Laboratorio de Biología del Comportamiento, IBYME-CONICET, Ciudad de Buenos Aires, Buenos Aires, Argentina.
PLoS One. 2011 Feb 18;6(2):e14713. doi: 10.1371/journal.pone.0014713.
Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP) during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU) injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task) when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task) when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC) in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and neuronal maturation depending on the learning phase in the mPFC-HIPP circuit.
与学习和记忆相关的回路修饰涉及多个事件,包括成年期新生细胞的增加和去除。成年神经发生和神经胶质发生主要在自愿运动、丰富环境、空间学习和记忆任务的模型中描述;然而,它是否是不同学习模式(如奖励依赖任务)之间的共同机制尚不清楚。因此,我们评估了学习操作性条件反射任务期间内侧前额叶皮层(mPFC)和海马体(HIPP)中的细胞增殖、神经发生、神经胶质发生、存活和神经元成熟。这是通过使用细胞增殖的内源性标记物以及溴脱氧尿苷(BrdU)在学习的两个不同阶段的注射方案来完成的。学习操作性条件反射分为两个阶段:第一阶段是当动物被认为是不完全训练时(IT,正在学习任务的动物),当它们执行 50%到 65%的反应时;第二阶段是当动物被认为是完全训练时(Tr,完全学习任务的动物),当它们达到 100%的反应且潜伏期低于 5 秒时。我们发现学习操作性条件反射任务促进了 mPFC 和 HIPP 中两个学习阶段的细胞增殖。此外,结果表明,在两个阶段中,内侧前额叶皮层(mPFC)中的神经胶质发生都被诱导,然而,第一阶段促进了这些新生神经胶质细胞的存活。另一方面,仅在第一阶段观察到 HIPP 中新生未成熟神经元的数量增加,而在第二阶段观察到数量减少。最后,我们发现只有在第一阶段才诱导神经元成熟。这项研究首次表明,学习奖励依赖任务,如操作性条件反射,根据 mPFC-HIPP 回路中的学习阶段,促进神经发生、神经胶质发生、存活和神经元成熟。