Epigenetic and transcriptional basis of memory engram plasticity

Información del proyecto

MemoPlasticGenomics

Identificador del acuerdo de subvención: 101039734

DOI

10.3030/101039734

Fecha de la firma de la CE 16 Junio 2022

Fecha de inicio 1 Agosto 2022

Fecha de finalización 31 Julio 2027

Financiado con arreglo a

• European Research Council (ERC)

Coste total

€ 1 499 948,00

Aportación de la UE

€ 1 499 948,00

Coordinado por

AARHUS UNIVERSITET
Denmark

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

Período documentado: 2022-08-01 hasta 2025-01-31

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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.