GENETIC AND PHARMACOLOGICAL EVIDENCE FOR A NOVEL, INTERMEDIATE PHASE OF LONG-TERM POTENTIATION SUPPRESSED BY CALCINEURIN

To investigate the role of phosphatases in synaptic plasticity using g enetic approaches, we generated transgenic mice that overexpress a tru ncated form of calcineurin under the control of the CaMKII alpha promo ter. Mice expressing this transgene show increased calcium-dependent p hosphatase activity in the hippocampus. Physiological studies of these mice and parallel pharmacological experiments in wild-type mice revea l a novel, intermediate phase of LTP (I-LTP) in the CA1 region of the hippocampus. This intermediate phase differs from E-LTP by requiring m ultiple trains for induction and in being dependent on PKA. It differs from L-LTP in not requiring new protein synthesis. These data suggest that calcineurin acts as an inhibitory constraint on I-LTP that is re lieved by PKA. This inhibitory constraint acts as a gate to regulate t he synaptic induction of L-LTP.