LTP

Question 1

What are the three excitatory synapses in the tri-synaptic pathway? And what NT mediates them

Answer 1

• Perforant –> Dentate granule cells
• Dentate granule –> CA3
• CA3 –> CA1
• All are glutamatergic

Question 2

What is the Schaffer collateral pathway, and what do mossy cells do?

Answer 2

• projections from the CA3 to the CA1 dendrites in the stratum radiatum
• From DG synapse to CA3 pyramidal cells

Question 3

In brief, what is the outcome of hippocampal damage / inhibition (with what?) in humans and animals in terms of LTP?

Answer 3

Humans:
- Hippocampal damage can give rise to learning and memory deficits - e.g., HM

Animals:
- Can give rise to spatial learning deficits
- NMDAR antagonist D-AP5 prevents spatial learning in animals in water maze

Question 4

What is the relationship between NMDAR-Dependent LTP and the tri-synaptic pathway?

Answer 4

• Its where they first demonstated LTP, namely at the perforant path to granule cell synapses
• Now more commonly studies at the schaffer collateral pathway between CA3 and CA1

Question 5

LTP at the CA1 region of the hippocampus has been extensively studied and shown to exist in 2 forms: an early and late-phase.

What is the difference between these?

Answer 5

Early-Phase:
- Short lasting
- Mediated primarily by changes to the postsynaptic neuron such as activation of existing receptors / alterations in receptor sensitivity

Late-phase:
- Is a form of synaptic plasticity dependent on de-novo protein synthesis!
- Protein synthesis inhibitors prevent maintenance of late-LTP from 1-4hrs onwards

Question 6

Where does the required synthesis for LTP occur? ad what does Cycloheximide do?

Answer 6

• In dendritic compartments there is translational machinery and mRNA
• Cycloheximide blocks late-LTP by inhibiting mRNA translation

Question 7

Does actinomycin D, an mRNA transcription inhibitor affect LTP? What does this mean?

Answer 7

No - so there must be mRNA present in dendrites that’s relied upon for protein synthesis

Question 8

One expression mechanism of LTP is to increase the probability and amount of neurotransmitter released. How is this done? and what are some examples / key features of these?

Answer 8

• Retrograde messenger sent form the post-synapse to the presynapse

Key features:
- Small
- Lipophilic
- Stable

Candidates:
- NO
- CO
- Arachidonic acid

Question 9

What are three things that occur to receptors in LTP

Answer 9

• Increased conductance - Increase number
• Increase the efficiency

Question 10

What is the role of CaMKII in LTP?

Answer 10

• Phosphorylates AMPA receptors leads to larger probability of activation

Question 11

How does one measure the number of post-synaptic receptors

Answer 11

• miniture EPSP happens when a single vesicle of NT is released spontaneously and activates AMPARs
• mEPSPs give an idea of quantity of AMPA receptors at a single synapse
• Bigger following LTP-like increases in postsynaptic Ca2+
• BOTOX prevents neurotransmitter vesicle release and prevent AMPA insertion