Ipsilateral associational pathway in the dentate gyrus: an excitatory feedback system that supports N-methyl-D-aspartate-dependent long-term potentiation

Axons from granule cells in the dentate gyrus of the rat hippocampus project to cells in the hilar region, including mossy cells, which project along the longitudinal axis of the hippocampus and synapse in the inner (proximal) one-third of the molecular layer of the dentate gyrus. To study this feedback system, multiple recording electrodes were located along the longitudinal (septo-temporal) axis in the dorsal leaf of the dentate gyrus in urethane-anesthetized rats. Single pulse electrical stimuli delivered to the hilar region evoked negative-going, monosynaptic field potentials that were largest in the inner one-third of the molecular layer (commissural zone). These evoked field potentials (EFPs) were recorded simultaneously at three to five locations. The latency to onset and peak amplitude of the EFP varied linearly with distance from point of stimulation, and EFPs were elicited in both directions along the longitudinal axis. The transmission speed was estimated to be 1.4 m/s. Tetanic stimulation of the hilar region potentiated the EFP slopes (mean = 26%). Potentiation lasted at least 2 hours and was specific to responses from the tetanized stimulating electrode; the responses to other stimulating electrodes in the hilus and the angular bundle of the perforant path changed less than 4%. Combined stimulation of the hilus and the medial perforant path increased the magnitude of recorded field potentials and population spikes, demonstrating that both pathways are excitatory. NMDA antagonist NPC-17742 blocked potentiation of EFP slopes in both the medial perforant path and hilus pathways. The results suggest that the ipsilateral associational system of the dentate gyrus is excitatory and capable of supporting long-lasting NMDA-dependent, synapse-specific plasticity.