Integrating adult neurogenesis and human brain organoid models to advance epilepsy and associated behavioral research

Abstract

Epilepsy is a chronic neurological disorder characterized by recurring, unprovoked seizures, asymmetrical electroencephalogram patterns, and other pathological abnormalities. The hippocampus plays a pivotal role in learning, memory consolidation, attentional control, and pattern separation. Impairment of hippocampal network circuitry can induce long-term cognitive and memory dysfunction. In this review, we discuss how aberrant adult neurogenesis and plasticity collectively alter the network balance for information processing within the hippocampal neural network. Subsequently, we explore the potential of human brain organoids integrated into microelectrode array technology as an electrophysiological tool. We also discuss the utilization of a closed-loop platform that connects the brain organoid to a mobile robot in a virtual environment. While in vivo models provide valuable insights into some aspects of epileptogenesis, such as the impact of adult neurogenesis on hippocampal function, brain organoids are indispensable for comprehensively studying epileptogenesis involving genetic mutations that underlie human epilepsy. More importantly, a combinational approach using brain organoids on MEA paves the way for studying impaired plasticity and abnormal information processing within epileptic neural networks. This innovative in vitro approach may provide a new pathway for investigating the behavioral outcomes of aberrant neural networks when integrated with a mobile robot, closing the loop between the neural network in brain organoids and the mobile robot. In this review, we aim to discuss the use of each model to study the behavioral changes in epilepsy and highlight the benefits of both in vivo and in vitro models for understanding the behavioral aspects of epilepsy.