪ And gap junction gets lost
Gap junctions can link cells during development. If they’re close to each other you can see connectivity
in cell in similar area of the cortex. If you depolarize one cell you can see current flowing into the other
cell.
- Sometimes some cells aren’t connected looking at a SCPN or CPN neuron. Each types of neurons
are usually connected with themselves; you don’t see a lot of different neurons connecting to
each other.
- Only cells very close to each other will be paired together, more distant ones are never gap
junction to each other.
o This is all early development
, Gap junction review
- Gap junctions are direct connections between cells
- Gap junctions are composed on connexons which in turn are comprised of connexins protein
units
o 6 connexins make a connexon
- Gap junctions pass current and small signaling molecules
- Prevalent during early development and coordinate activity of network of cells (both glial and
neuronal)
o Astrocytes all gap junction together and persist into adult hood because glia don’t make
chemical synapses with each other.
Cajal was looking at mature neuro systems 99% of contacts are chemical synapses with each other as
chemical synapses go in unidirectional and gap junctions go bidirectional.
Chemical synapses:
- Instead of direct electrical connections, most synapses convert the chemical signal (action
potential into a chemical signal (neurotransmitter) which is re-converted back into an electrical
signal in the post synaptic cell.
o Electrical signal is converted to chemical signal called neurotransmitter which then is
passed to the neighbouring cell and the neighbouring cell reconverts it back to a
electrical signal
- Axons commit chemical synapses. Gap junctions are faster but chemical signals are a lot more
powerful
o Can transmit variety of signals you can modulate how well signal passes through one cell
to the next by synaptic plasticity.
- Can generate signal vary in size so you can generate a signal as large as the post synaptic cell
had.
o In the gap junction, any signal going through the gap is losing signal. Depolarization of
neighbouring cell is always smaller.
- Chemical synapses are regenerative they can recreate the signal and make a signal much
stronger than the input signal.
Overview of synaptic transmission
- Release of neurotransmitter to space between the cell (Synaptic cleft) quite narrow, membrane
held tightly bound with each other with protein material across the cell holding membrane
together.
o A space of extracellular space where neurotransmitter gets released and signals to
receptors in post receptor cells.
How is the signal released:
1.) Transmitter is synthesized and then stored in vesicles
2.) An action potential invades the presynaptic terminal
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