Olariu Ana, Cleaver Kathryn M, Shore Lauren E, Brewer Michelle D, Cameron Heather A
Unit on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Hippocampus. 2005;15(6):750-62. doi: 10.1002/hipo.20097.
Granule cells born in the adult dentate gyrus undergo a 4-week developmental period characterized by high susceptibility to cell death. Two forms of hippocampus-dependent learning have been shown to rescue many of the new neurons during this critical period. Here, we show that a natural form of associative learning, social transmission of food preference (STFP), can either increase or decrease the survival of young granule cells in adult rats. Increased numbers of pyknotic as well as phospho-Akt-expressing BrdU-labeled cells were seen 1 day after STFP training, indicating that training rapidly induces both cell death and active suppression of cell death in different subsets. A single day of training for STFP increased the survival of 8-day-old BrdU-labeled cells when examined 1 week later. In contrast, 2 days of training decreased the survival of BrdU-labeled cells and the density of immature neurons, identified with crmp-4. This change from increased to decreased survival could not be accounted for by the ages of the cells. Instead, we propose that training may initially increase young granule cell survival, then, if continued, cause them to die. This complex regulation of cell death could potentially serve to maintain granule cells that are actively involved in memory consolidation, while rapidly using and discarding young granule cells whose training is complete to make space for new naïve neurons.
成体齿状回中生成的颗粒细胞会经历一个为期4周的发育期,其特征是对细胞死亡高度敏感。两种依赖海马体的学习形式已被证明能在这个关键时期挽救许多新生神经元。在此,我们表明一种自然形式的联想学习,即食物偏好的社会传递(STFP),可以增加或减少成年大鼠中年轻颗粒细胞的存活。在STFP训练后1天,可见到更多的固缩以及表达磷酸化Akt的BrdU标记细胞,这表明训练能在不同亚群中迅速诱导细胞死亡和对细胞死亡的主动抑制。当在1周后检查时,单日的STFP训练增加了8天大的BrdU标记细胞的存活。相反,2天的训练降低了BrdU标记细胞的存活以及用crmp - 4鉴定的未成熟神经元的密度。这种从存活增加到存活减少的变化不能用细胞的年龄来解释。相反,我们提出训练可能最初会增加年轻颗粒细胞的存活,然后,如果持续下去,则会导致它们死亡。这种对细胞死亡的复杂调节可能有助于维持积极参与记忆巩固的颗粒细胞,同时迅速利用并丢弃训练已完成的年轻颗粒细胞,以便为新的幼稚神经元腾出空间。