TRANSIENT AND PERSISTENT INCREASES IN PROTEIN PHOSPHATASE-ACTIVITY DURING LONG-TERM DEPRESSION IN THE ADULT HIPPOCAMPUS IN-VIVO

The neural substrates of learning and memory most likely involve activ ity-dependent long-term changes in synaptic strength, including long-t erm potentiation and long-term depression.(3,18) A critical element in the cascade of events hypothesized to underlie such changes in synapt ic function is modification of protein phosphorylation.(17,28,29) Long -term depression is thought to involve decreases in protein phosphoryl ation, which could result from reduction in protein kinase activity(12 ) and/or enhancement in protein phosphatase activity.(22,23) We presen t here direct evidence that long-term depression in the hippocampus in vivo is associated with an increase in the activity of the serine/thr eonine phosphatases 1 and 2A. The increase in activity of phosphatase 1 was transient, whereas that of phosphatase 2A lasted >65 min after t he induction of long-term depression. Blockade of long-term depression prevented the observed increases in phosphatase activity, as did sele ctive inhibition of phosphatase 1 and 2A, Induction of long-term depre ssion had no effect on the level of either phosphatase, which suggests that our results reflect increases in the intrinsic activity of these two enzymes. Our findings are consistent with a model of synaptic pla sticity(16-18,22,23) that implicates protein dephosphorylation by seri ne/threonine phosphatases in the early maintenance and/or expression o f long-term depression of synaptic strength. (C) 1998 IBRO, Published by Elsevier Science Ltd.