selective survival and maturation of adult-born dentate granule cells expressing the immediate early gene arcarg3.1选择性的生存和成熟adult-born齿状颗粒细胞表达立即早期基因arcarg3.1.pdfVIP

Selective Survival and Maturation of Adult-Born Dentate Granule Cells Expressing the Immediate Early Gene Arc/ Arg3.1 Sjoukje D. Kuipers, Adrian Tiron, Jonathan Soule, Elhoucine Messaoudi, Andrea Trentani, Clive R. Bramham* Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Bergen, Norway Abstract Progenitor cells in the adult dentate gyrus provide a constant supply of neuronal precursors, yet only a small fraction of these cells survive and develop into mature dentate granule cells (DGCs). A major challenge of current research is thus to understand the stringent selection process that governs the maturation and functional integration of adult-born DGCs. In mature DGCs, high-frequency stimulation (HFS) of the perforant path input elicits robust expression of the immediate early gene Arc/Arg3.1, trafficking of its mRNA to dendrites, and local synthesis of the protein necessary for consolidation of long- term potentiation (LTP). Given the synaptic commitment inherent in LTP consolidation, we considered that HFS-evoked expression of Arc could be used to timemap the functional integration of newborn DGCs. Dividing cells were birthmarked by BrdU-labeling at 1, 7, 14, 21, or 28 days prior to induction of LTP and expression of Arc was examined by confocal microscopy. Contrary to expectation, LTP did not induce Arc expression in newborn cells at any age, suggesting they might be refractory to synaptically-evoked Arc expression for at least one month. Importantly, however, spontaneous expression of Arc was detected in BrdU-labeled cells and strongly associated with the survival and maturation of NeuN-positive DGCs. Moreover, Arc expression at the earliest ages (1 and 7 days), clearly precedes the formation of glutamatergic synapses on new neurons. These results suggest an unexpected early role for Arc in adult-born