RT Journal Article T1 A memory transcriptome time course reveals essential long-term memory transcription factors A1 Jones, Spencer G. A1 Gil Martí, Beatriz A1 Sacristán Horcajada, Eva A1 Edison, Abigail C. A1 Butler, Emily F. A1 Miandashti, Neda A1 Roselli, Camilla A1 Turiégano, Enrique A1 Boto, Tamara A1 Kramer, Jamie M. A1 Martín Castro, Francisco Antonio AB Long-term memory (LTM) requires transcription and translation of new proteins, yet the transcriptional control of memory remains poorly understood. Here, we performed a transcriptome time-course during LTM formation in Drosophila melanogaster exposed to courtship conditioning. We identified a mushroom body-specific transcriptional memory trace that becomes activated during memory consolidation. Using scRNAseq of CREB-activated cells we were able to detect a persistent transcriptional response in MB neurons after LTM consolidation and retrieval. As a proof of causality, we conducted a loss-of-function screen for genes comprising the transcriptional memory trace, finding 16 positive hits whose disruption impaired LTM. Among them, we identified two neuron activity-regulated genes, Hr38 and sr, which encode transcription factors that are activated by courtship LTM training, required for LTM, and bind to many genes comprising the transcriptional memory trace. Overall, we further define the transcriptional response to LTM and identify transcription factors that may help shape it. PB Springer nature SN 2041-1723 YR 2025 FD 2025-10 LK https://hdl.handle.net/20.500.14352/126505 UL https://hdl.handle.net/20.500.14352/126505 LA eng NO Jones, S.G., Gil-Martí, B., Sacristán-Horcajada, E. et al. A memory transcriptome time course reveals essential long-term memory transcription factors. Nat Commun 16, 9320 (2025). https://doi.org/10.1038/s41467-025-64379-x NO EASI-Genomics - This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110. Part of the next-generation sequencing (NGS) data analysis was provided by the Genomics and NGS Core Facility at the Centro de Biología Molecular Severo Ochoa (CBMSO, CSIC-UAM) which is part of the CEI UAM + CSIC, Madrid, Spain-http://www.cbm.uam.es/genomica/. FAM was a recipient of a RyC-2014-14961 contract (2016-2022). Grant RyC-2014-14961 (FAM) funded by MICIU/AEI/10.13039/501100011033 and by ESF Investing in your future. Grant CNS2022-135223 (FAM) funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGeneration EU/PRTR. Grant PID2022-142742NB-I00 (FAM) funded by MICIU/AEI/10.13039/501100011033 and by EDFR/EU. BG-M is a recipient of a FPI-UAM predoctoral fellowship, grant number SFPI/2020/00878. This project was also funded by a Project Grant (#363723) from the Canadian Institutes of Health Research to JMK and a Nova Scotia Graduate Scholarship to SGJ. NO European Commission NO Ministerio de Ciencia e Innovación (España) NO Universidad Autónoma de Madrid NO Canadian Institutes of Health Research NO Dalhousie University DS Docta Complutense RD 18 mar 2026