temporal profiling of gene networks associated with the late phase of long-term potentiation in vivo时序分析的基因网络与体内长期电位化的后期阶段.pdfVIP

Temporal Profiling of Gene Networks Associated with the Late Phase of Long-Term Potentiation In Vivo Margaret M. Ryan1,2,3, Brigid Ryan1,2, Madeleine Kyrke-Smith1,2, Barbara Logan1,4, Warren P. Tate1,3, Wickliffe C. Abraham1,4, Joanna M. Williams1,2* 1 Brain Health Research Centre, University of Otago, Dunedin, New Zealand, 2 Department of Anatomy, Otago School of Medical Sciences, Dunedin, New Zealand, 3 Department of Biochemistry, Otago School of Medical Sciences, Dunedin, New Zealand, 4 Department of Psychology, University of Otago, Dunedin, New Zealand Abstract Long-term potentiation (LTP) is widely accepted as a cellular mechanism underlying memory processes. It is well established that LTP persistence is strongly dependent on activation of constitutive and inducible transcription factors, but there is limited information regarding the downstream gene networks and controlling elements that coalesce to stabilise LTP. To identify these gene networks, we used Affymetrix RAT230.2 microarrays to detect genes regulated 5 h and 24 h (n = 5) after LTP induction at perforant path synapses in the dentate gyrus of awake adult rats. The functional relationships of the differentially expressed genes were examined using DAVID and Ingenuity Pathway Analysis, and compared with our previous data derived 20 min post-LTP induction in vivo. This analysis showed that LTP-related genes are predominantly upregulated at 5 h but that there is pronounced downregulation of gene expression at 24 h after LTP induction. Analysis of the structure of the networks and canonical pathways predicted a regulation of calcium dynamics via G-protein coupled receptors, dendritogenesis and neurogenesis at the 5 h time-point. By 24 h neurotrophin-NFKB driven pathways of neuronal growth were identified. The temporal shi