# A memory transcriptome time course reveals essential long-term memory transcription factors

## TL;DR

This study identifies key transcription factors involved in long-term memory formation in fruit flies by analyzing gene activity in specific brain regions.

## Contribution

The study reveals two neuron activity-regulated transcription factors, Hr38 and sr, that are essential for long-term memory in Drosophila.

## Key findings

- A mushroom body-specific transcriptional memory trace is activated during memory consolidation in Drosophila.
- Disruption of 16 genes from the transcriptional memory trace impairs long-term memory.
- Hr38 and sr are transcription factors required for long-term memory and bind to genes in the memory trace.

## 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.

Gene expression programs underlying memory are not well understood in Drosophila. Here, authors use mushroom body-specific RNA sequencing to characterize the transcriptional trace of long-term memory and key TFs that may regulate it.