The Wellcome Trust Centre for Human Genetics, The University of Oxford, Oxford, United Kingdom.
PLoS Genet. 2013;9(9):e1003718. doi: 10.1371/journal.pgen.1003718. Epub 2013 Sep 5.
The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.
成年神经发生在啮齿动物大脑中的功能仍不清楚。成年神经元的消融产生了关于情绪和认知障碍的相互矛盾的结果。一种假设是，海马体中的成年神经发生使空间模式分离，使动物能够区分相似的刺激。我们研究了在一种新型的大鼠神经发生消融的遗传模型中，海马体中的成年神经发生的空间模式分离和其他假定的海马体功能是否发生了改变。在表达胸苷激酶 (TK) 的大鼠中，启动子来自大鼠胶质纤维酸性蛋白 (GFAP)，用更昔洛韦治疗可使新神经元减少 98%。GFAP-TK 大鼠在放射状迷宫上的空间模式分离、水迷宫中的空间学习、上下文或线索恐惧条件反射方面与对照组没有显著差异。对所有已发表研究的荟萃分析发现，成年神经发生的消融对空间记忆、线索条件反射或焦虑的行为测量没有显著影响。在 5%（P = 0.04）的阈值下，对上下文冻结的影响显著，但在针对多次测试校正的阈值下则不显著。荟萃分析显示，海马体功能研究之间存在显著的异质性。这种异质性的来源尚不清楚，这对成年神经发生功能的研究构成了挑战。
