The intermediate filament protein nestin is expressed by neural stem cells, but also by some astrocytes in the neurogenic niche of the hippocampus in the adult rodent brain. We recently reported that nestin-deficient (Nes^−/−) mice showed increased adult hippocampal neurogenesis, reduced Notch signaling from Nes^−/− astrocytes to the neural stem cells, and impaired long-term memory. Here we assessed learning and memory of Nes^−/− mice in a home cage set up using the IntelliCage system, in which the mice learn in which cage corner a nose poke earns access to drinking water. Nes^−/− and wildtype mice showed comparable place learning assessed as the incorrect corner visit ratio and the incorrect nose poke ratio. However, during reversal place learning, a more challenging task, Nes^−/− mice, compared to wildtype mice, showed improved learning over time demonstrated by the incorrect visit ratio and improved memory extinction over time assessed as nose pokes per visit to the previous drinking corner. In addition, Nes^−/− mice showed increased explorative activity as judged by the increased total numbers of corner visits and nose pokes. We conclude that Nes^−/− mice exhibit improved reversal place learning and memory extinction, a finding which together with the previous results supports the concept of the dual role of hippocampal neurogenesis in cognitive functions.

中间丝蛋白巢蛋白由神经干细胞表达，也由成年啮齿动物脑海马神经源性利基中的一些星形胶质细胞表达。我们最近报道，巢蛋白缺陷（Nes ^-/-）小鼠表现出成年海马神经发生增加，从Nes ^-/-星形胶质细胞到神经干细胞的Notch信号减少，并且损害了长期记忆。在这里，我们评估了使用IntelliCage系统设置的家用笼子中Nes ^-/-小鼠的学习和记忆能力，在该笼子中，小鼠学习了鼻子戳在哪个笼子角上获得饮用水。Nes ^-/-野生型小鼠表现出可比的位置学习，评估为不正确的拐角访问率和不正确的鼻子戳率。然而，在逆向学习中，与野生型小鼠相比，Nes ^-/-小鼠具有更大的挑战性，表现为随着时间的推移学习改善，这归因于不正确的访视率，并且随着时间的推移，记忆消退随着时间的推移而改善，这是每次饮酒前每次访视的鼻子戳角。另外，Nes ^-/-小鼠表现出增加的探索性活动，这一点可以通过转角访视和鼻子戳的总数增加来判断。我们得出结论，Nes ^-/- 小鼠表现出改善的逆向学习和记忆消退，这一发现与以前的结果一起支持了海马神经发生在认知功能中的双重作用的概念。