Bicakci Ahmet Oguzhan, Tsai Pei-Ling, Kahl Evelyn, Mayer Dana, Fendt Markus
Institute for Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
Integrative Neuroscience Program, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany.
Pharmaceuticals (Basel). 2021 Jul 5;14(7):643. doi: 10.3390/ph14070643.
Cognitive flexibility refers to the ability to modify learned behavior in response to changes in the environment. In laboratory rodents, cognitive flexibility can be assessed in reversal learning, i.e., the change of contingencies, for example in T-maze discrimination learning. The present study investigated the role of the neuropeptide S (NPS) system in cognitive flexibility. In the first experiment, mice deficient of NPS receptors (NPSR) were tested in T-maze discrimination and reversal learning. In the second experiment, C57BL/6J mice were tested in the T-maze after nasal administration of NPS. Finally, the effect of nasal NPS on locomotor activity was evaluated. NPSR deficiency positively affected the acquisition of T-maze discrimination but had no effects on reversal learning. Nasal NPS administration facilitated reversal learning and supported an allocentric learning strategy without affecting acquisition of the task or locomotor activity. Taken together, the present data show that the NPS system is able to modulate both acquisition of T-maze discrimination and its reversal learning. However, NPSR deficiency only improved discrimination learning, while nasal NPS administration only improved reversal learning, i.e., cognitive flexibility. These effects, which at first glance appear to be contradictory, could be due to the different roles of the NPS system in the brain regions that are important for learning and cognitive flexibility.
认知灵活性是指根据环境变化改变习得行为的能力。在实验啮齿动物中，认知灵活性可在反转学习中进行评估，即改变意外情况，例如在T型迷宫辨别学习中。本研究调查了神经肽S（NPS）系统在认知灵活性中的作用。在第一个实验中，对缺乏NPS受体（NPSR）的小鼠进行T型迷宫辨别和反转学习测试。在第二个实验中，对C57BL/6J小鼠经鼻腔给予NPS后进行T型迷宫测试。最后，评估经鼻腔给予NPS对运动活动的影响。NPSR缺乏对T型迷宫辨别的习得有积极影响，但对反转学习没有影响。经鼻腔给予NPS促进了反转学习，并支持一种以自我为中心的学习策略，而不影响任务的习得或运动活动。综上所述，目前的数据表明，NPS系统能够调节T型迷宫辨别及其反转学习的习得。然而，NPSR缺乏仅改善了辨别学习，而经鼻腔给予NPS仅改善了反转学习，即认知灵活性。这些乍一看似乎相互矛盾的效应，可能是由于NPS系统在对学习和认知灵活性至关重要的脑区中发挥的不同作用所致。
