"Silent" metaplasticity of the late phase of long-term potentiation requires protein phosphatases.
The late phase of long-term potentiation (L-LTP) is correlated with some types of long-term memory, but the mechanisms by which L-LTP is modulated by prior synaptic activity are undefined. Activation of protein phosphatases by low-frequency stimulation (LFS) given before induction of L-LTP may significantly modify L-LTP. Using cellular electrophysiological recording methods in mouse hippocampal slices, we show that LFS given before induction of L-LTP inhibited L-LTP in an activity-dependent manner without affecting either basal synaptic strength or the early phase of LTP (E-LTP). This anterograde inhibitory effect of LFS was persistent, required N-methyl-D-aspartate (NMDA) receptor activation, and was blocked by inhibitors of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). These data indicate that certain patterns of LFS can activate PP1 and/or PP2A, and that long-lasting activation of these phosphatases by prior LFS can suppress the subsequent expression of L-LTP without affecting E-LTP. Because this inhibition of L-LTP is caused by prior synaptic activity that, alone, produced no net effect on synaptic efficacy, we suggest that this is a "silent" form of metaplasticity that may influence long-term information storage by modulating the capacity of synapses to express L-LTP after repeated bouts of activity.
Woo
Newton H
NH
Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, Canada.
Nguyen
Peter V
PV
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D009435:Synaptic Transmission; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2