Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila

Mai Takakura,Yukinori Hirano,Hiroyuki Okuno,Yoko Kimura,Reiko Nakagawa,Takeshi Ota,Abdalla G Alia,Man Yung Ng

doi:10.1038/s41467-021-20898-x

Abstract

Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state.

Highlights

Consolidated memory can be preserved or updated depending on the environmental change
Given that acetylation of CoRest-C is reversed by Rpd[3], resulting in its dissociation from Rpd[3], the acetylation of CoRest-C could act as a temporal gating mechanism for activitydependent transcription
This suggests that opening and closing the temporal gate for activity-dependent transcription through Rpd3/CoRest is important for memory consolidation and behavioral flexibility, respectively, and proposes the model in which the molecular mechanism acting in memory consolidation could affect the later memory updating by controlling the memory state

Summary

Introduction

Consolidated memory can be preserved or updated depending on the environmental change. We discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd[3] and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. The consolidated form of memory is not completely fixed, but depending on environmental changes, animals can either update or preserve their consolidated memory This conflicting nature of memory has been linked to behavioral flexibility, the dysfunction of which is related to the autism spectrum disorder[1,2]. Previous studies have revealed the molecular and neuronal mechanisms that are activated when memory is updated[3,4,5], it may be possible that the initial memory consolidation event has already determined the flexibility of memory for later updating. Similar to HDAC2 knockout which enhances fear memory[22], the knockdown of HDAC2 homolog, reduced potassium dependency

Methods

Results

Conclusion