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

Learning and memory arise from synaptic plasticity, the ability of neurons to modify connectivity through experience-dependent changes in receptor localization and signaling. Here, we identify a short intracellular motif within the serotonin-gated ion channel LGC-50 that links molecular receptor dynamics to behavioral 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 displayed impaired retrieval of aversive memories 1 h after training, revealing a role for receptor trafficking in memory stability. Combining molecular, ultrastructural, and behavioral analyses in vivo, we show how intracellular receptor motifs govern experience-dependent plasticity. These findings demonstrate that precise receptor localization and trafficking shape neural circuit adaptation and reveal a conserved mechanism by which receptor dynamics support the persistence and retrieval of memory across species.