Center for Neuroscience
Department of Psychiatry and Behavioral Neuroscience.
eNeuro. 2020 May 20;7(3). doi: 10.1523/ENEURO.0030-20.2020. Print 2020 May/Jun.
Mouse hippocampus retains the capacity for neurogenesis throughout lifetime, but such plasticity decreases with age. Adult hippocampal neurogenesis (AHN) involves the birth, maturation, and synaptic integration of newborn granule cells (GCs) into preexisting hippocampal circuitry. While functional integration onto adult-born GCs has been extensively studied, maturation of efferent projections onto CA3 pyramidal cells is less understood, particularly in aged brain. Here, using combined light and reconstructive electron microscopy (EM), we describe the maturation of mossy fiber bouton (MFB) connectivity with CA3 pyramidal cells in young adult and aged mouse brain. We found mature synaptic contacts of newborn GCs were formed in both young and aged brains. However, the dynamics of their spatiotemporal development and the cellular process by which these cells functionally integrated over time were different. In young brain newborn GCs either formed independent nascent MFB synaptic contacts or replaced preexisting MFBs, but these contacts were pruned over time to a mature state. In aged brain only replacement of preexisting MFBs was observed and new contacts were without evidence of pruning. These data illustrate that functional synaptic integration of AHN occurs in young adult and aged brain, but with distinct dynamics. They suggest elimination of preexisting connectivity is required for the integration of adult-born GCs in aged brain.
小鼠海马体在整个生命周期中都保持着神经发生的能力，但这种可塑性随着年龄的增长而下降。成年海马神经发生（AHN）涉及新生颗粒细胞（GCs）的产生、成熟和突触整合到海马体的预先存在的回路中。虽然对成年新生 GC 的功能整合进行了广泛的研究，但对 CA3 锥体神经元上的传出投射的成熟了解较少，特别是在老年大脑中。在这里，我们使用结合了光和重建电子显微镜（EM），描述了在年轻成年和老年小鼠大脑中，苔藓纤维末梢（MFB）与 CA3 锥体神经元的连接的成熟过程。我们发现，新生 GC 的成熟突触接触在年轻和老年大脑中均有形成。然而，它们的时空发育动态以及这些细胞随时间功能整合的细胞过程是不同的。在年轻的大脑中，新生 GC 要么形成独立的新生 MFB 突触接触，要么取代现有的 MFB，但这些接触会随着时间的推移被修剪到成熟状态。在老年大脑中，只观察到对现有 MFB 的取代，而新的接触没有修剪的证据。这些数据表明，AHN 的功能突触整合发生在年轻成年和老年大脑中，但具有不同的动态。它们表明，在老年大脑中，需要消除现有的连接才能实现成年新生 GC 的整合。
