Role of neurotransmitters and environmental enrichment in the critical period of brain development

哺乳动物海马结构的齿状回（DG）在整个成年期产生新的神经元。几个实验状态和调节神经发生的因素已被确定在成人DG。例如，暴露于丰富的环境中可以增强DG的神经发生，并改善海马依赖的空间学习。此外，已知血清素影响成人神经发生以及学习和记忆。然而，在发育期间长期缺乏5-羟色胺对神经发生的影响尚未研究。因此，我们研究了长期5-羟色胺缺乏对环境丰富诱导的神经发生和空间记忆表现的影响。如前所述，环境富集显著增加DG中的新神经元。然而，在标准和环境丰富housings. intracisternergic神经毒素，5，7-二羟色胺（5，7-DHT），出生后第3天的成年大鼠的空间学习测试没有改善明显降低5-羟色胺含量在成年海马没有再生。在丰富的环境中居住的大鼠海马中的5-羟色胺的实验耗尽对空间记忆性能没有影响，但在DG中溴脱氧尿苷（BrdU）标记的新细胞的数量显着减少。这些发现表明，环境丰富刺激的新产生的细胞对于改善依赖于校园的学习并不重要。此外，在5，7-DHT注射大鼠DG中BrdU标记细胞的数量在BrdU注射后1天和4周之间没有差异。这些数据表明，新产生的DG细胞的生存保持相对恒定的长期血清素耗竭。

ABSTRACTThe dentate gyrus(DG) of the hippocampal formation produces new neurons throughout adulthood in mammalian species. Several experimental statuses and factors regulating neurogenesis have been identified in the adult DG. For example, exposure to an enriched environment enhances neurogenesis in the DG and improves hippocampus-dependent spatial learning. Furthermore, serotonin is known to influence adult neurogenesis, and learning and memory. However, the effects of long-lasting depletion of serotonin over the developing period on the neurogenesis have not been investigated. Thus, we examined the influence of long-lasting serotonin depletion on the environmental enrichment-induced neurogenesis and spatial memory performance. As reported previously, environmental enrichment significantly increased new neurons in the DG. However, there was no improvement of spatial learning test in adult rats in standard and in environmental enrichment housings.Intracisternal administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), on postnatal day 3 apparently reduced serotonin content in the adult hippocampus without regeneration. This experimental depletion of serotonin in the hippocampus of rats housed in an enriched environment had no effect on spatial memory performance, but produced significant decreases in the number of bromodeoxyuridine (BrdU)-labeled new cells in the DG. These findings indicate that newly generated cells stimulated by environmental enrichment are not critical for improvements in hippocampus-dependent learning. Furthermore, numbers of BrdU-labeled cells in the DG of 5,7-DHT-injected rats did not differ between 1 day and 4 weeks after BrdU injection. These data suggest that survival of newly generated DG cells remains relatively constant under long-lasting serotonin depletion.