Role of protein synthesis in the transition from synaptic short-term to long-term depression in neurons of Helix pomatia.

Abstract

The time course of the formation of synaptic long-term depression was analysed in neurons of Helix pomatia. Polysynaptic excitatory postsynaptic potentials were evoked in identified neurons by stimulation of the right pallial nerve. First, synaptic depression was observed during four consecutive series of excitatory postsynaptic potentials spaced by either 2, 10 or 60 min in the presence and absence of compounds inhibiting protein synthesis. Inhibition of RNA translation (but not of transcription) reduced the increasing depression of series spaced by 10 and 60 min but not by 2 min. This demonstration of translation-dependent depression present only 10 min after a previous excitatory postsynaptic potential series was analysed further by observations of the time course of excitatory postsynaptic potential recovery from short-term depression in experiments with intact versus inhibited protein synthesis. When synthesis was inhibited, recovery occurred along a double-exponential trajectory. However, when synthesis was intact, the exponential recovery was interrupted discontinuously 6-10 min after a series of excitatory postsynaptic potentials by the onset of a spontaneous and increasing depression lasting for at least 12 h. Puromycin, anisomycin and actinomycin D were used as inhibitors not affecting the short-term properties of excitatory postsynaptic potentials. Experiments with camptothecin, on the other hand, revealed that this inhibitor enhanced excitatory postsynaptic potential amplitudes and reduced their short-term depression. It is concluded that long-term depression, depending upon de novo protein synthesis, was initiated only 10 min after a series of excitatory postsynaptic potentials. Evidence was obtained indicating that this early initiated protein synthesis circumvented the transcription processes within the cell nuclei.