LTP-Related Gene Networks Figure 7. IPA network analysis at 5 h. The three highest scoring networks from LRG list are shown. Red, upregulated genes; green, downregulated genes. White open nodes, genes not present in LRG set but that interact with LRGs, as identified by the IPA Knowledge Base. A solid line denotes a direct functional interaction of the products of the two genes. A dotted line denotes an indirect interaction. An arrow indicates that a gene product ‘‘acts on’’ a target. *, Multiple affymetrix identifiers map to a single gene. doi:10.1371/journal.pone.0040538.g007 within 5 h-Network 3 (Figure 7C; Score 18). While regulation of microRNA was not directly assessed in this study using Affymetrix RAT 230 2.0 arrays, the prediction generated by the IPA software that microRNA form central hubs within our networks is of particular note as microRNA are proposed to be central regulators of functionally related genes [47]. This is mediated by binding to the 39untranslated region of target mRNAs, which results in translation repression and/or mRNA degradation. Interestingly, this process has been shown to occur in dendrites, and microRNA accordingly have also been proposed as key regulators of protein synthesis-dependent synaptic plasticity [48,49,50]. As MIR24-1 is linked to 5 genes that are upregulated in response to LTP, the prediction from this network analysis is that MIR24-1 is downregulated in response to LTP, thus allowing the PLoS ONE | www.plosone.org 8 July 2012 | Volume 7 | Issue 7 | e40538