[The role of calcineurin on the induction of synaptic plasticity].

Calcineurin is ubiquitously distributed phosphatase in the central nervous system. It has various functions, such as modulating channel properties, suppressing transmitter release, and activating transcript factors. Recently the critical role of calcineurin on synaptic plasticity, especially long-term depression, was reported, although the precise mechanism underlying LTD induction is still being debated. Calcineurin, activated by the Ca2+ influx mainly through the NMDA channel and calmodulin, dephosphorylates inhibitor-1, which suppresses PP1 activity. Thus the activation of calcineurin enhances PP1, resulting in facilitating the process leading to LTD induction. The activation of calcineurin modifies the threshold of LTP induction. A recent interesting finding is the gating mechanism from the early phase of LTP to the late phase of LTP by calcineurin activity, a process regulated by cAMP. We have reported a new type of LTD, which is suppressed by calcineurin that is dependent on group 2 mGluR receptor activity. According to the result using whole cell study with a patch pipette, including FK-506, an antagonist of calcineurin, the induction site of this LTD is presynaptic, which defers from conventional LTD. We have also discussed the involvement of murine protein tyrosine phosphatase (MPTP) in LTD induction in the hippocampal CA1 region by using an MPTP delta knockout mouse.