Long-term potentiation Flashcards
How can LTP be induced?
Through large stimulation (ie memory or tetnus)
What are the NMDAR dependent LTP pathways in the tri-synaptic pathway of the hippocampus?
and which is the pathway that is NON-NMDAR dependent
- Perforrant fiber pathway (synapses onto dentate reigon)
- Schaefferr collateral fiber pathway (CA3 to CA1)
Does NOT require NDMA activation for potentiation
- Mossy fiber pathway (dentate to CA3)
What are the properties of NMDAR-dependent LTP at CA3- CA1 synapses?
- Intracellular rise in Ca2+ through NMDA activation is necessary for LTP
- Persistance of LTP at these synapses (aka late-LTP) is dependent on de novo protein synthesis in the dendrites (ie locally)
What properties of NMDARs allow them to act as coincidence detectors?
The Mg ions sit inside the NMDAR pore preventing Na influx and K efflux
Since AMPAR dont have this, they are opened with glutamate and only when the opening of these receptors causes sufficient depolarisation does the Mg lift out of NMDAR and open the channels-> means they need HIGH freq stimulation (j like LTP needs)
What presynaptic mechanisms allow for long-term changes in synaptic efficacy and the evidence for such changes?
- increased probability of NT release
- incresed amount of NT release
- Retrograde transmitter (small lipophillic molecule eg NO, CO, AA)
Expression is through NMDA, modulation through AMPA
need a retrograde transmitter because post snyaptic NMDA transmisson is necessary for LTP- so presynaptic changes would need to be signalled by the post-synapse to the pre-synapse
What postsynaptic mechanisms allow for long-term changes in synaptic efficacy and the evidence for such changes?
Increase efficency of post-synaptic receptors
- phosphorylating AMPA can lead to larger current generation or greater probability of channel opening)
Increase number of post-synaptic receptors
- via phosphorylation-mediated insertion of AMPAR
- new synthesis of AMPAR
- This would increase the number of functioning synapses
Increase conductance of post-synaptic receptors
- known that post-induction, post synaptic change there is an inc in flux of ions from outside to inside
Evidence: mini synaptic currents measure amplitude of AMPAR activation in response to just one vesicle of Glu release, when you give high stimulus (eg tetnus) there is greater Ca2+ current in response to same Glu release: evidence that either the efficency of AMPA was increased or the number of AMPA was increased
Evidence: recordings from previously silent synapses (ie only had NMDAR), and apply tetnus and then see activity; shows that insertion of AMPAR into membrane post LTP. can further test this by inhibiting membrane fusion and see if it inhibits LTP (it does)
Expression is through NMDA, modulation through AMPA
What does D-AP5 administration show?
It is an NMDAR antagonist, and it blocks the ability for tetnus (100 Hz aka intense stimulus) to induce LTP: shows that NMDARs are needed for LTP
What are miniture synaptic currents?
Why is protein synthesis important for late-LTP? Whats the evidence?
Late-LTP is form of synaptic plasticity: thus de novo protein synthesis is needed, esp if LTP is meant to be how memories are made and stored
- blocking protein synthesis with translation (anisomycin) and transcription (actinomycin) inhibitors blocked LTP (blocked maintenance from 1-4 hrs onwards)
Translation is most important (can make protiens from existing mRNA) and occurs in dendrites
- Went into hippocampus and physically seperated CA1 bodies from dendrites, and generated LTP with large stimulus -> showed that protein synthesis occured locally (mRNA in the dendrites not soma)
- Only inhibition of translation and not transcription blocked LTP-> bc DNA is in the soma
Why is CaMKII a key kinase in LTP?
CaMKII 1. phosphoryltes AMPAR 2. mediates AMPAR insertion into membrane and 3. promotes synthesis of new AMPARs
Inhibiting CaMKII with a peptide inhibits LTP
