Alterations in the balance of protein kinase/phosphatase activities parallel reduced synaptic strength during aging

The current research examined the regulation of synaptic strength by protein phosphorylation during aging. Bath application of the protein phosphatase 1 and 2A (PP1 and PP2A) inhibitor calyculin A (1 mu M) enhanced CA3-CA1 synaptic strength in hippocampal slices from aged male (20-24 mo) but not from young adult male (4-6 mo) Fischer 344 rats. Similarly, injection of the PP1 and PP2A inhibitor microcystin-L,R (5 mu M) into CA1 cells caused an increase in the intracellular synaptic response only in slices from aged rats. In contrast, bath application of the serine/threonine kinase inhibitor H-7 (10 mu M) induced a decrease in synaptic strength only in slices from the young adult group. These results demonstrate that phosphorylation-dependent regulation of intrinsic synaptic efficacy changes during aging.