IBYME-CONICET, Laboratorio de Biologia del Comportamiento, Vuelta de Obligado 2490, Ciudad de Buenos Aires, Buenos Aires, Argentina.
Neuroscience. 2009 Nov 10;163(4):1031-8. doi: 10.1016/j.neuroscience.2009.07.037. Epub 2009 Jul 24.
Changes in transcription levels of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP) response element binding (CREB), Synapsin I, Ca(2+)/calmodulin-dependent protein kinase II (CamKII), activity-regulated cytoskeleton-associated protein (Arc), c-jun and c-fos have been associated to several learning paradigms in different brain areas. In this study, we measured mRNA expression in the hippocampus by real time (RT)-PCR mRNA levels of BDNF, CREB, Synapsin I, CamKII, Arc, c-jun and c-fos, during learning and operant conditioning task. Experimental groups were as follows: control (C, the animals never left the bioterium), when the animals reached 50-65% of the expected response (Incompletely Trained, IT), when animals reached 100% of the expected response with a latency time lower than 5 s (Trained, Tr), Box Control of Incompletely Trained (BCIT), animals spent the same time as the IT in the operant conditioning box and Box Control of Trained (BCTr) animals spent the same time as the Tr in the operant conditioning box. All rats were killed at the same time by cervical dislocation 15 min after training and hippocampi were removed and processed. We found increments of mRNA levels of most genes (BDNF, CREB, Synapsin I, Arc, c-jun and c-fos) in IT and Tr groups compared to their box controls, but increments in Tr were smaller compared with IT. These results describe a differential gene expression in the rat hippocampus when the animals are learning and when animals have already learned. Taking together the results presented herein with the known functions of these genes, we propose a link between changes in gene expression in the hippocampus and different degrees of cellular activation and plasticity during learning of an operant conditioning task.
脑源性神经营养因子（BDNF）、环磷酸腺苷（cAMP）反应元件结合（CREB）、突触素 I、钙/钙调蛋白依赖性蛋白激酶 II（CamKII）、活性调节细胞骨架相关蛋白（Arc）、c-jun 和 c-fos 的转录水平变化与不同脑区的几种学习范式有关。在这项研究中，我们通过实时（RT）-PCR 测量了海马体中的 mRNA 表达，测量了学习和操作性条件反射任务过程中 BDNF、CREB、突触素 I、CamKII、Arc、c-jun 和 c-fos 的 mRNA 水平。实验组如下：对照组（C，动物从未离开过生物实验室），当动物达到预期反应的 50-65%时（不完全训练，IT），当动物达到 100%的预期反应且潜伏期低于 5 秒时（训练，Tr），不完全训练的操作箱对照（BCIT），动物在操作性条件反射箱中花费与 IT 相同的时间，以及训练的操作箱对照（BCTr），动物在操作性条件反射箱中花费与 Tr 相同的时间。所有大鼠均在训练后 15 分钟通过颈椎脱位同时处死，取出海马体并进行处理。我们发现，与各自的箱控组相比，IT 和 Tr 组的大多数基因（BDNF、CREB、突触素 I、Arc、c-jun 和 c-fos）的 mRNA 水平都有所增加，但 Tr 组的增加幅度小于 IT 组。这些结果描述了大鼠海马体在学习和已经学习时基因表达的差异。将本文呈现的结果与这些基因的已知功能结合起来，我们提出了海马体基因表达变化与操作性条件反射任务学习过程中不同程度的细胞激活和可塑性之间的联系。
