Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase, calcineurin, on induction of long-term potentiation in rat visual cortex.

A role of Ca2+/calmodulin-dependent protein phosphatase (calcineurin) in induction of long-term potentiation (LTP) was investigated using its selective inhibitor, FK506, in visual cortical slices of young rats. Field potentials or excitatory postsynaptic potentials (EPSPs) to test stimulation of white matter were recorded extra- or intracellularly from layer 2/3, and tetanic stimulation (tetanus) was applied to the white matter at 5 Hz. During the application of FK506 (1 microM), short tetanus (6 s) which had rarely induced LTP in the normal medium, became effective in inducing LTP. Tetanus for 1 min in the presence of FK506 induced LTP with higher probability than in the normal medium. To test possible involvement of presynaptic mechanisms, paired pulses at 50 ms intervals were given to the white matter. The facilitation ratio of the second to first EPSPs was not significantly changed by FK506 and after the induction of LTP, suggesting that the action of FK506 may not be presynaptic. To confirm this, FK506 was injected directly into neurons through recording electrodes. In cases in which stable EPSPs were recorded, the probability of LTP induction became higher than that obtained with normal electrodes. These results suggest that calcineurin plays a role in processes antagonizing the induction of LTP in visual cortex.