Stavroulaki Vasiliki, Ioakeimidis Vasileios, Konstantoudaki Xanthippi, Sidiropoulou Kyriaki
Faculty of Medicine, University of Crete, Heraklion, Greece.
Department of Biology, University of Crete, Heraklion, Greece.
J Neurosci Res. 2021 Jul;99(7):1802-1814. doi: 10.1002/jnr.24833. Epub 2021 Mar 19.
Working memory (WM) is the ability to hold on-line and manipulate information. The prefrontal cortex (PFC) is a key brain region involved in WM, while the hippocampus is also involved, particularly, in spatial WM. Although several studies have investigated the neuronal substrates of WM in trained animals, the effects and the mechanisms underlying learning WM tasks have not been explored. In our study, we investigated the effects of learning WM tasks in mice on the function of PFC and hippocampus, by training mice in the delayed alternation task for 9 days (adaptive group). This group was compared to naïve mice (which stayed in their homecage) and mice trained in the alternation procedure only (non-adaptive). Following training, a cohort of mice (Experiment A) was tested in the left-right discrimination task and the reversal learning task, while another cohort (Experiment B) was tested in the attention set-shifting task (AST). The adaptive group performed significantly better in the reversal learning task (Experiment A) and AST (Experiment B), compared to non-adaptive and naïve groups. At the end of the behavioral experiments in Experiment A, field excitatory post-synaptic potential (fEPSP) recordings were performed in PFC and hippocampal brain slices. The adaptive group had enhanced the long-term potentiation (LTP) in the PFC, compared to the other groups. In the hippocampus, both the adaptive and the non-adaptive groups exhibited increased fEPSP compared to the naïve group, but no differences in LTP. In Experiment B, the dendritic spine density was measured, which, in the PFC, was found increased in the adaptive group, compared to the non-adaptive and naïve groups. In the hippocampus, there was an increase in mature dendritic spine density in the adaptive group, compared to the other two groups. Our results indicate a role for LTP and dendritic spine density in learning WM tasks.
工作记忆（WM）是一种在线保存和处理信息的能力。前额叶皮质（PFC）是参与工作记忆的关键脑区，而海马体也参与其中，尤其是在空间工作记忆方面。尽管有多项研究调查了训练动物中工作记忆的神经元基础，但学习工作记忆任务的影响及潜在机制尚未得到探索。在我们的研究中，我们通过对小鼠进行9天的延迟交替任务训练（适应组），研究了小鼠学习工作记忆任务对PFC和海马体功能的影响。将该组与未训练的小鼠（留在其笼舍中）和仅在交替程序中训练的小鼠（非适应组）进行比较。训练后，一组小鼠（实验A）接受左右辨别任务和逆向学习任务测试，而另一组（实验B）接受注意力转换任务（AST）测试。与非适应组和未训练组相比，适应组在逆向学习任务（实验A）和AST（实验B）中的表现明显更好。在实验A的行为实验结束时，在PFC和海马脑片中进行了场兴奋性突触后电位（fEPSP）记录。与其他组相比，适应组增强了PFC中的长时程增强（LTP）。在海马体中，与未训练组相比，适应组和非适应组的fEPSP均增加，但LTP无差异。在实验B中，测量了树突棘密度，结果发现，与非适应组和未训练组相比，适应组PFC中的树突棘密度增加。与其他两组相比，适应组海马体中成熟树突棘密度增加。我们的结果表明LTP和树突棘密度在学习工作记忆任务中发挥作用。
