Scharfman Helen E
Department of Child and Adolescent Psychology, Neuroscience & Physiology, and Psychiatry and the Neuroscience Institute, New York University Grossman School of Medicine, New York University Langone Health, New York, New York, USA.
Center for Dementia Research, The Nathan S. Kline Institute of Psychiatric Research, Orangeburg, New York, USA.
Hippocampus. 2025 Jan;35(1):e23677. doi: 10.1002/hipo.23677.
For many years, the hilus of the dentate gyrus (DG) was a mystery because anatomical data suggested a bewildering array of cells without clear organization. Moreover, some of the anatomical information led to more questions than answers. For example, it had been identified that one of the major cell types in the hilus, the mossy cell, innervates granule cells (GCs). However, mossy cells also targeted local GABAergic neurons. Furthermore, it was not yet clear if mossy cells were glutamatergic or GABAergic. This led to many debates about the role of mossy cells. However, it was clear that hilar neurons, including mossy cells, were likely to have very important functions because they provided strong input to GCs. Hilar neurons also attracted attention in epilepsy because pathological studies showed that hilar neurons were often lost, but GCs remained. Vulnerability of hilar neurons also occurred after traumatic brain injury and ischemia. These observations fueled an interest to understand hilar neurons and protect them, an interest that continues to this day. This article provides a historical and personal perspective into the ways that I sought to contribute to resolving some of the debates and moving the field forward. Despite several technical challenges the outcomes of the studies have been worth the effort with some surprising findings along the way. Given the growing interest in the hilus, and the advent of multiple techniques to selectively manipulate hilar neurons, there is a great opportunity for future research.
多年来，齿状回（DG）的门区一直是个谜，因为解剖学数据显示这里细胞种类繁多却缺乏清晰的组织架构。此外，一些解剖学信息带来的问题比答案还多。例如，已经确定门区的主要细胞类型之一——苔藓细胞，会支配颗粒细胞（GCs）。然而，苔藓细胞也靶向局部的γ-氨基丁酸能神经元。此外，苔藓细胞是谷氨酸能还是γ-氨基丁酸能尚不清楚。这引发了许多关于苔藓细胞作用的争论。然而，很明显包括苔藓细胞在内的门区神经元可能具有非常重要的功能，因为它们为颗粒细胞提供了强大的输入。门区神经元在癫痫中也引起了关注，因为病理学研究表明门区神经元常常缺失，但颗粒细胞却保留了下来。脑外伤和缺血后也会出现门区神经元的易损性。这些观察结果激发了人们了解门区神经元并保护它们的兴趣，这种兴趣一直持续到今天。本文提供了一个历史的和个人的视角，讲述了我为解决一些争论并推动该领域发展所做的努力。尽管面临一些技术挑战，但研究结果还是值得付出努力的，过程中还有一些惊人的发现。鉴于对门区的兴趣日益浓厚，以及多种选择性操纵门区神经元技术的出现，未来的研究有很大的机会。
