• hippocampus;
  • in vivo;
  • mossy cells;
  • network properties;
  • synaptic plasticity


Granule cells of the hippocampal dentate gyrus receive two powerful excitatory inputs: the perforant path, originating from the entorhinal cortex, and the associational pathway, originating from mossy cells, the principal neurons of the dentate gyrus hilus. We examined the electrophysiological properties of the less well-studied associational pathway and its interaction with the perforant path in the intact mouse hippocampus and then tested homosynaptic, trans-synaptic and associative long-term potentiation of these pathways. The associational pathway was either monosynaptically activated by stimulation within the inner molecular layer or trisynaptically activated after stimulation of the perforant path. Laminar profiles of extracellularly recorded associational pathway field potentials demonstrated a bell-shaped curve with a peak in the inner molecular layer. Tetanization of the perforant path induced not only homosynaptic potentiation of the perforant path (162.4 ± 6.7% at 0.5–1.5 h after tetanus) but also heterosynaptic potentiation of the associational pathway (115.7 ± 4.9%). Direct tetanization of the associational pathway within the inner molecular layer was ineffective in either the septo-temporal (97.2 ± 4.5%) or temporal-septal (104.4 ± 4.6%) direction. In contrast, conjoint tetanization of the associational pathway with the perforant path potentiated the associational pathway responses in both the septo-temporal (123.4 ± 5.8%) and the temporal-septal (124.8 ± 7.3%) directions. Paired-pulse facilitation was attenuated by long-term potentiation in the perforant path and the associational pathway, suggesting pre-synaptic involvement. These results demonstrate that long-term potentiation of the associational pathway and the perforant path is a product of the network properties of the dentate gyrus rather than of each monosynaptic input alone. The architecture of this neural network may be designed for flexible dynamic associations of the afferent perforant path inputs to configure encoded information within hippocampal neuronal ensembles.