Cuppini Riccardo, Bucherelli Corrado, Ambrogini Patrizia, Ciuffoli Stefano, Orsini Laura, Ferri Paola, Baldi Elisabetta
Institute of Physiological Sciences, University of Urbino Carlo Bo, Urbino, Italy.
Hippocampus. 2006;16(2):141-8. doi: 10.1002/hipo.20140.
New neuron production throughout adulthood in granule cell layer (GCL) of rat hippocampus is a well-known phenomenon. A role of new neurons in hippocampal learning has been proposed, but the question is still open. A reduction of neural precursor proliferation in GCL of 2-month-old rats to about 20%, induced by the cytostatic agent methylazoxymethanol, was found to cause impairment in trace conditioning, suggesting a role of immature neurons in this kind of hippocampus-dependent learning (Shors et al., Hippocampus 2002;12:578-584). Neurogenesis decreases with increasing age. In this study, neural precursor proliferation and newborn cell survival were evaluated in GCL of adult rats within a range of ages following development and preceding old age. In 5-month-old rats, neural precursor proliferation was reduced to 57% and newborn cell survival was reduced to 40% in comparison to rats of 2 months of age; in 12-month-old rats, the decrease was to 5 and 4%, respectively. Consistently, the density of immature neurons decreased to 41 and 13% in 5- and 12-month-old rats, respectively. The role of neurogenesis in trace fear conditioning was studied in this natural model of neurogenesis depression. No impairment in trace fear conditioning was found both in 5- and 12-month-old rats in comparison to 2-month-old rats, notwithstanding the decrease of neurogenesis that is marked in 12-month-old rats. This finding shows that a lower rate of neurogenesis is sufficient for learning in 12-month-old rats in comparison to young rats.
成年大鼠海马颗粒细胞层(GCL)在整个成年期持续产生新神经元是一个广为人知的现象。新神经元在海马体学习中的作用已被提出,但问题仍未解决。发现细胞抑制剂甲基偶氮甲醇可使2月龄大鼠GCL中的神经前体细胞增殖减少至约20%,这会导致痕迹条件反射受损,表明未成熟神经元在这种依赖海马体的学习中发挥作用(肖尔斯等人,《海马体》2002年;12:578 - 584)。神经发生随着年龄增长而减少。在本研究中,对成年大鼠发育后至老年前不同年龄段的GCL中的神经前体细胞增殖和新生细胞存活情况进行了评估。与2月龄大鼠相比,5月龄大鼠的神经前体细胞增殖减少至57%,新生细胞存活减少至40%;12月龄大鼠的这一比例分别降至5%和4%。同样,5月龄和12月龄大鼠中未成熟神经元的密度分别降至41%和13%。在这个神经发生抑制的自然模型中研究了神经发生在痕迹恐惧条件反射中的作用。与2月龄大鼠相比,5月龄和12月龄大鼠在痕迹恐惧条件反射中均未发现受损,尽管12月龄大鼠的神经发生明显减少。这一发现表明,与年轻大鼠相比,较低的神经发生率足以支持12月龄大鼠的学习。