A selective role of calcineurin A alpha in synaptic depotentiation in hippocampus

Pharmacological studies have suggested that long-term potentiation (LTP) an d long-term depression (LTD) and depotentiation, three forms of synaptic pl asticity in the hippocampus, require the activity of the phosphatase calcin eurin, At least two different isoforms of calcineurin are found in the cent ral nervous system. To investigate whether all of these forms of synaptic p lasticity require the same isoforms of calcineurin, we have examined LTD, d epotentiation, and LTP in mice lacking the predominant calcineurin isoform in the central nervous system, A alpha(-/-) mice. Depotentiation was abolis hed completely whereas neither LTD nor LTP were affected. These studies pro vide genetic evidence that the A alpha isoform of calcineurin is important for the reversal of LTP in the hippocampus and indicate that depotentiation and LTD operate through somewhat different molecular mechanisms.