Biphasic expression of plasticity genes in the stabilization of hippocampal and neocortical fear memory neuronal ensembles.

• Applicant: Professorin Dr. Ana M. M. Oliveira
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 428561042

Although persistence is a key characteristic of some memories, what determines whether a memory will be transiently or permanently-stored is not understood. A few studies and our own preliminary work show that consolidation of persistent memories is associated with the reactivation of expression of plasticity-related genes at later time points after learning in both hippocampal and neocortical regions. Importantly, transcriptional reactivation is absent after experiences which are only stored for short periods of time. We therefore hypothesize that transcriptional reactivation provides a molecular and cellular reinforcement mechanism necessary for the stabilization of neuronal ensembles underlying long-lasting forms of memory. We will address this hypothesis in a fear-memory paradigm. First, we will determine whether the late transcriptional response occurs selectively within the neuronal ensemble formed at the time of learning, and whether it is necessary for long-term stabilization of memory representations. This will be achieved by combining ensemble-tagging tools and immunohistological analysis. Second, we will identify the cellular correlates of learning experiences triggering memories of different duration. We will characterize functional and structural features of the -tagged- neuronal ensemble(s) associated with short-lasting and long-lasting memory. Our preliminary findings show that learning stimuli inducing short or long forms of memory trigger distinct expression patterns of plasticity-related genes. Therefore, we will test whether expression of these plasticity-related genes determines the different properties of neuronal ensembles associated with short or long-lasting memory. Finally, we will investigate whether impaired memory persistence in aged animals is a result of disrupted stabilization of neuronal ensembles. We hypothesize that transcriptional reactivation of plasticity-related genes is reduced in the hippocampus and neocortex of aged mice. Together, our experiments will help revealing whether and how transcriptional reactivation determines the stability of hippocampal and neocortical ensembles associated with long-lasting memory.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Andreas Draguhn