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

Aug 2026 · iScience · Vol 29 · 0 citations · 73 references
Medicine

TL;DR

It is shown how intracellular receptor motifs govern experience-dependent plasticity and shape neural circuit adaptation and reveal a conserved mechanism by which receptor dynamics support the persistence and retrieval of memory across species.

Abstract

Summary 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.

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