REMGRAM is a neuroscience research project that investigates how the brain decides which parts of an experience are stored as long-term memories and which are progressively forgotten. Understanding these mechanisms is essential because memory dysfunction is a central feature of neurological and psychiatric disorders such as Alzheimer’s disease and post-traumatic stress disorder (PTSD), which affect millions of people in Europe.
When people remember an event after a long period of time, they usually retain only its most meaningful or emotional aspects, while many details disappear. Although scientists already know a great deal about how memories are initially formed, it is still unclear why some components of an experience survive over time while others fade away. REMGRAM aims to answer this question by studying how different groups of neurons contribute to the formation of recent and remote memories.
The project focuses on “engrams”, which are groups of neurons activated during an experience and believed to physically store memories in the brain. Previous research has shown that memories are initially dependent on the hippocampus, a brain region involved in episodic memory, and later become more dependent on cortical regions associated with long-term and generalized memory storage. However, the biological mechanisms that determine which specific aspects of an experience are transferred into long-lasting cortical memories remain unknown.
To address this challenge, REMGRAM uses a cutting-edge optogenetic technology called FLiCRE. This method allows researchers to label and manipulate neurons that are active during very precise moments of an experience, with a temporal resolution of only a few seconds. Unlike previous technologies, which could only identify neurons active over long periods of time, FLiCRE makes it possible to distinguish between different neuronal populations involved in separate components of the same event.
Using mouse models of contextual fear memory, REMGRAM will identify neurons activated during specific behavioral phases (exploration, shock-delivery, freezing behavior and others). The project will investigate whether these distinct neuronal populations contribute differently to the formation of recent memories and long-term remote memories.
The research combines several advanced neuroscience techniques, including optogenetics, calcium imaging, behavioral analysis, histology, and computational neuroscience. Real-time behavioral tracking systems will be used to selectively label neurons during specific actions performed by the animals. Subsequently, neuronal activity will be monitored and manipulated to determine how individual memory components are stored, stabilized, generalized, or forgotten over time.
Beyond its scientific importance, REMGRAM has significant societal relevance. Better understanding of how memories are selected and stabilized in the brain could support the future development of therapies aimed at preventing memory loss or reducing maladaptive memory persistence in neurological and psychiatric disorders. The findings may contribute to future non-invasive strategies to improve cognitive health and quality of life in ageing populations and patients affected by memory-related diseases.
The project also contributes to methodological innovation in neuroscience by demonstrating the use of highly precise neuronal labeling technologies to study memory processes. These approaches could later be applied to other areas of behavioral and brain research.
REMGRAM strongly supports open science practices. Research results, protocols, and publications will be made openly accessible through open-access journals, preprint servers, and public repositories. The project also includes communication and outreach activities designed to increase public awareness of neuroscience research, brain health, and the importance of animal models in biomedical science.
Overall, REMGRAM aims to generate new knowledge about the biological foundations of memory persistence and forgetting, while also developing innovative tools and approaches that may benefit the broader neuroscience community and future translational research.
