Chavan Parimal, Kitamura Takashi, Sakaguchi Masanori
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Neurobiol Learn Mem. 2025 Jul;220:108062. doi: 10.1016/j.nlm.2025.108062. Epub 2025 May 8.
This review provides an integrative overview of the functional roles of adult neurogenesis in the hippocampal dentate gyrus (DG), focusing specifically on its impact on memory processes across the lifespan. A distinguishing feature of this review is its systematic approach, organizing the contributions of adult-born neurons (ABNs) chronologically through the stages of memory-from initial encoding, through sleep-dependent consolidation, retrieval, and finally forgetting. Although the existence and extent of adult neurogenesis in the human DG remain debated, accumulating evidence suggests that ABNs support cognitive functions throughout adulthood. This perspective gains particular importance when considering cognitive decline associated with aging and neurological disorders such as Alzheimer's disease, which are linked to substantial reductions in adult neurogenesis. We compare traditional models of DG function with emerging evidence highlighting both shared and unique contributions of ABNs. For example, the DG is well-established for its role in pattern separation, and as key mediators of this function, ABNs-due to their transiently heightened plasticity and excitability-appear critical for discriminating novel or similar experiences. On the other hand, recent findings underscore the distinct and essential role of ABNs in memory consolidation during REM sleep, suggesting specialized functions of ABNs that are absent in developmentally born granule cells in the DG. Clinically, the potential therapeutic importance of enhancing neurogenesis in memory-related disorders, including post-traumatic stress disorder (PTSD), is emphasized, highlighting promising treatments such as memantine. Lastly, we outline key unresolved questions, advocating for future research aimed at understanding ABN-specific mechanisms. Far from being a mere evolutionary vestige, hippocampal ABNs represent dynamic and essential elements of neural plasticity that are critical for memory formation, adaptation, and resilience across the lifespan.
本综述对成年神经发生在海马齿状回(DG)中的功能作用进行了综合概述,特别关注其对整个生命周期记忆过程的影响。本综述的一个显著特点是其系统的方法,通过记忆的各个阶段——从初始编码、依赖睡眠的巩固、检索,到最终遗忘,按时间顺序组织成年新生神经元(ABN)的贡献。尽管人类DG中成年神经发生的存在和程度仍存在争议,但越来越多的证据表明,ABN在整个成年期都支持认知功能。当考虑与衰老和神经疾病(如阿尔茨海默病)相关的认知衰退时,这一观点尤为重要,这些疾病与成年神经发生的大幅减少有关。我们将DG功能的传统模型与突出ABN共同和独特贡献的新证据进行了比较。例如,DG在模式分离中的作用已得到充分证实,作为这一功能的关键调节因子,ABN由于其短暂增强的可塑性和兴奋性,似乎对区分新的或相似的经历至关重要。另一方面,最近的研究结果强调了ABN在快速眼动睡眠期间记忆巩固中的独特而重要的作用,表明ABN具有DG中发育产生的颗粒细胞所没有的特殊功能。在临床上,强调了增强神经发生在包括创伤后应激障碍(PTSD)在内的记忆相关疾病中的潜在治疗重要性,突出了美金刚等有前景的治疗方法。最后,我们概述了关键的未解决问题,倡导未来开展旨在了解ABN特异性机制的研究。海马ABN远非仅仅是进化遗迹,而是神经可塑性的动态且重要的元素,对整个生命周期的记忆形成、适应和恢复力至关重要。