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

Abstract

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.

Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia

“…That is especially likely in the case of DGh cells, all of which were found to be intensely immunoreactive for dysbindin-1. DGh cells provide the only substantial input to DGiml (49), which is known to be glutamatergic (62)(63)(64). That would explain the significant correlation between the dysbindin-1 reduction in DGh cells and that in DGiml in our schizophrenia cases.…”

“…DGh cells regulate HF information flow because (a) they have a lower firing threshold for entorhinal input than DGg cells (66,67), (b) they receive input from DGg cells (49), and (c) they give rise to a recurrent, glutamatergic projection that ends on proximal dendrites of DGg cells over long rostrocaudal segments of the DG (62)(63)(64). Via that recurrent projection, DGh cells can prime or recruit large numbers of granule cells to respond to entorhinal input.…”

Pulse labeling and long-term tracing of newborn neurons in the adult subgranular zone

“…Mossy cell input mediated critical regulation of granule excitability by activities from distant granule cells of ipsilateral hippocampus [13,16]. This connection was also important for the maintenance of NMDA-dependent long-term potentiation [14]. Based on our transgenic technique to dissect MML and IML, we specifically analyzed spine differentiation of IML.…”

“…The dendritic field of granule neuron can be divided into three sub-layers [13]. Spine structure in the inner molecular layer (IML) has long been considered mainly as postsynaptic partner of mossy cells, and this connection is important for modulation of granule cell excitability and plasticity [13][14][15][16]. Recent work found a semilunar granule cells (SGC)-relayed pathway, which recruit mossy cells to refine directly and indirectly the firing of distinct granule cell populations [17].…”

Translamellar Disinhibition in the Rat Hippocampal Dentate Gyrus after Seizure-Induced Degeneration of Vulnerable Hilar Neurons

“…Relatively weak longitudinal excitation has been reported (Bekenstein and Lothman, 1991;Hetherington et al, 1994), but the use of electrical stimulation in these studies makes it difficult to identify the intrinsic pathways or fibers of passage mediating responses recorded within the same stimulated structure. These problems of interpretation led us to use the BMI Figure 6.…”