We found that the post-translational modification of chromatin-bound proteins by polyADP-ribosylation mediates expression of long-term memory in the marine mollusk Aplysia, trained by either associative or non-associative learning. Sensitization of defensive reflexes and learning that a food is inedible are representative examples of non-associative and associative learning, respectively. For defensive reflexes, a short-term memory lasts for minutes, and long-term memory lasts days to weeks. For learning that food is inedible, a single 30 min training session causes a long-term memory maintained for 1 to 7 days. We found that PARP-1 activation is strongly correlated with long-term modifications in sensory-to-motor synapses, controlling the tail-withdrawal reflex of Aplysia. PARP-1 was activated in nuclei of sensory neurons in the pleural ganglia by stimulation causing long-term facilitation (LTF). Stimulation causing a short-term facilitation (STF) did not activate PARP-1, and long-term depression (LTD) suppressed polyADP-ribosylation in sensory neurons in the pleural ganglia. PARP-1 was similarly activated in the cerebral and buccal ganglia controlling feeding in Aplysia trained with inedible food. Moreover, treatment with 3-AB (1 mM) blocked exclusively the long-term memory of the trained Aplysia, without affecting their short-term memory. These findings are the first evidence relating the post-translational modification of nuclear proteins by polyADP-ribosylation to the formation of long-term synaptic plasticity and to behaviorally expressed long-term memory.

Keywords: polyADP-ribosylation, PARP-1, synaptic plasticity, learning and memory in trained aplysia