Rapidly Induced Gene Networks Following Induction of Long-Term Potentiation at Perforant Path Synapses In Vivo

The canonical view of the maintenance of long-term potentiation (LTP), a widely accepted experimental model for memory processes, is that new gene transcription contributes to its consolidation; however, the gene networks involved are unknown. To address this issue, we have used high-density Rat 230.2 Affymetrix arrays to establish a set of genes induced 20-min post-LTP, and using Ingenuity Pathway network analysis tools we have investigated how these early responding genes are interrelated. This analysis identified LTP-induced regulatory networks in which the transcription factors (TFs) nuclear factor-KB and serum response factor, which, to date, have not been widely recognized as coordinating the early gene response, play a key role alongside the more well-known TFs cyclic AMP response element-binding protein, and early growth response 1. Analysis of gene-regulatory promoter sites and chromosomal locations of the genes within the data-set reinforced the importance of these molecules in the early gene response and predicted that the coordinated action might arise from gene clustering on particular chromosomes. We have also identified a transcription-based response that affects mitogen-activated protein kinase signaling pathways and protein synthesis during the stabilization of the LTP response. Furthermore, evidence from biological function, networks, and regulatory analyses showed convergence on genes related to development, proliferation, and neurogenesis, suggesting that these functions are regulated early following LTP induction. This raises the interesting possibility that LTP-related gene expression plays a role in both synaptic reorganization and neurogenesis. (C) 2010 Wiley-Liss, Inc.