Explore Cellular Neurophysiology at UCL with a focus on the Synapse. Unravel the intricacies of synaptic transmission, neurotransmitters, postsynaptic and presynaptic mechanisms, and the dynamic modulations shaping neural communication. Please note that these materials are intended for personal use...
Presynaptic Mechanism
Presynaptic Mechanism
Events leading to synaptic transmission
o Action potential invades synaptic terminal
o Ca2+ channels open
o Vesicles fuse with presynaptic membrane
o Neurotransmitter diffuses across synaptic cleft and binds receptors
o Neurotransmitter is eliminated from synapse
Brief history of theories of neuronal communication
Purkinje neuron
o First identified cell in the nervous system
o Structure
Large corpuscles
Layer of granules
Nerve fibres
Reticular vs neurone doctrine
o Cell theory
Biology was unified by the idea that all animals and plants were
composed of cells
o Reticular theory
Nervous system was a large, interconnected network comprised of the fused cytoplasm of
neurons
o Neurone doctrine
Application of the cell theory to the nervous system – neurons were separate entities
Soup vs spark
o Spark – initially thought that all transmission in neurons was electrical
o Soup – supported theory of chemical transmission
o Is synaptic transmission mediated chemically or by direct electrical transfer of charge
o Evidence for chemical transmission at the neuromuscular junction was widely accepted by
neuropharmacologists
o Some of the physiologists thought that certain aspects were too fast to be mediated chemically
Discovery of synaptic transmission
o Cajal’s golgi staining methods suggested the presence of contacts between cells used for
communication
Chemical vs electrical transmission
o
Electrical transmission
Voltage attenuated by resistor between two neurons
Gap junction
Lower resistance – attenuates voltage less than electrical transmission
Chemical transmission
,Presynaptic Mechanism
Transmission occurs by release of transmitter binding to specialised receptors in
postsynaptic membrane
Causes voltage change
Why chemical?
o Gap junctions
Same sign (usually)
If neuron is depolarised subsequent neuron is depolarised
Reciprocal (usually)
As resistance does not distinguish direction
Fast
Allows 2nd messengers to diffuse from one cell to another
Time course determined by time course of events of excitation or inhibition in presynaptic
cell
o Chemical synapse
Same sign or inverted
Excitatory or inhibitory postsynaptic receptor
Unidirectional
Due to presynaptic transmitter release and postsynaptic binding
Fast or slow
Depends on kinetics of postsynaptic receptor
Same signal can be decoded differently by different targets (different receptors)
Repertoire of interactions allow complex information processing
Evidence for chemical synapse
o Langley
Curare blocked transmission in ciliary ganglion
Chemical agent blocked transmission
o Eliot
Extract from adrenal glands mimicked the action of sympathetic nerves
o Loewi
Vagusstoff (vagus stuff) liberated from one heart slowed the next one – later identified as
ACh
o Dale and Feldberg
ACh was released at the neuromuscular junction and sympathetic ganglion
o Eccles
Last proponent of electrical transmission converted to chemical synapses
o Robertson
Electron microscope first used to image ultrastucture of the synapse
Model synapses
o Frog neuromuscular junction
Huge synapse with lots of vesicles released from presynaptic neuron
Lots of invagination on postsynaptic membrane
o Squid giant synapse
o Calyx of Held
Role of Ca2+ in synaptic transmission
Extracellular Ca2+ is required for synaptic transmission
,Presynaptic Mechanism
o
Calcium favours binding of vesicle to postsynaptic membrane
Magnesium inhibits synaptic transmission
Sr and Ba will partially support synaptic transmission – but release is asynchronous
Squid giant synapse
o
A
Presynaptic terminal depolarised by injection of depolarising voltage step
Inward current followed by outward current
Block Na+ and Ca2+ channels
Small inward current – mediated by Ca 2+ channels
Relationship between presynaptic calcium current and transmitter release in the squid
o
Record presynaptic and postsynaptic cell
At increasing depolarising steps – after blocking Na and K channels = only see Ca
current
As Ca current increases – causes release of transmitter = postsynaptic response
More presynaptic cell is depolarised more Ca current bigger postsynaptic
response until depolarise too much – as Ca channel inactivates = no more of
initial response
, Presynaptic Mechanism
Relationship between external calcium and transmitter release in the squid
o
Plot size of Ca current against postsynaptic response
Increase Ca current by increasing extracellular Ca followed by increase in size of
postsynaptic current
o Slope of Ca current is smaller than slope of postsynaptic response – suggests
co-operativity of Ca binding for transmitter release
If 1 Ca binds favours further binding of Ca channels
Molecular Machinery Underlying Vesicle Release
Vesicle hypothesis of transmitter release
o Vesicle docked to presynaptic membrane releases neurotransmitters into synaptic cleft
Neurotransmitter release mechanisms
o
Docking
Vesicle first binds to presynaptic membrane
Primed
Vesicle ready to release
Fusion
Once Ca enters vesicle fuses with membrane releases transmitter
Endocytosis
Vesicle is reabsorbed in membrane re-filed with neurotransmitter
Key proteins of the exocytic machinery
o SNARE proteins – soluble NSF attachment protein receptors
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