The Ins and Outs of the dentate gyrus for memory trace formation and behavior

• Applicant: Professorin Dr. Marlene Bartos
• Subject Area: Experimental and Theoretical Network Neuroscience
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 561281570

How spatial and contextual information is processed in the brain to enable individual organisms to adapt to their continuously changing environment has been largely studied in the hippocampus, and particularly in CA1, the hippocampal output area broadcasting contextual information to neocortical areas for long-term storage. However, little progress has been made on ‘how novel information from the external world is converted into discrete memory traces in the dentate gyrus (DG), the input gate of the hippocampus, and the role of this information in shaping population activity in down-stream hippocampal areas and context-related behavioral control.’ Here, we aim to address this fundamental question by applying our recently established high-resolution 2-Photon (2P) calcium imaging technique to record and manipulate neuronal DG activity at cellular and subcellular resolution in head-fixed mice performing memory-guided behavior in virtual realities. First, we aim to visualize input activity patterns of the three main afferent input streams to the DG, the lateral & medial entorhinal cortex (LEC & MEC, respectively) providing information on the ‘what’ and ‘where’ of the environment, as well as the hilus, containing mossy cells (MCs) that provide information on spatial ‘novelty’. Second, we aim to determine how the input activity relates to the activity of granule cells (GCs), the main principal cell output of the DG, which forward the processed environ-mental information to downstream hippocampal regions. Third, by using holographic manipulation of GC ensemble activity representing a given environment, we will test the hypothesis that the DG output is important for the recall of experienced contexts, as reflected by the animals’ behavior. By probing the relationship between the afferent synaptic inputs (Ins) and the GC outputs (Outs), we will advance towards a better understanding of the emergence of novel memory traces in the DG, their relevance in shaping animal behavior, and, thus, shed light on the functional role of one of the least understood hippocampal areas, which has been proposed to be involved in sever-al mnemonic functions.

• DFG Programme: Reinhart Koselleck Projects