AN ESSENTIAL ROLE FOR PROTEIN PHOSPHATASES IN HIPPOCAMPAL LONG-TERM DEPRESSION

The effectiveness of long-term potentiation (LTP) as a mechanism for i nformation storage would be severely limited if processes that decreas e synaptic strength did not also exist. In area CA1 of the rat hippoca mpus, prolonged periods of low-frequency afferent stimulation elicit a long-term depression (LTD) that is specific to the stimulated input. The induction of LTD was blocked by the extracellular application of o kadaic acid or calyculin A, two inhibitors of protein phosphatases 1 a nd 2A. The loading of CA1 cells with microcystin LR, a membrane-imperm eable protein phosphatase inhibitor, or calmodulin antagonists also bl ocked or attenuated LTD. The application of calyculin A after the indu ction of LTD reversed the synaptic depression, suggesting that phospha tase activity is required for the maintenance of LTD. These findings i ndicate that the synaptic activation of protein phosphatases plays an important role in the regulation of synaptic transmission.