Presynaptic protein kinase activity supports long-term potentiation at synapses between individual hippocampal neurons

Simultaneous microelectrode recording from two individual synaptically conn ected neurons enables the direct analysis of synaptic transmission and plas ticity at a minimal synaptic connection. We have recorded from pairs of CA3 pyramidal neurons in organotypic hippocampal slices to examine the propert ies of long-term potentiation (LTP) at such minimal connections. LTP in min imal connections was found to be identical to the NMDA-dependent LTP expres sed by CA3-CA1 synapses, demonstrating this system provides a good model fo r the study of the mechanisms of LTP expression. The LTP at minimal synapti c connections does not behave as a simple increase in transmitter release p robability, because the amplitude of unitary EPSCs can increase several-fol d, unlike what is observed when release probability is increased by raising extracellular calcium. Taking advantage of the relatively short axon conne cting neighboring CA3 neurons, we found it feasible to introduce pharmacolo gical agents to the interior of presynaptic terminals by injection into the presynaptic soma and have used this technique to investigate presynaptic e ffects on basal transmission and LTP. Presynaptic injection of nicotinamide reduced basal transmission, but LTP in these pairs was essentially normal. In contrast, presynaptic injection of H-7 significantly depressed LTP but not basal transmission, indicating a specific role of presynaptic protein k inases in LTP. These results demonstrate that pharmacological agents can be directly introduced into the presynaptic cell and that a purely presynapti c perturbation can alter this plasticity.