Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization in Aplysia

Abstract

Long-term sensitization in Aplysia is accompanied by a persistent up-regulation of mRNA encoding the peptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa), a neuromodulator that opposes the expression of sensitization through activation of the arachidonic-acid second-messenger pathway. We completed a pre-registered test of the hypothesis that FMRFa plays a critical role in the forgetting of sensitization. Aplysia received long-term sensitization training and were then given whole-body injections of vehicle (N = 27), FMRFa (N = 26), or 4-bromophenacylbromide (4-BPB; N = 31), a phospholipase inhibitor that prevents the release of arachidonic acid. FMRFa produced no changes in forgetting. 4-BPB decreased forgetting measured 6 days after training (ds = 0.55 95% CI[0.01, 1.09]), though the estimated effect size is uncertain. Our results provide preliminary evidence that forgetting of sensitization may be a regulated, active process in Aplysia. s