The hippocampus is a brain structure which contains the neural networks for learning and memory, and the dentate gyrus is a gateway for the hippocampal networks. Granule cells are primary neurons in the dentate gyrus, and receive excitatory inputs mainly from the entorhinal cortex via perforant-path.
Serotonin (5-HT) is known to modulate the activity of GABAergic interneurons in the dentate gyrus, which indirectly affects the excitatory inputs from the perforant-path. A possible direct modulation of the excitatory synapses by 5-HT is, however, not well examined.
In the present study, we examined the actions of 5-HT on the excitatory synapses in granule cells under the condition in which GABAergic inputs were blocked by picrotoxin. 5-HT (1 μM) decreased the input resistance (IR) of granule cells around 50 % and shortened the decay of EPSPs evoked by stimulation of the perforant-path. Computer simulation showed that such reduction of IR decreases EPSPs around 30 % at most. We, however, observed more than 50 % reduction of EPSPs evoked by the lateral perforant path (LPP) in some preparations. Moreover, the synaptic transmission failure and the paired-pulse ratio (PPR) were often increased by 5-HT, suggesting that 5-HT reduces the release probability of the LPP synapse. These effects were suppressed by a 5-HT_1A receptor antagonist, WAY100635. On the other hand, 5-HT did not reduce the amplitude of EPSPs evoked by the medial perforant path (MPP) and the PPR was rather decreased, suggesting that 5-HT may enhance the release probability of the MPP synapse. These results suggest that 5-HT induces pathway-specific modulation of excitatory inputs to the dentate granule cells.