I am looking for a reliable and powerful compound to validate a positive effect enhancing LTP in Schaffer collateral-CA1 experiments (rat hippocampal slices).
I am performing both E-LTP (HFS 100 Hz, 20 stimulations) and L-LTP (4 times HFS 100 Hz, 100 stimulations) experiments at room temperature. However, so far I could not find a compound clearly increasing LTP. I have used nicotine 100 µM and an alpha 7 nAChR agonist. I put the compound half hour before HFS, and wash-out half hour after. However, the slices in presence of the compounds do not seem to be different from the controls.
Forskolin treatment of hippocampal slices are known to activate the PKA pathway and thus induce LTP in slices which is quite robust and stable. just 15 min treatment of forskolin is sufficient to induce LTP in slices even in the absence of an accompanying HFS or other relevant stimulation protocol.
Similarly, just BDNF treatment of slices also induces LTP in hippocampal CA3-CA1 synapses.
Both your E-LTP and L-LTP protocols alone should have given you good LTP increase if all other conditions and criteria are maintained proper.
I have tried a number of different stimulation protocols including HFS and TBS also. When I use HFS protocol, I use a train of 100 stimuli delivered at 100 Hz. For E-LTP, one such train is used. For L-LTP, four such trains spaced at either 20 sec or 5 min spacing have given me good extent of LTP induced in CA3-CA1 synapses.
Kaushik, thank you very much your answer.
I have already tried forskolin for the induction of chemical LTP, which worked fine. Moreover, my early LTP (induced by 1 train of 20 stimulations at 100 Hz) and late LTP (induced by 4 trains of 100 stimulations at 100 Hz, each train separated by 5 min) protocols are well validated and induced LTP (see attached figure).
My question is more focused onto which compound can I use as a positive control for these already established forms of LTP? For example, if my E-LTP after one hour induces a potentiation of around 120%... do you know any substance which would reliable increase these early and/or late LTP (without affecting the preHFS baseline levels)?
I have tried nicotine 100 µM and an alpha7 nAChR partial agonist. I also tried some phosphodiesterase inhibitors. But so far I could not see an effect increasing the previous LTP levels with any of them.
So the question is open. Any compound which reliable enhances HFS-induced LTP without affecting the baseline?
Again, thank you very much Kaushik for your contribution!
So if I have understood correctly, you intent to use a drug that by itself alone does not have any effect but in the presence of suitable LTP induction protocol, is able to cause enhancement of LTP.
Phosphodiesterase PDE4 inhibitors such as Rolipram and Ro-20-1724 are some drugs that by blocking PDE activity cause enhancement of LTP by normal LTP stimulation protocols. Also, as far as I remember, they have no effect on baseline activity. May be you can try these drugs too and verify for yourself in your experiments.
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