Olfactory discrimination training up-regulates and reorganizes expression of microRNAs in adult mouse hippocampus

Neil R. Smalheiser, Giovanni Lugli, Angela L. Lenon, John M. Davis, Vetle I. Torvik, John Larson

Research output: Contribution to journalArticle

Abstract

Adult male mice (strain C57Bl/6J) were trained to execute nose-poke responses for water reinforcement; then they were randomly assigned to either of two groups: olfactory discrimination training (exposed to two odours with reward contingent upon correctly responding to one odour) or pseudo-training (exposed to two odours with reward not contingent upon response). These were run in yoked fashion and killed when the discrimination-trained mouse reached a learning criterion of 70% correct responses in 20 trials, occurring after three sessions (a total of ∼40 min of training). The hippocampus was dissected bilaterally from each mouse (N=57 in each group) and profiling of 585 miRNAs (microRNAs) was carried out using multiplex RT-PCR (reverse transcription-PCR) plates. A significant global up-regulation of miRNA expression was observed in the discrimination training versus pseudo-training comparison; when tested individually, 29 miRNAs achieved significance at P=50.05. miR-10a showed a 2.7-fold increase with training, and is predicted to target several learning-related mRNAs including BDNF (brain-derived neurotrophic factor), CAMK2b (calcium/calmodulin-dependent protein kinase IIβ), CREB1 (cAMP-response-element-binding protein 1) and ELAVL2 [ELAV (embryonic lethal, abnormal vision, Drosophila)-like; Hu B]. Analysis of miRNA pairwise correlations revealed the existence of several miRNA co-expression modules that were specific to the training group. These in vivo results indicate that significant, dynamic and co-ordinated changes in miRNA expression accompany early stages of learning.

Original languageEnglish (US)
Article numbere00028
Pages (from-to)39-48
Number of pages10
JournalASN Neuro
Volume2
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Dicer
  • Learning
  • MicroRNA
  • Olfactory discrimination
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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