Publication: Kramer Lab
A memory transcriptome time course reveals essential long-term memory transcription factors
Spencer G. Jones, Beatriz Gil-Martí, . . . Jamie M. Kramer, Francisco A. Martin et al
Link: https://doi.org/10.1038/s41467-025-64379-x
Published: Oct 29, 2025 Nature Communications volume 16, #9320 (2025)
Abstract: 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.
From an article in DalNews, by Dayna Park - October 31, 2025
What do fruit flies and Nobel Prizes have in common? More than you might think — especially when it comes to understanding how memories are made and stored in the brain.
Dr. Jamie Kramer, a professor in Biochemistry and Molecular Biology at Dalhousie’s Faculty of Medicine, recently co-authored a groundbreaking study accepted at Nature Communications, one of the world’s leading scientific journals.
Working with collaborators in Madrid, Spain led by Dr. Francisco Martin, Dr. Kramer’s group used fruit flies (Drosophila melanogaster) to uncover new clues about the genes and molecular switches that help memories stick.
Why fruit flies?
It might sound surprising, but fruit flies have been at the heart of genetic research for more than a century.
“They’re small, cheap, and their genetics are easy to control,” Dr. Kramer explains. “Their brains are simple enough to study in detail, but still complex enough to teach us about how memory works.”
In fact, some of the first “memory genes” were discovered in fruit flies, and research in these tiny insects has led to several Nobel Prizes—including discoveries about circadian rhythms—our daily sleep-wake cycles.
How do memories form?
Dr. Kramer’s research focuses on the difference between short-term and long-term memory. While short-term memories can fade quickly, long-term memories require a special process: certain genes in our brain cells must be switched on to help store information for the long haul.
“We know this happens in both flies and mammals, but the exact genes and transcription factors — or switches — involved have been a mystery,” says Dr. Kramer.
Using advanced technology, his team was able to isolate the specific memory-forming neurons in fruit flies and track which genes were activated as memories formed and were recalled. This was no small feat — these neurons are tiny and hard to study.
Our work could help us understand not just memory but also give clues about the mechanisms underlying the related human disorder.
The team identified a group of genes that are switched on during long-term memory formation, as well as two key “switches” (called transcription factors) that control this process. What’s especially exciting is that these switches are also linked to human neurological disorders, including some rare neurodevelopmental and neurodegenerative diseases.
“The genes that we discovered to be controlling memory storage in flies are also present in humans and implicated in human disease” Dr. Kramer notes. “That means our work could help us understand not just memory but also give clues about the mechanisms underlying the related human disorders.”
Building blocks for future research
Dr. Kramer’s work is a classic example of how basic science lays the foundation for future breakthroughs.
By mapping out how memory works in fruit flies, researchers can quickly test hundreds of genes — far faster than in using mammalian model systems.
“We’re providing the building blocks,” he says. “Other scientists can use our findngs to study these genes further.”