Department of Biomedicine, University of Basel, Pestalozzistr. 20, CH-4056 Basel, Switzerland.
Department of Biomedicine, University of Basel, Pestalozzistr. 20, CH-4056 Basel, Switzerland.
Behav Brain Res. 2019 Oct 17;372:112036. doi: 10.1016/j.bbr.2019.112036. Epub 2019 Jun 13.
In the adult hippocampus new neurons are continuously generated throughout life and integrate into the existing network via the formation of thousands of new synapses. Adult-born granule cells are known to improve learning and memory at about 3-6 weeks post mitosis by enhancing the brains ability to discriminate similar memory items. However, the underlying mechanisms are still controversial. Here we review the distinct functional properties of the newborn young neurons, including enhanced excitability, reduced GABAergic inhibition, NMDA-receptor dependent electrogenesis and enhanced synaptic plasticity. Although these cellular properties provide a competitive advantage for synapse formation, they do not generate 'hyperactivity' of young neurons. By contrast, in vivo evidence from immediate early gene expression and calcium imaging indicates that young neurons show sparse activity during learning. Similarly, in vitro data show a low number of high-impact synapses, leading to activation young cells by distinct subsets of afferent fibers with minimal overlap. Overall, the enhanced excitability of young cells does not generate hyperactivity but rather counterbalance the low number of excitatory input synapses. Finally, sparse coding in young neurons has been shown to be crucial for neurogenesis-dependent improvement of learning behavior. Taken together, converging evidence from cell physiology and behavioral studies suggests a mechanism that can explain the beneficial effects of adult neurogenesis on brain function.
在成年人的海马体中,新的神经元会在整个生命过程中不断产生,并通过形成数千个新的突触整合到现有的网络中。已知成年产生的颗粒细胞可以通过增强大脑区分相似记忆项目的能力,在有丝分裂后 3-6 周左右改善学习和记忆。然而,其潜在机制仍存在争议。在这里,我们回顾了新生神经元的独特功能特性,包括增强的兴奋性、减少的 GABA 能抑制、NMDA 受体依赖性电生成和增强的突触可塑性。尽管这些细胞特性为形成突触提供了竞争优势,但它们不会产生新生神经元的“过度活跃”。相比之下,即时早期基因表达和钙成像的体内证据表明,新生神经元在学习过程中表现出稀疏的活动。同样,体外数据显示,高影响突触的数量较少,导致传入纤维的不同子集以最小的重叠激活年轻细胞。总的来说,新生神经元的增强兴奋性不会产生过度活跃,而是会平衡兴奋性输入突触的数量较少。最后,新生神经元中的稀疏编码已被证明对学习行为的神经发生依赖性改善至关重要。总之,来自细胞生理学和行为研究的综合证据表明了一种可以解释成年神经发生对大脑功能的有益影响的机制。