How do spatial maps emerge in the medial entorhinal cortex during learning and how does this information relate to spatial representations in the downstream mouse hippocampus?

• Applicant: Thibault Cholvin, Ph.D.
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537575602

The medial entorhinal cortex (MEC) plays a key role in the processing, storage and recall of environmental information by providing essential information on space and context to its downstream hippocampal areas, the dentate gyrus and CA1-3. However, whether contextual and spatial information is immediately encoded and stabilized from the first exposure to a novel environment onwards or whether this contextual representation improves over time through a learning process spanning across several days (as observed for the dentate gyrus; Cholvin & Bartos, 2022) remains to be demonstrated. To address this fundamental question, we aim to apply our established in vivo two-photon calcium imaging of MEC boutons (axonal projections) in the three hippocampal areas, the dentate gyrus, CA3 and CA1, in head-fixed mice navigating through virtual environments. By imaging large MEC-to-hippocampus bouton populations, we recently revealed that these projections show spatially tuned activity patterns, but also that MEC inputs drastically change their preferred spatial field locations between different virtual environments, indicating that contextual discrimination is already present at the level of the MEC (Cholvin et al., 2021). Spatial tuning characteristics of MEC inputs across time and learning have so far, however, not been examined. Here we therefore aim to (1) image MEC inputs in the three hippocampal areas over 5 consecutive days by exposing mice to a novel virtual reality in alternation to an already known familiar one and determine the characteristics of spatial MEC representations across learning; (2) examine the relationship between MEC inputs and spatial representation in the hippocampus across days of learning in the novel environment; (3) determine the influence of MEC inputs on spatial discrimination in the hippocampus by modulating their activity using established chemogenetic tools; (4) apply decoding analysis on the activity of MEC inputs and principal cells in the hippocampus to examine whether and how information about location and context emerges with time and experience in the MEC and hippocampus. In summary, our main goal is to examine how MEC inputs activity carrying information about space and context evolves over time (i.e. with learning), and how this information is refined into a spatial map in the hippocampus.

• DFG Programme: Research Grants