Long-term heterosynaptic inhibition in Aplysia

Abstract

Synaptic transmission between mechanosensory and motor neurons of the gill withdrawal reflex in Aplysia can undergo both short-term^1,2 and long-term^3,4 modulation. One form of short-term synaptic depression lasting minutes can be evoked by the peptide Phe-Met-Arg-Phe-amide (FMRFamide)^5–8, and is mediated by the lipoxygenase pathway of arachidonic acid⁷. We report here using cell culture⁹, that the same monosynaptic sensory-to-motor component of the gill withdrawal reflex can also undergo long-term synaptic depression lasting 24 h after five applications of FMRFamide over a 2-h period. The long-term depression evoked by FMRFamide is transmitter-specific. Dopamine or low-frequency stimulation of sensory neurons, which also produce short-lasting synaptic depression in vivo^1,5, failed to evoke a long-term change. As is the case for long-term presynaptic facilitation of this connection with serotonin¹⁰, the long-term depression, but not the short-term, can be blocked when applications of FMRFamide are given in the presence of anisomycin, a reversible inhibitor of protein synthesis. Thus, heterosynaptic depression parallels heterosynaptic facilitation in having a long-term as well as a short-term form, and in both cases the long-term modulation requires the synthesis of gene products not essential for the short-term changes.