Lecture 6 - Synapses Flashcards
How many synapses are there in the human cortex?
Neurons - 20 billion
Over 1000 synapses per neuron
Total: 20 trillions I.e > 20 x 10^12
What are some synapses?
Excitatory
Increasing the response of a post-synaptic neuron
What are some examples of excitatory neurotransmitters?
Glutamate
ACH
What are some examples of inhibitory neurotransmitters?
GABA
Glycine
What determines the neurotransmitter action?
The properties of the receptors
Why did B.Katz win the Nobel prize?
Understanding quintal neurotransmission
What did B.Katz work on?
Nerve muscle junction
How are neurotransmitters released into a synapse?
Packaged vesicles called quanta
What does one quantum generate?
Miniature end plate potential
What is miniature end plate potential?
Smallest amount of stimulation that one neuron can send to another neuron
What is Quantal release a mechanism of?
Most traditional endogenous neurotransmitters are transmitted throughout the body
What 2 types of molecules does chemical neurotransmission rest on?
Chemical messengers
Chemically gated receptors
What plays an important role in giving rise to a negative membrane potential?
Electrochemical gradient for K+ ions
Why is ACH receptor not selective between sodium and potassium ions?
It has a reversal potential of 0 millivolts
Ena
Positive
Ek
Negative
NACh receptors
Ionotropic receptors
Respond to chemical stimulus and incorporate an ion channel
What is the structure of NACh receptors?
Formed from 5 subunits
Subunits have alpha helical domain
What happens in the absence of ACH?
H20 is being excluded
Alpha helices are stuck together
What holds the channels closed?
Hydrophobic interactions
Where does ACH bind?
At C loops on the alpha subunit
Outside the inter membrane domain
What helps shape the ACH binding pockets?
Gamma or delta subunit
Where was 2 sharp micro electrode inserted into muscle fibre?
One close to NMJ
The other can move at flick of switch
How is synaptic potential generated?
When you send action potential down the motor axon that is connected to muscle fibre
What happens to the micro electrode close to the NMJ?
Rapid rising of EPP
What is NMJ?
High-fidelity junction
What happens when you move the microelectrode further away?
The EPP gets smaller
Rise of EPP gets smaller
(Moving away from the source of depolarising current)
What does muscle fibre membrane have?
Capacitance
What is the source of excitation in muscle fibre?
End plate
What was NMJ initiating?
Excitation in the muscle fibre
What does a single quantum cause?
Only a slight depolarisation
What happens when the electrode is inserted into muscle fibre very close to the NMJ?
Send impulses down motor axon
Record AP
What occurs when electrode is recorded away from end plate?
No EPP is seen
Just AP
How are tiny little blips recorded?
If amplifier is increased when electrode is near NMJ
What occurs spontaneously in muscle fibre?
Tiny miniature potential
How is the release of neurotransmitters at NMJ controlled?
Electrically
What kind of recording is done in a muscle fibre?
Intracellular
What is the release of neurotransmitter from presynaptic terminal dependent upon?
Presence of Ca2+
Where must Ca2+ enter to trigger the release of neurotransmitter?
Pre-synaptic terminal
What is not random but related?
The relationship between releasing neurotransmitters and the size of EPP recorded in a muscle fibre
How is EPP generated?
Release of many N.T
What is present on the post-synaptic membrane?
Junctional folds
What is Acetylcholinesterase?
the enzyme that is responsible for breaking down ACH and terminating it’s action
What is the role of Snare proteins?
Mediate vesicle fusion
What is snare protein a primary target of?
Botulinum
Tetanus toxins
What does synaputogamin-1 induce?
Transduction the Ca2+ signal into membrane “bending”
What is present in the synaptic cleft?
Acetylcholinesterase
What can neurotransmitter breakdown be inhibited by?
Organophosphate nerve agent
e.g. sarin (nerve gas)
Insecticide
What is neurotransmitter breakdown medicinally inhibited by?
Neostigmine
Physostigmine
What are the reasons for chemical transmission at NMJ?
Presence of miniature and analysis of EPP amplitude suggest transmission is based on quantal mechanism
Functional synaptic transmission requires entry of Ca2+ into presynaptic terminal
Presynaptic terminal typically contain membrane bound vesicles
EM: exocytosis of vesicles takes place with nerve stimulation, and that neurotransmitter is released into synaptic cleft
Transmission is unidirectional
Protein complex involved in exocytosis require Ca2+ entry
Nicotine acetylcholine receptors are found expressed at postsynaptic membrane
Immunohistochemical data puds Acetylcholinesterase in post junctional gold
Blocking NT release or breakdown alters characteristic of transmission
Autoantibodies against acetylcholine receptors cause myasthenia graves
What does neurotransmitter release in CNS cause?
EPSP
IPSP
In the postsynaptic cell
EPSP
1a afferent reflex arc
Reflex that give rise to knee jerk
Hamstring contain muscle spindle
When you hit the ligament it is stretched
Give rise to AP/impulse which go up the sensory pathway
Make monosynaptic connection with a same motor neuron
Alpha motor neuron sits in the central horn of spinal cord and connects to same muscle
What is Glutamate receptor?
Excitatory synapse that give rise to depolarisation
Glutamate receptor: ionotropic
What does a central axon lead to?
Pre-synapse
What are examples of glutamate receptors?
Kinate receptors
NMDAR
AMPA
What is Dales principle?
Each synaptic connection made by a single neuron utilises the same chemical transmitter
Renshaw Inhibition
The first functional central circuit to be discovered
Inhibitory neuron: grey matter of spinal cord
Associate 2 ways:
Receive excitatory collateral from alpha neurons axon as they emerge from motor root and informed of how vigorously that neuron is firing
Renshaw cell synapses with multiple neuron
Elicit IPSP in alpha motor
1a inhibitory internueon and gamma motor neuron
What is reciprocal antagonist inhibition?
When the CNS sends a message to agonist muscle to contract, the tension in Antagonist muscle is inhibited by impulses from motor neuron and thus must simultaneously relax
Mechanism of IPSP
Glycine/GABA a receptor Ionotropic receptor Linked with an ion channel Cl- crosses the membrane Give rise to hyperpolarisation
What is Risus sardonicus?
High characteristic, abnormal sustained spasm of facial muscle that appears to produce grinning
Where is Glutamate taken up in?
Pre and post synaptic terminals and into adjacent glia
The transporter uses energy stored in the transmembrane Na* gradient to uptake glutamate
Synaptic plasticity
Long lasting potentiation
Record extracellularly in dentate gyrus
Extracellular recording is altered by tetanizing activating performant path at high frequency
Synaptic depression and potentiation are both apparent in CA1 region of hippocampus
What is LTD linked with
?
Activation of G protein coupled glutamate receptors morning
Dudek + Bear
CA1 hippocampus (pyramidal neurons)
If you use 3hg to excite an input pathway to CA1
You can depress the synapse (LtD)
If you use 10hg stimulation - no long term effect on synaptic strength
50hg briefly —> generate LTP
Long term synaptic plasticity
Memory storage
What is the molecular mechanism of sensitisation in Aplysia?
Activate 5HT receptors
Release serotonin which acts on G protein coupled receptors
Activated pka
Action on potassium channels
Increase pka = translocated into the nucleus
Gives rise to the activation of protein synthesis
When KREB1 and KREB2 are bound together in the nucleus of a sensory neuron - become inactive
