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 it s selective inhibitor, FK506, in visual cortical slices of young rats. Field potentials or excitatory postsynaptic potentials (EPSPs) to tes t stimulation of white matter were recorded extra- or intracellularly from layer 2/3, and tetanic stimulation (tetanus) was applied to the w hite matter at 5 Hz. During the application of FK506 (1 mu M), Short t etanus (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 tes t 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 no t be presynaptic. To confirm this, FK506 was injected directly into ne urons through recording electrodes. In cases in which stable EPSPs wer e recorded, the probability of LTP induction became higher than that o btained with normal electrodes. These results suggest that calcineurin plays a role in processes antagonizing the induction of LTP in visual cortex.