Pathway-specific properties of AMPA and NMDA-mediated transmission in CA1 hippocampal pyramidal cells

Abstract

CA1 pyramidal cells receive glutamatergic input from the entorhinal cortex through the perforant path (PP) and from CA3 through Schaffer collaterals (SC). The PP input terminates in the stratum lacunosum moleculare ∼300 μm from the cell body, whereas SC synapses have a more proximal location in the stratum radiatum. We compared the properties of AMPA- and NMDA-mediated transmission at these two inputs. The AMPA-mediated components have linear voltage dependence in both inputs. The reversal potential in the PP is only slightly more positive than in the SC, indicating that distal membrane voltage could be effectively set. The NMDA-mediated responses in the two pathways, however, are very different. The PP exhibits inward rectification, as evidenced by very low outward currents. The rectification persists in the absence of extracellular Mg2+. It cannot be attributed to clamping problems, because large outward AMPA currents can be observed even when conditions are modified to have the AMPA currents kinetically match the NMDA currents. Thus, it appears that the PP NMDA channels have novel properties. A second difference between the PP and SC pathways is that the PP has a larger NMDA/AMPA charge ratio. This difference could be observed under many conditions, including block of all voltage-dependent conductances and elimination of the negative resistance of NMDA channels by removing extracellular Mg2+. The difference in ratio thus cannot be attributed to regenerative currents. The higher NMDA component of the distal PP synapses could help to make these synapses more powerful under depolarizing conditions.