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Title: Neuroscience - Pre-synaptic Events - Lecture 3
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They include PowerPoint slide screens and the relevant notes underneath them, and boxes including relevant questions underneath.
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They include PowerPoint slide screens and the relevant notes underneath them, and boxes including relevant questions underneath.
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Lecture 3
Presynaptic events in neurotransmission
1-In pre synaptic nerve terminal its calcium that’s the major trigger, Voltage gated calcium
channels open when AP arrives when the membrane depolarises, calcium enters the cell
...
3/4- Diffuse across cleft- not very big, only 50nm, diameter of a synaptic vesicle
...
Interacts with receptors on post synaptic membrane
...
Can affect ion influx efflux
5/6- neurotransmitter can go back on itself, feeding back to how the synapse is working
7-leaks out synapse, impacting on other synapses
8- Signalling stops by neurotransmitter leaving in some way
9/10- takes vesicle back into pre synaptic membrane, they are limited so are taken back to
be recycled
...
Only about 1micron in
diameter for pre cant stick electrode in that! Post neuronal soma, can easily
measure
...
How was this discovered? Applied electrophysiology to synapses
...
This makes it really impossible to work on
...
They
put electrode in the synapse, record from the muscle
...
Inhibited na/k channels
...
And killer toxin TTX tetrodotoxin from puffer fish which inhibits
Na+ channels
...
Changed membrane potential, measured
calcium currents which then causes depolarisation in muscle (causing contraction)
...
There a synapse in hearing circuit- synapse of helm?
Post synaptic potential graph- could measure potential of pre
...
Evidence of ca importance
Calyx of held synapse in hearing circuit
Ca2+ is very similar to K/Na, look very similar
...
Each subunit is monomeric and there's 4 which form tetramers
which form the channel
...
Practically no ca in cytoplasm, lots coming in at once causes a big signal, causes the
vesicle exocytosis to occur
...
Remove ca, stops AP but miniEPPS don’t stop shows they are ca independent
...
From giant axon again- stimulating the axon and recording Pre cell and recording the muscle
potentials
...
B stimnulate motor axon at time 0, 2ms later get an
AP in post cell
...
These are mini end plate potentials
...
4mV
...
4
...
4mV
...
4,
without ca they don’t occur
...
Each one
corresponds to synaptic vesicles
...
Therefore amplitude would be 35x0
...
Shows synaptic vesicles at the plasma membrane, ready to be released, normally there's a
calcium signal to be released but the membranes spontaneously fusing with plasma
membrane releasing content the getting a tiny little blip
...
When Ca is taken down to 0, no ca outside the
cell
...
Jim Rothman/Tom suedoff
Needs to be a calcium receptor- protein called synaptotagmin
...
The fusion machinery does the fusion- SNARE
...
The synapse recycles the vesicles in order to
maintain stimulations for long periods of time
...
They are
packed with mitochrondria, very energy hungry from pumping all ions etc
...
Only get vesicle release, its quantal, only
get a defined amount
...
200 proteins in plasma membrane
...
Fusion- fusion machinery, many more
proteins than SNARE
...
ATPase which pumps protons into vesicle to make it
acidic
...
Some involved in docking
...
Jim Rothman there are proteins mostly on vesicle and some are mostly on the plasma
membrane
...
This pulls the
membrane together
...
Only do it if synaptotagmin and calcium are aroundphysically specific
...
They determine the excitability of most synapses
in the brain
...
They all have their own specific
receptors on the post synaptic membrane
...
Whether it fires AP
is determined by sum of all
...
In cerebellum- cells are gabaeric
...
How to regulate pre synaptic nerve terminal
...
Different
ways: calmodulin- ca binding protein can bind to loop in the channel making it bind more
easily
...
SNARE proteins can also bind to the channels so the vesicles are next to the channels o
when ca enters through the channel it’s instantly there to cause the immediate release
...
Epilepsy- get abnormal synaptic activity
in an area of the brain
...
Current drug targets SV2A
...
If you
inhibit this the synapse can cope under normal conditions, when an epileptic fit occurs cant
be endocytosed so fit cant continue
Title: Neuroscience - Pre-synaptic Events - Lecture 3
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They include PowerPoint slide screens and the relevant notes underneath them, and boxes including relevant questions underneath.
Description: My notes from my module 'Neuroscience' made in my second year at the University of York. They include PowerPoint slide screens and the relevant notes underneath them, and boxes including relevant questions underneath.