What are the two types of synapse?
Chemical and electrical
Stages of the monosynaptic stretch reflex arc
- Sensory nerve generates AP
- Releases L-glutamate at synapse in spinal cord
- L-glutamate binds to AMPA receptors on motor neuron
- AP triggers in motor neuron
- Motor neuron releases Ach at neuromuscular junction
- Ach binds to nAchRs
How many types of neurotransmitter can a neuron release?
One
e.g. glutamatergic or GABAergic
How many synapses are there in the human CNS?
10^14
Two methods by which synapses can be viewed
Electron Microscopy
Fluorescent Immunostaining
How does fluorescent immunostaining work?
Synapsin is only present in presynaptic terminals
PSD95 protein is only present in postsynaptic terminals
Functions of the hippocampus
Learning
Memory
Spatial Navigation
4 types of neurons present in the hippocampus
CA1 pyramidal neurons
CA3 pyramidal neurons
DG pyramidal neurons
OLM interneurons
Diameter of synaptic vesicles
40nm
How are vesicles filled with neurotransmitter?
Vesicle membranes have ATPase protons pumps that pump protons into the vesicle
A proton/neurotransmitter antiporter uses the proton gradient to bring neurotransmitter in
Exchangers are specific to one type of neurotransmitter
Cycle of a vesicle
- Vesicles dock with the presynaptic membrane in the terminal bouton
- Arrival of an AP opens VOCCs
- Vesicles detect calcium, the docked vesicles fuse with the membrane and exocytose their contents
- Empty vesicles pinch back off membrane via clathrin mediated endocytosis
How many genes to vertebrates have for calcium channels?
10
Which types of calcium channels are present on terminal boutons?
N-type (CaV2.2)
P/Q type (CaV2.1)
What is the SNARE hypothesis?
Vesicles have vSNARE proteins
The presynaptic membrane has tSNARE proteins
vSNARE + tSNARE = SNARE complex
What are the proteins in the SNARE complex?
Synaptobrevin: Part of vSNARE. Is a small membrane protein
Syntaxin: Part of tSNARE. Positions vesicles at the site of calcium ion entry
SNAP25: Part of tSNARE. Dampens the calcium channel function
What is the structure of the SNARE complex?
3 Proteins
4 helix bundles
What is synaptotagmin?
A protein present in the presynaptic membrane
Modulates exocytosis
Senses formation of a calcium microdomain following VOCC activation
What 3 things does synaptotagmin do?
It has a C2B domain that facilitates vesicle docking on the membrane
It has a C2A domain that facilitates vesicle fusion
It also displaces the complexin protein in the SNARE complex to stop exocytosis
How does Botox work?
Targets protein within SNARE complex to prevent exocytosis of Ach at the neuromuscular junction
What is synaptic probability of release?
The probability that a synapses will release neurotransmitter upon arrival of an AP
The probability is stochastic (random)
Measured on a scale from 0-1
Probability not same for all synapses on one neuron
How is population mean probability of release calculated?
(Average number of synapses activated per AP)/(Total number of synapses)
What is minimal stimulation?
The electrical stimulation required to activate one synapse
How is synaptic probability of release measured?
Single cell post synaptic recording
Record using minimal stimulation
Good if you can find two neurons connected by a single synapse - otherwise you don;t know which synapse is carrying the message
What are the two ways probability of release can be altered?
- Manipulating calcium ion concentration
2. Short-term synaptic plasticity, dependent on prior synapse activity
