Septohippocampal and commissural pathways antagonistically control inhibitory interneurons in the dentate gyrus

Available evidence suggests that a portion of the septohippocampal pathway may form inhibitory synapses on inhibitory interneurons in the dentate gyrus. In contrast, a portion of the commissural input from the contralateral hilus may form excitatory synapses on inhibitory interneurons. To ascertain whether these pathways synapse onto a common population of interneurons, a series of pulses were applied and their effects on perforant path evoked, granule cell population spikes were measured. The population spike was markedly reduced when the perforant path pulse was preceded by a pulse to the contralateral hilus. This inhibition was markedly reduced, however, when a medial septal pulse was applied either prior to, or within 3 ms after the commissural pulse. The disinhibition was critically dependent on the temporal relationship between the medial septal and commissural pulse, and not on the medial septal-perforant path relationship. This finding suggests that the septohippocampal pathway inhibits the interneurons through which the commissural pathway is able to inhibit granule cells.