Regulation of dentate gyrus pattern separation by hilus ectopic granule cells

The dentate gyrus (DG) in hippocampus is reported to perform pattern separation, converting similar inputs into different outputs and thus avoiding memory interference. Previous studies have found that human and mice with epilepsy have significant pattern separation defects and a portion of adult-born granule cells (abGCs) migrate abnormally into the hilus, forming hilus ectopic granule cells (HEGCs). For the lack of relevant pathophysiological experiments, how HEGCs affect pattern separation remains unclear. Therefore, in this paper, we will construct the DG neuronal circuit and focus on discussing effects of HEGCs on pattern separation numerically. The obtained results showed that HEGCs impaired pattern separation efficiency since the sparse firing of granule cells (GCs) was destroyed. We provided new insights into the underlining mechanisms of HEGCs impairing pattern separation through analyzing two excitatory circuits: GC-HEGC-GC and GC-Mossy cell (MC)-GC, both of which involve the participation of HEGCs within the DG. It is revealed that the recurrent excitatory circuit GC-HEGC-GC formed by HEGCs mossy fiber sprouting significantly enhanced GCs activity, consequently disrupted pattern separation. However, another excitatory circuit had negligible effects on pattern separation due to the direct and indirect influences of MCs on GCs, which in turn led to the GCs sparse firing. Thus, HEGCs impair DG pattern separation mainly through the GC-HEGC-GC circuit and therefore ablating HEGCs may be one of the effective ways to improve pattern separation in patients with epilepsy.