Figure 1. Expression profiling of miRNAs reveals 21 miRNAs that are induced in the hippocampus of adult rats 24 hr post-contextual fear conditioning.
(A) Schematic representation of contextual fear conditioning paradigm. Rats were trained to associate an aversive unconditioned stimulus (foot shock) with the environment (context). Freezing behavior was examined 24 hr after contextual fear conditioning training for a control group of rats (n = 4 for each group, naïve and trained), a subset of rats for which tissue was not harvested. Error bars indicate SEM. P value from pairwise unpaired t-test is indicated with asterisks, *p<0.05. (B) MiRNAs that displayed at least a 1.5-fold increase in expression between trained and naïve rats in three different experiments. (C) Network analysis using MetaCore (Thompson Reuters) identifies pathways involved in neuronal development, vesicle exocytosis and synaptic plasticity that are co-regulated by three or more of the fear induced miRNAs identified in panel B. P values were calculated for each canonical signaling pathway as compared to the number of occurrences from random sets of brain-expressed genes (see Materials and methods for a detailed description of brain-expressed gene lists). All 6 of the pathways are statistically significant compared to random sets of brain-expressed genes, ***p<0.0001. (D) MiR-153 and miR-9 are the top two miRNAs co-regulating targets involved in the vesicle exocytosis pathway. (E) Eight predicted targets from the vesicle exocytosis pathway that may be co-regulated by miR-153 and at least two other fear-induced miRNAs. The potential targeting fear-miRNAs are indicated above each target.
Figure 1—figure supplement 1. Identification of hippocampal fear-induced miRNAs.
Figure 1—figure supplement 2. Additional targets shared between miR-153 and other fear-induced miRNAs.
