Longitudinal Excitation and Lamellar Feedforward Inhibition of the Hippocampal CA3 to CA1 Projections

The hippocampus is a longitudinally extended brain structure characterized by its classic trisynaptic circuit, comprising the dentate gyrus (DG), CA3, and CA1 subregions, evident in transverse slices and consistent throughout the hippocampal formation. Traditionally, the hippocampal circuit's intrinsic features have been studied using transverse slices. However, the trisynaptic flow extends beyond the transverse plane; Schaffer collaterals, the excitatory projections from CA3 to CA1, also extend along the longitudinal (septotemporal) axis. Despite the anatomical establishment of Schaffer collaterals' longitudinal projection, its physiological properties remain underexplored. In this study, we recorded the transverse and longitudinal transmission of Schaffer collaterals using photostimulation with channelrhodopsin-2 (ChR2) expression. Our results revealed that optically evoked inhibitory postsynaptic currents (oIPSCs) were significantly smaller in distal CA1 compared to proximal CA1, while optically evoked excitatory postsynaptic currents (oEPSCs) remained consistent along the longitudinal axis. Additionally, CA1 interneurons mediating feedforward inhibition received smaller oEPSCs in distal planes. These findings indicate that Schaffer collaterals transmit excitatory signals more effectively than inhibitory signals along the longitudinal axis of the hippocampus.