Distinct Proteomic\nBrain States Underlying Long-Term\nMemory Formation in Aversive Operant Conditioning

Long-term memory (LTM) formation relies on <i>de\nnovo</i> protein synthesis; however, the full complement of proteins\ncrucial\nto LTM formation remains unknown in any system. Using an aversive\noperant conditioning model of aerial respiratory behavior in the pond\nsnail mollusk, <i>Lymnaea stagnalis</i> (<i>L. stagnalis</i>), we conducted a transcriptome-guided proteomic analysis on the\ncentral nervous system (CNS) of LTM, no LTM, and control animals.\nWe identified 366 differentially expressed proteins linked to LTM\nformation, with 88 upregulated and 36 downregulated in LTM compared\nto both no LTM and controls. Functional annotation highlighted the\nimportance of balancing protein synthesis and degradation for LTM,\nas indicated by the upregulation of proteins involved in proteasome\nactivity and translation initiation, including EIF2D, mRNA levels\nof which were confirmed to be upregulated by conditioning and implicated\nnuclear factor Y as a potential regulator of LTM-related transcription\nin this model. This study represents the first transcriptome-guided\nproteomic analysis of LTM formation ability in this model and lays\nthe groundwork for discovering orthologous proteins critical to LTM\nin mammals.