Evolution of debate on the human adult hippocampal neurogenesis

Whether the adult human continues to generate new neurons in the hippocampal dentate gyrus has been a matter of enduring scientific interest and contention. While rodent studies benefit from a broad repertoire of in vivo and histological approaches, human investigations have remained constrained by limited tissue access and methodological hurdles. Species differences have further compounded the challenge, leaving human AHN still lacking robust and reliable biomarkers. Recent methodological innovations, particularly in tissue processing and single‑nucleus RNA sequencing, have begun to clarify the picture, yet substantial controversy remains, with the focus evolving from a categorical question of whether AHN occurs in adults to a more refined examination of its extent, functional significance, and association with diseases. Here, we trace the historical trajectory of human AHN research and its associated debates, covering early histological observations, intermediate attempts at in vivo investigation, the intense controversy over whether AHN persists into adulthood, and more recent developments in method optimization and omics applications that have yielded new insights and opportunities. Finally, we outline remaining uncertainties and future perspectives, and propose a framework for the discovery of human AHN markers and the characterization of their functional relevance.