Mazzitelli-Fuentes Laura S, Román Fernanda R, Castillo Elías Julio R, Deleglise Emilia B, Mongiat Lucas A
Departamento de Física Médica, Centro Atómico Bariloche, Comisión Nacional de Energía Atómica, San Carlos de Bariloche, Argentina.
Consejo Nacional de Investigaciones Científicas y, Técnicas, Argentina.
Front Cell Dev Biol. 2022 May 11;10:840964. doi: 10.3389/fcell.2022.840964. eCollection 2022.
Adult neurogenesis could be considered as a homeostatic mechanism that accompanies the continuous growth of teleost fish. As an alternative but not excluding hypothesis, adult neurogenesis would provide a form of plasticity necessary to adapt the brain to environmental challenges. The zebrafish pallium is a brain structure involved in the processing of various cognitive functions and exhibits extended neurogenic niches throughout the periventricular zone. The involvement of neuronal addition as a learning-related plastic mechanism has not been explored in this model, yet. In this work, we trained adult zebrafish in a spatial behavioral paradigm and evaluated the neurogenic dynamics in different pallial niches. We found that adult zebrafish improved their performance in a cue-guided rhomboid maze throughout five daily sessions, being the fish able to relearn the task after a rule change. This cognitive activity increased cell proliferation exclusively in two pallial regions: the caudal lateral pallium (cLP) and the rostral medial pallium (rMP). To assessed whether learning impinges on pallial adult neurogenesis, mitotic cells were labeled by BrdU administration, and then fish were trained at different periods of adult-born neuron maturation. Our results indicate that adult-born neurons are being produced on demand in rMP and cLP during the learning process, but with distinct critical periods among these regions. Next, we evaluated the time course of adult neurogenesis by pulse and chase experiments. We found that labeled cells decreased between 4 and 32 dpl in both learning-sensitive regions, whereas a fraction of them continues proliferating over time. By modeling the population dynamics of neural stem cells (NSC), we propose that learning increases adult neurogenesis by two mechanisms: driving a chained proliferation of labeled NSC and rescuing newborn neurons from death. Our findings highlight adult neurogenesis as a conserved source of brain plasticity and shed light on a rostro-caudal specialization of pallial neurogenic niches in adult zebrafish.
成体神经发生可被视为一种伴随硬骨鱼持续生长的稳态机制。作为一种替代但不排除的假说,成体神经发生将提供一种可塑性形式,这对于使大脑适应环境挑战是必要的。斑马鱼大脑皮层是一种参与各种认知功能处理的脑结构,并且在整个脑室周围区域呈现出广泛的神经发生微环境。然而,在这个模型中,尚未探索神经元添加作为一种与学习相关的可塑性机制的作用。在这项工作中,我们在空间行为范式中训练成年斑马鱼,并评估不同大脑皮层微环境中的神经发生动态。我们发现成年斑马鱼在五个每日训练环节中,在提示引导的菱形迷宫中提高了它们的表现,并且在规则改变后能够重新学习任务。这种认知活动仅在两个大脑皮层区域增加了细胞增殖:尾侧外侧大脑皮层(cLP)和吻侧内侧大脑皮层(rMP)。为了评估学习是否影响大脑皮层的成体神经发生,通过给予溴脱氧尿苷(BrdU)标记有丝分裂细胞,然后在成年新生神经元成熟的不同时期对鱼进行训练。我们的结果表明,在学习过程中,成年新生神经元在rMP和cLP中按需产生,但这些区域之间有不同的关键期。接下来,我们通过脉冲和追踪实验评估成体神经发生的时间进程。我们发现在两个对学习敏感的区域中,标记细胞在移植后4至32天减少,而其中一部分细胞随着时间的推移继续增殖。通过对神经干细胞(NSC)的群体动态进行建模,我们提出学习通过两种机制增加成体神经发生:驱动标记的NSC的链式增殖以及挽救新生神经元免于死亡。我们的发现突出了成体神经发生作为大脑可塑性的保守来源,并揭示了成年斑马鱼大脑皮层神经发生微环境的前后轴特化。