Dissecting the role of subiculum in epilepsy: Research update and translational potential

The subiculum serves as the strategic core output of the hippocampus, through which neural activity exits the hippocampal proper and targets the entorhinal cortex and other more distant subcortical and cortical areas. The past decade has witnessed a growing interest in the subiculum, owing to discoveries revealing its critical role in regulating many physiological and pathophysiological processes. Notably, accumulating evidence from both clinical and experimental studies suggests that the subiculum plays a vital role in seizure initiation and propagation, in epilepsy. In this review, we briefly describe the structure and connectivity of the subiculum and then summarize the molecular and cellular mechanisms in the subiculum underlying the epileptic brain, in both epilepsy patients and animal models. Next, we review some translational approaches targeting the malfunctioned subiculum to treat epilepsy. Finally, we pose open questions for future research in the subiculum and their clinical translation challenges.