Drapeau Elodie, Montaron Marie-Françoise, Aguerre Sylvie, Abrous Djoher Nora
Institut National de la Santé et de la Recherche Médicale U862, Bordeaux Neuroscience Research Center, University of Bordeaux 2, Bordeaux, France.
J Neurosci. 2007 May 30;27(22):6037-44. doi: 10.1523/JNEUROSCI.1031-07.2007.
Aging is accompanied by an alteration of spatial memory, which has been related to an alteration in hippocampal plasticity. Within the dentate gyrus, new neurons are generated throughout the entire life of an individual. This neurogenesis seems to play a role in hippocampal-mediated learning and learning-induced changes in neurogenesis have been proposed to be involved in memory. However, in aged rats, little is known on the influence of learning on the early development of the adult-born neurons and on the possible involvement of learning-induced changes in neurogenesis in age-related memory deficits. To address this issue, we took advantage of the existence of spontaneous individual differences for performances observed in aged subjects in the water maze. In this task, learning can be divided into two phases, an early phase during which performances quickly improve, and a late phase during which asymptotic levels of performances are reached. We show that the influence of spatial learning on the survival of the newly born cells depends on their birth date and the memory abilities of the aged rats. In aged rats with preserved spatial memory, learning increases the survival of cells generated before learning whereas it decreases survival of cells produced during the early phase of learning. These results highlight the importance of learning-induced changes in adult-born cell survival in memory. Furthermore, they provide new insights on the possible neural mechanisms of aging of cognitive functions and show that an alteration to the steps leading to neurogenesis may be involved in the determination of individual memory abilities.
衰老伴随着空间记忆的改变,这与海马可塑性的改变有关。在齿状回中,新神经元在个体的整个生命过程中不断产生。这种神经发生似乎在海马介导的学习中发挥作用,并且有人提出学习诱导的神经发生变化与记忆有关。然而,在老年大鼠中,关于学习对成年新生神经元早期发育的影响以及学习诱导的神经发生变化是否可能参与与年龄相关的记忆缺陷,我们知之甚少。为了解决这个问题,我们利用了老年受试者在水迷宫中表现出的自发个体差异。在这个任务中,学习可以分为两个阶段,一个早期阶段,在此期间表现迅速提高,以及一个晚期阶段,在此期间达到表现的渐近水平。我们表明,空间学习对新生细胞存活的影响取决于它们的出生日期和老年大鼠的记忆能力。在空间记忆保留的老年大鼠中,学习增加了学习前产生的细胞的存活率,而降低了学习早期阶段产生的细胞的存活率。这些结果突出了学习诱导的成年新生细胞存活变化在记忆中的重要性。此外,它们为认知功能衰老的可能神经机制提供了新的见解,并表明导致神经发生的步骤的改变可能参与个体记忆能力的决定。