Interaction of inputs in hippocampal granule cells with inhibitory connections

Abstract

The hippocampus integrates non-spatial information (such as objects and odors) and spatial information (places). The dentate gyrus is the gate for inputinformation to the hippocampus. Non-spatial information and spatial information are independently transported from the entorhinal cortices to separated sites, the distal dendrite and the medial dendrite of granule cells (GCs) within the molecular layer in the dentate gyrus, respectively. To investigate the interaction of those two inputs, response characteristics of distal and medial dendrites of GCs were independently measured at 0.1-40Hz of input frequency in a rat hippocampal slice where inhibitory input was blocked by application of picrotoxin, GABAergic receptors antagonist. From those experimental data, a multi-compartment GC model with dynamic synapses was developed using NEURON simulator. Model simulations were performed using the model which reproduced the response characteristics of the dendrites of a GC. As the results, when the random and theta burst inputs were simultaneously applied to the respective dendrites, the pattern discrimination for theta burst input to medial dendrites that caused slight GC activation was enhanced in the presence of random input to distal dendrites. These results suggest that the temporal pattern discrimination of spatial information is originally involved in a synaptic characteristic in GCs and is enhanced by nonspatial information input to distal dendrites. Furthermore, to investigate a role of inhibitory neurons for the interaction between medial and distal inputs in the dentate gyrus, response characteristics were also physiologically measured in the presence of inhibitory inputs, without picrotoxin. In addition, model simulation was also performed. It was found that the local inhibitory network played to maintain magnitudes of EPSP for successive inputs to distal dendrite at high-frequency (25-40Hz). The result suggests that inhibitory inputs may support the enhancement of input information to medial dendrites by sustaining responses for input sequence to distal dendrites.