Protein kinase and phosphatase activity regulate the form of synaptic plasticity expressed.
Long-term potentiation (LTP) and long-term depression (LTD) are calcium-dependent forms of synaptic plasticity observed in area CA1 of the hippocampus. Low-frequency tetani (1-5 Hz) activates protein phosphatases to induce LTD, whereas high-frequency tetani (> 25 Hz) activates protein kinases to induce LTP. A tetanus at an intermediate frequency (10 Hz), however, does not result in a change in synaptic efficacy [Dudek and Bear, (1992), Proc. Natl. Acad. Sci. USA, 89:4363-4367]. We hypothesized that the 10-Hz tetanus results in no long-term change in synaptic efficacy due to a balance of the activity of protein phosphatases and protein kinases. We manipulated protein kinase/phosphatase activity at a 10-Hz tetanus to test this hypothesis. A 10-Hz tetanus under normal conditions results in a transient depression which returns to baseline in 25 min. However, inhibiting kinase activity with the protein kinase inhibitor H-7, or decreasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTD. Conversely, inhibiting phosphatase activity with the protein phosphatase inhibitor tautomycin, or increasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTP. These results suggest that the relative balance of protein kinase and phosphatase activity (and/or the calcium levels activating them) determines the expression of specific forms of synaptic plasticity, and that these forms lie on a continuum.
Coussens
C M
CM
Department of Neurobiology, Northeastern Ohio College of Medicine, Rootstown 44272, USA.
Teyler
T J
TJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium