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. Comparing the percentage of spikes in bursts between
array designs, the five-tunnel architecture showed that the CA3-CA1 and
CA1-EC axons had more spikes in bursts 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 configuration than
with four-tunnel suggests tighter control of spiking and possibly more
precise communication between subregions.