An Essential Role for Protein Phosphatases in Hippocampal Long-Term Depression

The effectiveness of long-term potentiation (LTP) as a mechanism for information storage would be severely limited if processes that decrease synaptic strength did not also exist. In area CA1 of the rat hippocampus, 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 okadaic acid or calyculin A, two inhibitors of protein phosphatases 1 and 2A. The loading of CA1 cells with microcystin LR, a membrane-impermeable protein phosphatase inhibitor, or calmodulin antagonists also blocked or attenuated LTD. The application of calyculin A after the induction of LTD reversed the synaptic depression, suggesting that phosphatase activity is required for the maintenance of LTD. These findings indicate that the synaptic activation of protein phosphatases plays an important role in the regulation of synaptic transmission.