Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Behav Brain Res. 2012 Feb 14;227(2):497-507. doi: 10.1016/j.bbr.2011.10.009. Epub 2011 Oct 18.
Adult hippocampal neurogenesis is one of the most robust forms of synaptic plasticity in the nervous system and occurs throughout life. However, the rate of neurogenesis declines dramatically with age. Older animals have significantly less neural progenitor cell proliferation, neuronal differentiation, and newborn neuron survival compared to younger animals. Intrinsic properties of neural progenitor cells, such as gene transcription and telomerase activity, change with age, which may contribute to the observed decline in neurogenesis. In addition, age-related changes in the local cells of the neurogenic niche may no longer provide neural progenitor cells with the cell-cell contact and soluble cues necessary for hippocampal neurogenesis. Astrocytes, microglia, and endothelial cells undergo changes in morphology and signaling properties with age, altering the foundation of the neurogenic niche. While most studies indicate a correlation between decreased hippocampal neurogenesis and impaired performance in hippocampus-dependent cognitive tasks in aged mice, a few have demonstrated that young and aged mice are equivalent in their cognitive ability. Here, we summarize the different behavioral paradigms to test hippocampus-dependent cognition and the need to develop neurogenesis-dependent tasks.
成人海马神经发生是神经系统中最强的突触可塑性形式之一，并且发生在整个生命过程中。然而，神经发生的速度随着年龄的增长而显著下降。与年轻动物相比，老年动物的神经祖细胞增殖、神经元分化和新生神经元存活显著减少。神经祖细胞的内在特性，如基因转录和端粒酶活性，随年龄而变化，这可能导致观察到的神经发生下降。此外，神经发生龛位的与年龄相关的局部细胞变化可能不再为神经祖细胞提供海马神经发生所必需的细胞间接触和可溶性线索。星形胶质细胞、小胶质细胞和内皮细胞随着年龄的增长而在形态和信号转导特性上发生变化，改变了神经发生龛位的基础。虽然大多数研究表明，在老年小鼠中，海马神经发生减少与海马依赖认知任务的表现受损之间存在相关性，但也有一些研究表明，年轻和老年小鼠在认知能力方面是等效的。在这里，我们总结了不同的行为范式来测试海马依赖的认知，以及开发依赖于神经发生的任务的必要性。
