Excitatory synaptic integration mechanism of three types of granule cells in the dentate gyrus

Granule cells (GCs) are mainly responsible for receiving and integrating information from the entorhinal cortex and transferring it to the hippocampus to accomplish memory-related functions such as pattern separation. Owing to the heterogeneity of GCs, there are also two other subtypes, namely semilunar granule cells (SGCs) and hilar ectopic granule cells (HEGCs). In order to investigate their differences, here we examine the disparities in dendritic integration among the different subtypes of GCs. By utilizing biological experimental data, we developed detailed multi-compartment models for each type of GC. Our findings reveal that under the excitatory synaptic inputs (mediated by AMPA receptors), the dendritic integration of GCs, SGCs and HEGCs are linear, sublinear, and supralinear respectively. Furthermore, we propose that the sublinear integration observed in SGCs may be attributed to a high density of V-type potassium channels (K $_{\text{V}}^{}$ ) distributed in dendrites with smaller volume and higher input resistance; while the supralinear integration seen in HEGCs may be due to a high density of T-type calcium channels (Ca $_{\text{T}}^{}$ ) distributed in dendrites with larger volume and lower input resistance. Additionally, sodium channels, six types of potassium channels (K $_{\text{A}}^{}$ , K $_{\text{M}}^{}$ , sK $_{\text{DR}}^{}$ , fK $_{\text{DR}}^{}$ , BK, SK), and two types of calcium channels (Ca $_{\text{N}}^{}$ , Ca $_{\text{L}}^{}$ ) have minimal influence on their respective integration modes. We also found different integration modes exhibit varied somatic firing rates when subjected to different spatial synaptic activation sets, the HEGCs with the supralinear integration demonstrate higher somatic firing rates than the SGCs with the sublinear integration. These results provide theoretical insights into understanding the distinct roles played by these three subtypes of granule cells in memory-related functions within the dentate gyrus.

The online version contains supplementary material available at 10.1007/s11571-025-10226-0.