Alterations in the Balance of Protein Kinase/Phosphatase Activities Parallel Reduced Synaptic Strength During Aging

Norris, Christopher M., Shelley Halpain, and Thomas C. Foster. Alterations in the balance of protein kinase/phosphatase activities parallel reduced synaptic strength during aging. J. Neurophysiol. 80: 1567–1570, 1998. 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 μM) 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 μM) 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 μM) 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.