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

Abstract

Long-term sensitization inAplysiais 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.Aplysiareceived 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 inAplysia, but could also indicate a role for arachidonic acid in stabilizing the induction of sensitization.Significance StatementForgetting plays an essential role in memory function as both excessive and insufficient forgetting are related to profound disruptions of mental health. Our results provide preliminary evidence that the forgetting of sensitization inAplysiais a regulated process that can be delayed by blocking arachidonic acid production. This work contributes to ongoing efforts to understand the neurobiology of forgetting.