Presynaptic and postsynaptic Ca 2+ and CamKII contribute to long-term potentiation at synapses between individual CA3 neurons

Abstract

Long-term potentiation (LTP) in the Schaffer collateral pathway from the CA3 to the CA1 region of the hippocampus is thought to involve postsynaptic mechanisms including Ca(2+)- and CamKII-dependent alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor insertion. However, very little is known about possible presynaptic mechanisms. It is easier to address that question at synapses between individual neurons in the CA3 region, where both sides of the synapses are accessible to substances injected into the cell bodies. Previous studies using that method showed that CA3-CA3 LTP involves presynaptic protein kinases as well as postsynaptic receptor insertion. We have extended those findings by exploring the pre- and postsynaptic roles of Ca(2+) and CamKII, and we have also compared results with two induction protocols, 1-Hz-paired and -burst-paired, which may involve pre- and/or postsynaptic mechanisms in addition to receptor insertion in CA1. Similar to results in CA1, we find that CA3-CA3 LTP completely depends on postsynaptic Ca(2+) with the 1-Hz-paired protocol but depends only partially on postsynaptic Ca(2+) or CamKII with the -burst-paired protocol. Potentiation with that protocol also partially depends on presynaptic Ca(2+) or CamKII, suggesting that the additional mechanisms of potentiation, at least in part, are presynaptic. Furthermore, the pre- and postsynaptic mechanisms seem to act in series, suggesting coordinate regulation of the two sides of the synapses. CA3-CA3 LTP with the 1-Hz-paired protocol also partially depends on presynaptic Ca(2+), suggesting that it may involve presynaptic mechanisms as well.