the timing of differentiation of adult hippocampal neurons is crucial for spatial memory成年人的海马神经元的分化时间对空间记忆是至关重要的.pdfVIP

PLoS BIOLOGY The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory 1[ 2,3[ 2,3[ 4[ ` 1 Stefano Farioli-Vecchioli , Daniele Saraulli , Marco Costanzi , Simone Pacioni , Irene Cina , Massimiliano Aceti2 1 4 2,3 1* , Laura Micheli , Alberto Bacci , Vincenzo Cestari , Felice Tirone 1 Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, Fondazione S. Lucia, Rome, Italy, 2 Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Rome, Italy, 3 LUMSA University, Faculty of Educational Science, Rome, Italy, 4 European Brain Research Institute, Rome, Italy Adult neurogenesis in the dentate gyrus plays a critical role in hippocampus-dependent spatial learning. It remains unknown, however, how new neurons become functionally integrated into spatial circuits and contribute to hippocampus-mediated forms of learning and memory. To investigate these issues, we used a mouse model in which the differentiation of adult-generated dentate gyrus neurons can be anticipated by conditionally expressing the pro- differentiative gene PC3 (Tis21/BTG2) in nestin-positive progenitor cells. In contrast to previous studies that affected the number of newly generated neurons, this strategy selectively changes their timing of differentiation. New, adult- generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation and significantly reduced dendritic arborization and spine density. Functionally, this gen