Population dynamics in the medial entorhinal cortex of freely flying Egyptian fruit bats - PROJECT SUMMARY / ABSTRACT The internal representation of space in the mammalian brain is crucial for supporting an animal's ability to navigate complex environments. Grid cells in the medial entorhinal cortex (MEC) are believed to provide a reliable and scalable representation of an animal's position through periodic firing fields arranged in a hexagonal pattern during 2D navigation. Recent experimental findings strongly support continuous attractor network (CAN) models that posit that grid cell activity is constrained to a 2D toroidal manifold which, when anchored to behavior, gives rise to structured firing patterns. However, it remains unresolved how grid cells subserve complex spatial behavior such as 3D navigation, and whether CAN models generalize across species with distinct navigational demands. Prior studies investigating grid cells in flying bats suggested that grid cell spatial responses lacked global structure, contrasting sharply with structured grid cell responses found during 2D navigation in both bats and rodents, However, these studies focused on unstructured navigation driven by human intervention, and were limited to single cell analysis of small neural populations. Spatial representations in bats are known to be modulated by non-positional aspects of behavior as well as the presence of human experimenters. Thus, how grid cells represent the bat’s natural, self-selected flight patterns is not well understood. Furthermore, MEC is intricately connected with the hippocampus, which has been shown to reflect the animal’s action plans. However, whether action plans emerge in MEC during ethological goal-directed navigation remains unexplored. By leveraging the ethological advantages of bats and breakthroughs in wireless Neuropixels recording techniques, this proposal aims to examine how grid cells underlie bats' natural, self-selected flight paths during 3D navigation and connect these findings to existing grid cell models. In Aim 1, I will characterize grid cell spatial responses and population dynamics during 3D navigation to test the hypothesis that grid cells exhibit periodic spatial responses along bats’ natural flight paths and whether grid cell population activity is constrained to a toroidal manifold. In Aim 2, I will investigate non- spatial representations to test the hypothesis that MEC reflects navigational action plans during goal-directed 3D navigation. The proposed work could uncover fundamental mechanisms that are conserved across species and may shed light on how MEC supports spatial memory functions, providing vital insights that could help advance therapeutic approaches for neurological disorders such as Alzheimer's. The proposed fellowship training plan provides a comprehensive training strategy to develop the necessary expertise to carry out this research project in the Yartsev Lab, one of the world’s leading bat neuroscience labs.
