Intracellular regulation of a serotonin-gated ion channel links receptor trafficking to memory

Abstract Learning and memory arise from synaptic plasticity, the ability of neurons to modify connectivity through experience-dependent changes in receptor localisation and signalling. Here, we identify a short intracellular motif within the serotonin-gated ion channel LGC-50 that links molecular receptor dynamics to behavioural plasticity in Caenorhabditis elegans . Deletion of residues 363–379 in the intracellular M3–4 loop caused receptor clustering in intracellular compartments and abolished learning-induced redistribution without altering receptor function or immediate memory recall. Interestingly, animals expressing the truncated receptor failed to retrieve aversive memories one hour after training, revealing a role for receptor trafficking in memory stability. Combining molecular, ultrastructural and behavioural analyses in vivo , we show how intracellular receptor motifs govern experience-dependent plasticity. These findings demonstrate that precise receptor localisation and trafficking shape neural circuit adaptation and reveal a conserved mechanism by which receptor dynamics support the persistence and retrieval of memory across species.