Project Details
Projekt
Epigenetic control of long-lasting cortical memory representations
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Cognitive, Systems and Behavioural Neurobiology
Cognitive, Systems and Behavioural Neurobiology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 450801794
Memories are the record of our experiences and are essential in shaping future behaviors. Significant progress has been made in the understanding of how memories are formed, however, how some memories transform into persistent memories (remote memory) is poorly understood. Recently it has been shown that memories are stored within the neuronal population – or neuronal ensemble – selected at the time of learning and reactivated when the memory is retrieved. However, the molecular and cellular processes that underlie the stabilization of cortical neuronal ensembles and ensure that the sparse subset of neurons activated during learning is recruited to successfully recreate aspects of a learning event that occurred days and weeks before are unknown. Here, we propose that long-term storage of memory in cortical networks is supported by epigenetic mechanisms. DNA methylation regulation in the medial prefrontal cortex (mPFC) has been associated with remote memory and we recently provided a link between DNA methylation and neuronal ensemble stability. We hypothesize that DNA methylation guides plasticity changes within cortical neuronal ensembles that ensure its reactivation during remote memory recall. To test this, we will probe the DNA methylation and transcriptomic landscapes of mPFC ensembles supporting remote fear memory. Furthermore, we will establish causality between cortical DNA methylation mechanisms, the duration of memory and the stability of associated neuronal ensembles. This will be achieved through a combination of loss- and gain-of-function experiments. Lastly, we will investigate whether DNA methylation mechanisms within cortical neuronal ensembles guide neuronal structural changes that support remote memory storage. The proposed research program promises to start uncovering the unexplored cellular and molecular basis of memory maintenance.
DFG Programme
Research Grants
