Synaptic interactions between stellate cells and parvalbumin interneurons in layer 2 of the medial entorhinal cortex are organized at the scale of grid cell clusters

Interactions between excitatory and inhibitory neurons are critical to computations in cortical circuits but their organization is difficult to assess with standard electrophysiological approaches. Within the medial entorhinal cortex, representation of location by grid and other spatial cells involves circuits in layer 2 in which excitatory stellate cells interact with each other via inhibitory parvalbumin expressing interneurons. Whether this connectivity is structured to support local circuit computations is unclear. Here, we introduce strategies to address the functional organization of excitatory-inhibitory interactions using crossed Cre- and Flp-driver lines to direct targeted presynaptic optogenetic activation and postsynaptic cell identification. We then use simultaneous patch-clamp recordings from postsynaptic neurons to assess their shared input from optically activated presynaptic populations. We find that extensive axonal projections support dense but incomplete connectivity between stellate cells and parvalbumin interneurons. Analysis of the spatial organization of synaptic interactions is consistent with local modules defined by excitatory-inhibitory connectivity. We suggest that dense, but specific, direct excitatory-inhibitory synaptic interactions may operate at the scale of grid cell clusters, while indirect interactions may coordinate activity at the scale of grid cell modules.