Modulation of excitability in CA1 pyramidal neurons via the interplay of entorhinal cortex and CA3 inputs

Hippocampal CA1 pyramidal neurons receive extrahippocampal and intrahippocampal inputs. The Schaffer collateral (SC) pathway, projecting to the stratum radiatum of the CA1 field, serves as the primary excitatory input to CA1 cells. The temporoammonic pathway (TA), converging at stratum lacunosum moleculare (SLM), appears to be inhibitory. The relative temporal occurrence of the stimuli conveyed by the two pathways seems to modulate the excitability of CA1 pyramidal neurons. Specifically, the excitatory effect of SC inputs is greatly attenuated when preceded by TA stimulation within a specific time window. This phenomenon is referred to as the spike-blocking effect. Dvorak-Carbone and Schuman found that spike-blocking efficacy temporally coincide with the GABAb signalling pathway, while spike blocking was almost abolished in the presence of GABAb antagonist. In this work, we study the contribution of the GABAb receptor on the aforementioned phenomenon using a refined version of a previously published multicompartmental model of a CA1 pyramidal cell. We also investigate to what extend spike blocking is affected by the spatial arrangement of coincident synaptic inputs in the dendrites of the model neuron. We find that in addition to a temporal regulation, the arrangement of synaptic contacts provides a location-dependent modulation of excitability by the EC input. When synapses are scattered throughout the layered-model cell spike blocking is enhanced whereas spike blocking is reduced with clustered synaptic arrangement. We conclude that spike blocking may act as a mechanism for discriminating weak from strong synaptic inputs.