Distinct Proteomic Brain States Underlying Long-Term Memory Formation in Aversive Operant Conditioning

Long-term memory (LTM) formation relies on de
novo protein synthesis; however, the full complement of proteins
crucial
to LTM formation remains unknown in any system. Using an aversive
operant conditioning model of aerial respiratory behavior in the pond
snail mollusk, Lymnaea stagnalis (L. stagnalis), we conducted a transcriptome-guided proteomic analysis on the
central nervous system (CNS) of LTM, no LTM, and control animals.
We identified 366 differentially expressed proteins linked to LTM
formation, with 88 upregulated and 36 downregulated in LTM compared
to both no LTM and controls. Functional annotation highlighted the
importance of balancing protein synthesis and degradation for LTM,
as indicated by the upregulation of proteins involved in proteasome
activity and translation initiation, including EIF2D, mRNA levels
of which were confirmed to be upregulated by conditioning and implicated
nuclear factor Y as a potential regulator of LTM-related transcription
in this model. This study represents the first transcriptome-guided
proteomic analysis of LTM formation ability in this model and lays
the groundwork for discovering orthologous proteins critical to LTM
in mammals.