The Role of Transcription and Chromatin in Making Long-Term Memories
Date
2023-08-17
Authors
Jones, Spencer G.
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Abstract
Long-term memory (LTM) requires transcription and accessible chromatin for formation, however, the genes that are activated and how they promote LTM remains unclear. Here, we profiled the memory transcriptome induced in memory-associated mushroom body (MB) nuclei of Drosophila melanogaster at eight time-points during and after courtship memory training. We identify a transcriptional program that becomes activated in the MB as training progresses, enriched for genes in metabolism and known memory signaling pathways, and is distinct from whole-head tissue. Among MB training induced genes, we identified two known insect activity-regulated genes, Hr38 and stripe (sr). We tested Hr38 and sr for a role in courtship memory following adult-specific knockdown and found that they are required in the MB specifically for LTM formation, with no impact on short-term memory. Further, we show that Hr38 and sr have highly accessible chromatin in the MB at CrebB binding sites, suggesting they are downstream targets of CrebB during LTM formation. To identify what genes could be regulated downstream of Hr38 and sr, we used publicly available binding site information and contrasted this with our memory transcriptome. We find that sr may regulate the later MB-specific transcriptional program that occurs when memory consolidation is thought to occur. Our research demonstrates that the SWI/SNF chromatin remodelling complex is required for LTM-associated gene expression and chromatin accessibility changes that occur following memory training, and that this occurs downstream of Hr38 and sr. Finally, we show that disrupting the SWI/SNF complex during LTM results in a near-complete loss of inducible expression of genes with known memory-related functions, highlighting the direct and indirect role SWI/SNF plays in establishing LTM. Collectively, this work provides an invaluable resource of transcription and chromatin regulation during LTM formation for the scientific community, and together with the first mechanistic information about the SWI/SNF complex during acute memory processes, has important implications for understanding processes crucial to cognition in health and disease.
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Keywords
Long-term memory, Transcriptional regulation, Chromatin remodeling, SWI/SNF complex, Drosophila melanogaster