L12 - LTP Flashcards
What is the Hebbian synapse?
Coordinated activity of presynaptic terminal and a postsynaptic neuron strengthen the synaptic connections between them
How was the idea of the Hebbian synapse tested?
Tested on the hippocampus
- Evidence hippocampus is involved in memory
- Alzheimers hits the hippocampus early
Simplified hippocampal circuits
- Input –> dentate gyrus – performant
- Dentate gyrus –> CA3 – mossy fibred
- CA3 –> CA1 – Schaffer collaterals
- Output via formix and subiculum
What is the most important synapse to study for LTP and LDP?
Synapse between CA3 and CA1 neurons
How is LTP phenomenon tested?
Usually tested using CA3 to CA1 synapses
- Use two different electrodes
- Produces an EPSP
- Activated CA3 cells with high frequency stimulus - produces a long-lasting potentiation
What two characteristics does LTP show?
Input specificity
- Only synapses in input 1 affected not input 2
- Mechanism of LTP is located in synapse not cell bodies
Cooperativity
- Do not need high frequency stimulus of synapse to trigger LTP
- Can depolarise both presynaptic and postsynaptic neurons at the same time
What is associative learning?
Two pathways converging on the same target can both be strengthened if they fire together
- Use both conditioned and unconditioned stimulus
- One pathway may be quite weak
How does LTP occur?
Evidence suggests a post-synaptic event
- Critical role of Ca
Where does the Ca come from in LTP?
Ca comes from the NMDA receptors
- Glutamate released from pre-synaptic cells acts on both AMPA and NMDA receptors in postsynaptic cell
- AMPA receptors – depolarise membrane
- NMDA receptors – depolarise a little (permeable to Ca)
What does Ca trigger in the post synaptic cell?
When Ca enters there are process that lead to an increase in number of AMPA receptors
What may cooperativity be a result of?
NMDA receptor properties
What happens to NMDA receptors when the cell is hyperpolarised?
When cell is hyperpolarised, NMDA receptor is blocked by Mg
- Voltage dependent MG block
- Even if NMDA receptors is activated by glutamate it doesn’t work much
What do NMDA receptors need to be activated fully?
NMDA receptors need to be indirectly pre-activated by a separate depolarising input
Why do you use high frequency stimulation of presynaptic neurons?
Greater depolarisation of postsynaptic membrane
What are the differences between early and late phase LTP?
Early phases - do not require protein synthesis – induction
Late phases – require protein synthesis – expression
NMDA receptor mediates an increase in?
Ca which activates calmodium kinase II
What is the role of CaMKII?
Phosphorylates a large number of other proteins
CaMKII post synaptic density?
2-5%
CaMKII structure?
Multiple catalytic subunits
What does Ca in LTP trigger in CaMKII?
Autophosphorylation and constant activation triggered by Ca in LTP
- Activated by a second messenger – Ca + calmodium
Phosphorylation enhances AMPA currents
What other kinases are involved in LTP?
PKC