Spine Imaging of Grid cells to Uncover the Roles of their Dendritic Inputs

Ziel

The medial entorhinal cortex (MEC) is a key structure for spatial navigation and memory. One of the most studied cell types in this brain region is the grid cells, which are activated in a spatial hexagonal pattern, forming the coordinate system of the cognitive map to support path integration and navigation. Despite their importance, we still lack a mechanistic understanding of how their synaptic inputs influence and generate their activity. This project will develop subcellular-resolution MINI2P microscopy combined with calcium imaging to uncover the synaptic mechanisms underlying grid cell function in freely moving animals. Theoretical work suggests that grid cells receive input from other grid cells and spatially tuned non-grid cells as head-direction and border cells yet direct experimental evidence of these connections is still missing. Therefore, using the developed MINI2P, I will examine whether grid cells receive excitatory input from phase-matched or different phase grid cells, furthermore I will identify and classify inputs from other spatially tuned populations revealing how heterogeneous spatial signals converge and generate grid coding. Finally, I will quantify the spatial distribution, clustering, and synchrony of excitatory inputs along dendritic branches, uncovering the microcircuit rules of dendritic integration that drive grid periodicity. Together, these aims will bridge the gap between synaptic-scale mechanisms and network-level models of spatial coding. The project introduces a novel methodology for studying dendritic integration in behaving animals and will generate transformative insights into how the MEC constructs spatial representations.