Rookie question here: In slice electrophysiology, if you’re recording from a postsynaptic neuron and you perfuse a drug, how do you determine whether the effect of the drug is directly on the postsynaptic neuron from which you’re recording or rather is due activity elicited in presynaptic neurons? As a real example, I have a compound that I think acts directly on a GPCR in a spinal neuron population, and I know that the GPCR is Gq coupled, so it should lead to some calcium increases intracellularly. I want to test this by recording from the spinal neuron and looking at the EPSC in the neuron. However, I suspect that the same GPCR might also be on the presynaptic afferents that terminate on the spinal neuron of interest. How do I exclude the presynaptic component and identify the portion of the effect that is through direct interaction with the GPCR on the postsynaptic neuron? Does adding TTX to the bath solution, to block sodium channels, allow you to say that whatever effect you record from the postsynaptic neuron is not due to presynaptic activity?
Cross-posted at ResearchGate: https://www.researchgate.net/post/How_to_determine_whether_a_drugs_effect_is_presynaptic_or_postsynaptic