Impact of the entorhinal feed-forward connection to the CA3 on hippocampal coding

Each sub-region of the hippocampus plays a critical computational role in the formation of episodic learning and memory, but studies have yet to show and interpret the individual spiking dynamics of each region and how that information is passed between each subregion. This is in part due to the difficulty in accessing individual communicating axons. Here, we created a novel microfluidic device that facilitates network growth of four separated hippocampal subregions over a micro-electrode array. This device enabled monitoring single axons over two electrodes so direction of spike propagation in interregional communication could be ascertained. In this in vitro hippocampal study, we compared spiking dynamics across two novel four-compartment device architectures: one with four sets of axon tunnels between subregions that excluded the perforant pathway from EC-CA3, and one with five sets of axon tunnels that included the EC-CA3 connection. We found 30-90% faster feed-forward firing rates (shorter interspike intervals) in axons in the five-tunnel model with 35-75% slower bursting dynamics (longer interburst intervals) compared to the four-tunnel model. The CA3-CA1 and CA1-EC axons had more spikes in bursts in the five-tunnel architecture than the four-tunnel counterpart suggesting more structured information transfer. Feedback firing rates were similar between configurations. The faster feed-forward inter-regional spiking in the more natural five-tunnel than the four-tunnel configuration suggests tighter control of spiking and possibly more precise communication between subregions.