Feedforward inhibition (FFI) between the dentate gyrus (DG) and CA3 sparsifies and
shapes memory- and spatial navigation-related activities. However, our understanding
of this prototypical FFI circuit lacks essential details, as the wiring of FFI is
not yet mapped between individual DG granule cells (GCs) and CA3 pyramidal cells (PCs).
Importantly, theoretically opposite network contributions are possible depending on
whether the directly excited PCs are differently inhibited than the non-excited PCs.
Therefore, to better understand FFI wiring schemes, we compared the prevalence of
disynaptic inhibitory postsynaptic events (diIPSCs) between pairs of individually
recorded GC axons or somas and PCs, some of which were connected by monosynaptic excitation,
while others were not. If FFI wiring is specific, diIPSCs are expected only in connected
PCs; whereas diIPSCs should not be present in these PCs if FFI is laterally wired
from individual GCs. However, we found single GC-elicited diIPSCs with similar probabilities
irrespective of the presence of monosynaptic excitation. This observation suggests
that the wiring of FFI between individual GCs and PCs is independent of the direct
excitation. Therefore, the randomly distributed FFI contributes to the hippocampal
signal sparsification by setting the general excitability of the CA3 depending on
the overall activity of GCs.
