Genetic and pharmacological evidence for a novel, intermediate phase of long-term potentiation suppressed by calcineurin.

Winder DG, Mansuy IM, Osman M, Moallem TM, Kandel ER
Cell. 1998 92 (1): 25-37

PMID: 9489697 · DOI:10.1016/s0092-8674(00)80896-x

To investigate the role of phosphatases in synaptic plasticity using genetic approaches, we generated transgenic mice that overexpress a truncated form of calcineurin under the control of the CaMKIIalpha promoter. Mice expressing this transgene show increased calcium-dependent phosphatase activity in the hippocampus. Physiological studies of these mice and parallel pharmacological experiments in wild-type mice reveal a novel, intermediate phase of LTP (I-LTP) in the CA1 region of the hippocampus. This intermediate phase differs from E-LTP by requiring multiple 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 relieved by PKA. This inhibitory constraint acts as a gate to regulate the synaptic induction of L-LTP.

MeSH Terms (28)

Action Potentials Animals Calcineurin Cyclic AMP-Dependent Protein Kinases Electric Stimulation Enzyme Inhibitors Excitatory Postsynaptic Potentials Female Gene Expression Gene Expression Regulation Genetic Engineering Hippocampus Long-Term Potentiation Male Mice Mice, Inbred CBA Mice, Mutant Strains Mice, Transgenic Phosphoprotein Phosphatases Phosphoric Monoester Hydrolases Protein Biosynthesis Proteins Pyramidal Cells Recombinant Proteins Stimulation, Chemical Synapses Synaptic Transmission Transgenes

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