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

Area of Science:

• Neuroscience
• Molecular Biology
• Proteomics

Background:

• Long-term memory (LTM) formation requires new protein synthesis, but the specific proteins involved are not fully understood.
• The pond snail, *Lymnaea stagnalis*, offers a model system to investigate LTM mechanisms.

Purpose of the Study:

• To identify proteins critical for LTM formation using a transcriptome-guided proteomic approach.
• To understand the molecular mechanisms underlying LTM in *Lymnaea stagnalis*.

Main Methods:

• Aversive operant conditioning was used to induce LTM in *Lymnaea stagnalis*.
• Transcriptome-guided proteomic analysis was performed on the central nervous system (CNS) of animals with and without LTM, and controls.
• Differentially expressed proteins were identified and functionally annotated.

Main Results:

• 366 differentially expressed proteins were linked to LTM formation.
• 88 proteins were upregulated and 36 downregulated in LTM compared to controls.
• Proteins involved in proteasome activity and translation initiation, including EIF2D, were upregulated, suggesting a balance between protein synthesis and degradation is vital for LTM.

Conclusions:

• This study provides the first transcriptome-guided proteomic analysis of LTM formation in *Lymnaea stagnalis*.
• The findings highlight the importance of protein synthesis and degradation balance for LTM.
• Nuclear factor Y is implicated as a potential regulator of LTM-related transcription, paving the way for identifying mammalian LTM orthologs.