Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases.
In the CA1 region of adult guinea pig hippocampal slices, long trains of theta frequency (5 Hz) stimulation produced a small enhancement of basal synaptic transmission but depressed the strength of synaptic transmission at synapses that had recently undergone long-term potentiation (LTP). Five hertz stimulation delivered immediately prior to high-frequency stimulation also inhibited the subsequent induction of LTP. The depression of potentiated synapses by 5 Hz stimulation (depotentiation) was blocked by 2-amino-5-phosphonovalerate and was observed only during the early phases of LTP. Furthermore, the protein phosphatase inhibitors okadaic acid and calyculin A blocked both depotentiation and the ability of 5 Hz stimulation to inhibit subsequent LTP, suggesting that protein phosphatases are involved in the ability of 5 Hz stimulation to modulate synaptic plasticity in the CA1 region of the hippocampus.
O'Dell
T J
TJ
Howard Hughes Medical Institute,Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Kandel
E R
ER
D000818:Animals; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D010749:Phosphoprotein Phosphatases