Input-output relations in the entorhinal cortex-dentate-hippocampal system: evidence for a non-linear transfer of signals.

In the current study we analyzed the input-output relations in the entorhinal-dentate-hippocampal system, a major network involved in long-term memory. In anesthetized guinea pigs, the system was driven by activation of perforant path neurons in the entorhinal cortex (ENT), via presubicular fibers directly stimulated in the dorsal psalterium. Perforant path neuron discharge activated in parallel the dentate gyrus (DG) and hippocampal field CA2. Whereas the output from the DG activated hippocampal field CA3, the output from the sole field CA2 was sufficient for activation of field CA1. Signals from field CA3 operated in concert with CA2, likely contributing to discharge field CA1. These findings indicate the existence of two in parallel disynaptic systems: an ENT-CA2-CA1 and an ENT-DG-CA3 system. The convergence of the latter with the former gives origin the classical trisynaptic circuit, the ENT-DG-CA3-CA1 system. The input-output relations between the population excitatory postsynaptic potentials (pEPSP) evoked in the DG, CA3, CA2 and CA1 and the population spike (PS) evoked in the structure upstream (the input) were described by smooth sigmoid curves. In contrast, the input-output relations of the PS versus the pEPSP within each structure were described by steep sigmoid curves. The net input-output functions of the DG (ENT-DG system), field CA2 (ENT-CA2 system), field CA3 (ENT-DG-CA3 system) and field CA1 (ENT-CA2-CA1&ENT-DG-CA3-CA1 system) were described by sigmoid curves. While the DG and field CA2 exhibited steep sigmoids, fields CA3 and CA1 had less steep sigmoid functions. The present study demonstrates that all structures downstream to the ENT operate according to sigmoid input-output functions, characterized by specific parameters. These different behaviors may contribute to different memory processes. We additionally demonstrate that field CA1 can be activated by field CA2, independently from field CA3. This functional dissociation between CA3 and CA1 may subserve specific roles of each field in memory encoding/retrieval.