Kempermann Gerd
German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Dresden, Germany.
Front Neurosci. 2022 Apr 15;16:852680. doi: 10.3389/fnins.2022.852680. eCollection 2022.
Adult hippocampal neurogenesis is a unique and exceptional process in the mammalian brain that in a lifelong and activity-dependent way generates new excitatory principal neurons. A comprehensive view on their function in greater contexts has now emerged, revealing to which extent the hippocampus (and hence brain and mind) depend on these neurons. Due to a postmitotic period of heightened synaptic plasticity they bias incoming excitation to the dentate gyrus to non-overlapping subnetworks, resulting in pattern separation and the avoidance of catastrophic interference. Temporally, this promotes the flexible integration of novel information into familiar contexts and contributes to episodic memory, which in humans would be critical for autobiographic memory. Together these local effects represent a unique strategy to solve the plasticity-stability dilemma that all learning neuronal networks are facing. Neurogenesis-dependent plasticity also improves memory consolidation. This relates to the surprising involvement of adult neurogenesis in forgetting, which is also hypothesized to be critically relevant for negative plasticity, for example in post-traumatic stress disorder. In addition, adult-born neurons also directly mediate stress-resilience and take part in affective behaviors. Finally, the activity- and experience-dependent plasticity that is contributed by adult neurogenesis is associated with an individualization of the hippocampal circuitry. While a solid and largely consensual understanding of how new neurons contribute to hippocampal function has been reached, an overarching unifying theory that embeds neurogenesis-dependent functionality and effects on connectomics is still missing. More sophisticated multi-electrode electrophysiology, advanced ethologically relevant behavioral tests, and next-generation computational modeling will let us take the next steps.
成年海马体神经发生是哺乳动物大脑中一个独特且特殊的过程,它以终身且依赖活动的方式产生新的兴奋性主神经元。如今,对于它们在更广泛背景下的功能已形成了全面的认识,揭示了海马体(进而大脑和心智)在多大程度上依赖这些神经元。由于有一个突触可塑性增强的有丝分裂后时期,它们将传入齿状回的兴奋偏向不重叠的子网络,从而导致模式分离并避免灾难性干扰。从时间上看,这促进了新信息灵活融入熟悉的情境,并有助于情景记忆,这在人类中对于自传体记忆至关重要。这些局部效应共同代表了一种独特的策略,以解决所有学习神经元网络都面临的可塑性 - 稳定性困境。依赖神经发生的可塑性还能改善记忆巩固。这与成年神经发生在遗忘过程中的惊人参与有关,据推测这对于负性可塑性也至关重要,例如在创伤后应激障碍中。此外,成年新生神经元还直接介导应激恢复力并参与情感行为。最后,成年神经发生所贡献的依赖活动和经验的可塑性与海马体回路的个体化相关。虽然对于新神经元如何促进海马体功能已达成了坚实且在很大程度上一致的理解,但仍缺少一个将依赖神经发生的功能和对连接组学的影响纳入其中的总体统一理论。更复杂的多电极电生理学、与行为学相关的先进行为测试以及下一代计算建模将使我们能够迈出下一步。