LAUSR

ABSTRACT For several decades, the ability of protein synthesis inhibitors (PSI) to suppress the long‐term potentiation (LTP) of hippocampal responses is known. It is considered that mechanisms of such impairment are related to a cessation of translation and a delayed depletion of the protein pool required for maintenance of synaptic plasticity. The present study demonstrates that cycloheximide or anisomycin applications reduce amplitudes of the field excitatory postsynaptic potentials as well as the presynaptically mediated form of plasticity, the paired‐pulse facilitation after LTP induction in neurons of the CA1 area of hippocampus. We showed that nitric oxide signaling could be one of the pathways that cause the LTP decrease induced by cycloheximide or anisomycin. Inhibitor of the NO synthase, L‐NNA or the NO scavenger, PTIO, rescued the late‐phase LTP and restored the paired‐pulse facilitation up to the control levels. For the first time we have directly measured the nitric oxide production induced by application of the translation blockers in hippocampal neurons using the NO‐sensitive dye DAF‐FM. Inhibitory analysis demonstrated that changes during protein synthesis blockade downstream the NO signaling cascade are cGMP‐independent and apparently are implemented through degradation of target proteins. Prolonged application of the NO donor SNAP impaired the LTP maintenance in the same manner as PSI. HIGHLIGHTSApplication of the protein synthesis inhibitors led to impairment of the LTP and the NO production increase in the brain slices.Inhibition of the NO functioning rescued the late‐phase LTP impaired by the PSI.Action of PSI on LTP was cGMP‐independent and involved activation of the proteasome complex.Exogenous NO donor partially simulated impairment of LTP by the PSI.