Extinction Training Suppresses Activity of Fear Memory Ensembles across the Hippocampus and Alters Transcriptomes of Fear-encoding Cells

• NCJ Number: 309480
• Author(s): Alfredo Zuniga; Jiawei Han; Isaac Miller-Crews; Laura A. Agee; Hans A. Hofmann; Michael R. Drew
• Date Published: June 2024
• Grant Number(s): 2019-R2-CX-0049
• Agencies: NIJ-Sponsored

Annotation

This article describes the authors’ testing of whether extinction is enough to suppress the reactivation of “fear ensemble” cells in other regions for the expression of contextual fear.

Abstract

Contextual fear conditioning has been shown to activate a set of “fear ensemble” cells in the hippocampal dentate gyrus (DG) whose reactivation is necessary and sufficient for expression of contextual fear. The authors previously demonstrated that extinction learning suppresses reactivation of these fear ensemble cells and activates a competing set of DG cells—the “extinction ensemble.” Here, they tested whether extinction was sufficient to suppress reactivation in other regions and used single nucleus RNA sequencing (snRNA-seq) of cells in the dorsal dentate gyrus to examine how extinction affects the transcriptomic activity of fear ensemble and fear recall-activated cells. The authors’ results confirm the suppressive effects of extinction in the dorsal and ventral dentate gyrus and demonstrate that this same effect extends to fear ensemble cells located in the dorsal CA1. Interestingly, the extinction-induced suppression of fear ensemble activity was not detected in ventral CA1. The authors’ snRNA-seq analysis demonstrates that extinction training markedly changes transcription patterns in fear ensemble cells and that cells activated during recall of fear and recall of extinction have distinct transcriptomic profiles. Together, results indicate that extinction training suppresses a broad portion of the fear ensemble in the hippocampus, and this suppression is accompanied by changes in the transcriptomes of fear ensemble cells and the emergence of a transcriptionally unique extinction ensemble. (Published Abstract Provided)