Nestin Null Mice Show Improved Reversal Place Learning

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.