Trinchero Mariela F, Herrero Magalí, Monzón-Salinas M Cristina, Schinder Alejandro F
Laboratorio de Plasticidad Neuronal, Fundación Instituto Leloir, Buenos Aires, Argentina.
Front Neurosci. 2019 Jul 17;13:739. doi: 10.3389/fnins.2019.00739. eCollection 2019.
Synaptic modification in cortical structures underlies the acquisition of novel information that results in learning and memory formation. In the adult dentate gyrus, circuit remodeling is boosted by the generation of new granule cells (GCs) that contribute to specific aspects of memory encoding. These forms of plasticity decrease in the aging brain, where both the rate of adult neurogenesis and the speed of morphological maturation of newly generated neurons decline. In the young-adult brain, a brief novel experience accelerates the integration of new neurons. The extent to which such degree of plasticity is preserved in the aging hippocampus remains unclear. In this work, we characterized the time course of functional integration of adult-born GCs in middle-aged mice. We performed whole-cell recordings in developing GCs from Ascl1;CAG mice and found a late onset of functional excitatory synaptogenesis, which occurred at 4 weeks (vs. 2 weeks in young-adult mice). Overall mature excitability and maximal glutamatergic connectivity were achieved at 10 weeks. In contrast, large mossy fiber boutons (MFBs) in CA3 displayed mature morphological features including filopodial extensions at 4 weeks, suggesting that efferent connectivity develops faster than afference. Notably, new GCs from mice exposed to enriched environment for 7 days showed an advanced degree of maturity at 3 weeks, revealed by the high frequency of excitatory postsynaptic responses, complex dendritic trees, and large size of MFBs with filopodial extensions. These findings demonstrate that adult-born neurons act as sensors that transduce behavioral stimuli into major network remodeling in the aging brain.
皮质结构中的突触修饰是获取导致学习和记忆形成的新信息的基础。在成年齿状回中，新颗粒细胞（GCs）的产生促进了回路重塑，这些新颗粒细胞有助于记忆编码的特定方面。在衰老大脑中，这些可塑性形式会降低，其中成年神经发生的速率和新生成神经元的形态成熟速度都会下降。在年轻成年大脑中，短暂的新体验会加速新神经元的整合。在衰老海马体中这种可塑性程度保留的程度尚不清楚。在这项工作中，我们描述了中年小鼠中成年出生的GCs功能整合的时间进程。我们对Ascl1;CAG小鼠发育中的GCs进行了全细胞记录，并发现功能性兴奋性突触发生的起始较晚，发生在4周时（而年轻成年小鼠为2周）。总体成熟兴奋性和最大谷氨酸能连接性在10周时实现。相比之下，CA3中的大型苔藓纤维终扣（MFBs）在4周时显示出成熟的形态特征，包括丝状伪足延伸，这表明传出连接的发育比传入连接更快。值得注意的是，暴露于丰富环境7天的小鼠的新GCs在3周时显示出更高的成熟度，这通过兴奋性突触后反应的高频、复杂的树突状树以及带有丝状伪足延伸的大型MFBs得以揭示。这些发现表明，成年出生的神经元充当传感器，将行为刺激转化为衰老大脑中的主要网络重塑。
