Epigenetic and transcriptional basis of memory engram plasticity

Project Information

MemoPlasticGenomics

Grant agreement ID: 101039734

DOI

10.3030/101039734

EC signature date 16 June 2022

Start date 1 August 2022

End date 31 July 2027

Funded under

• European Research Council (ERC)

Total cost

€ 1 499 948,00

EU contribution

€ 1 499 948,00

Coordinated by

AARHUS UNIVERSITET
Denmark

Periodic Reporting for period 1 - MemoPlasticGenomics (Epigenetic and transcriptional basis of memory engram plasticity)

Reporting period: 2022-08-01 to 2025-01-31

Summary of the context and overall objectives of the project

This research project focuses on understanding how memories are formed and stored in the brain by studying specific groups of neurons known as memory engram cells. The primary objective is to unravel the molecular and genetic mechanisms that allow these neurons to encode, maintain, and modify memories. The project also involves developing innovative genomic technologies to trace the history of gene activity in neurons, offering insights into how brain cells respond to experiences over time.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Memory Engram Analysis: The team analyzed neurons from different brain regions (amygdala, hippocampus, and prefrontal cortex) involved in memory formation. By isolating these cells and performing advanced sequencing techniques, they identified genes that are specifically activated during learning. These findings provide insights into how different brain areas contribute to memory.

Single-Cell Multiome Analysis: A cutting-edge technique combining single-cell RNA and chromatin analysis was employed to study how different types of neurons respond to learning. This approach helped identify unique genetic programs that are activated in response to specific stimuli. Notably, we developed a novel bioinformatics pipeline of single-cell Multiome data utilizing Fos motif score of enhancer elements, to robustly identify memory engram cells in a post-hoc manner. This leads us to identify genes that are selectively activated by learning experience, but not by baseline activity in the homo cage environment.

Understanding Gene Induction Mechanisms: The researchers explored how various stimuli (like neurotrophins, stress, or neuronal activity) influence memory-related gene activation. They discovered that distinct signaling pathways trigger specific gene responses, contributing to the diversity of memory-encoding cells.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The identification of learning-specific gene programs across brain regions marks a significant advancement in understanding how different parts of the brain coordinate to store memories. This research could lead to targeted therapies for memory-related disorders, including posttraumatic stress disorder and dementia.