Learning and memory II Flashcards
What did Donald Hebb propose?
That memories start in SYNAPSES:
- The COORDINATED activity of a presynaptic terminal and a postsynaptic neuron STRENGTHENS the connection between them
Where was Hebb’s hypothesis tested?
Why?
In the hippocampus
The hippocampus is involved in memory
What 2 things can change the hippocampus?
- London taxi drivers - bigger hippocampus
- Neurodegenerative diseases attack the hippocampus early
What is the simplified circuit of the hippocampus?
- Input
- Dentate gyrus
- CA3
- CA1
- Output via fornix and subiculum
What are CA3 cells aka?
Mossy fibres
What are the connections between CA3 and CA3 aka?
Schaffer collaterals
Which synapase is used to study the mechanisms of LTD and LTP?
The synapse between CA3 and CA1 neurons in the HIPPOCAMPUS
What happens when the CA3 is electrically stimulated?
There is production of an EPSP in CA1
What happens when the CA3 is electrically stimulated with HIGH FREQUENCY stimulation?
What is this called?
There is an increase in the amplitude of EPSPs
This is called long-term potentiation (LTP)
What properties does LTP show?
1) Input specificity
2) Co-operativity (co-incidence) which doesn’t require high frequency stimulation
How does LTP show input specificity?
What does this also show?
Neuron with 2 inputs from different neurons will only increase in EPSP amplitude in synapse 1 if ONLY stimulate synapse 1 with HFS
Synapse 2 is unaffected
Shows the mechanism of LTP to be confined to the synapses and NOT the cell bodies
How does LTP show co-incidence without HFS?
- Can depolarise both pre- and post- synaptic neurons at the SAME time
- This will cause the synapse to undergo LTP
What does the mechanism of co-incidence without HFS suggest?
A mechanism of associative learning:
- One pathway is the unconditioned stimulus (CA3)
- CA3 synapses on CA1
- CA1 regulates response (conditioned stimulus)
- If activate both neurons at the same time (US and CS) –> strengthen the synapse
- Can then use the conditioned stimulus to evoke the response
- CA1 can trigger response without CA3
What are the 2 different ideas about how LTP could occur?
Which one has more evidence?
1) By pre-synaptic changes (proteins change number or properties)
2) By a postsynaptic event
- -> More evidence!!
What substance is important in triggering LTP?
How?
Ca2+:
Ca2+ though NDMA receptors is activated by the binding of GLUTAMATE, which is released from the presynaptic membrane
What occurs in the NDMA receptors when the cell is hyperpolarised?
Mg2+ block in the pore of the channel
What happens when the NDMA receptors are activated with glutamate, when they are blocked with Mg2+?
The channels don’t open much
How is the Mg2+ block removed from the NDMA receptor?
How does this trigger LTP?
When activating the NDMA receptor with glutamate AT THE SAME TIME AS depolarising the membrane
Triggers LTP as as Ca2+ can enter through the NDMA receptor
Ca2+ is the key trigger of LTP (by increasing the number of AMPA receptors in the presynaptic membrane)
How does subsequent depolarisation of both the pre- and post synaptic neuron cause simultaneous activation?
Causes release of glutamate from the presynaptic neuron
AND
Removal of the Mg2+ block from the postsynaptic neuron due depolarisation
How does high frequency stimulation cause LTP?
- Depolarises the membrane of the postsynaptic neuron much stronger due to SUMMATION of EPSPs
- Reach depolarisation threshold this is sufficient enough to remove the Mg2+ block
What are the differences between EARLY and LATE LTP?
Early:
- No protein synthesis
- ‘LTP induction’
Late:
- Protein synthesis
- ‘Expression of LTP’
How does Ca2+ mediated entry induce early phase LTP?
Activates calmodulin kinase II (CaMKII), which phosphorylates other proteins, leading to enhances AMPA currents
Where is CaMKII present?
In the post synaptic density
What is the structure of CaMKII?
2 different subunits - regulatory and catalytic
