title: MicroRNAs, miR-23a-3p and miR-151-3p, Are Regulated in Dentate Gyrus Neuropil following Induction of Long-Term Potentiation In Vivo.
abstract: Translation of synaptic mRNA contributes to alterations in the proteome necessary to consolidate long-term potentiation (LTP), a model of memory processes. Yet, how this process is controlled is not fully resolved. MicroRNAs are non-coding RNAs that negatively regulate gene expression by suppressing translation or promoting mRNA degradation. As specific microRNAs are synaptically located, we hypothesized that they are ideally suited to couple synaptic activation, translational regulation, and LTP persistence. The aim of this study was to identify LTP-regulated microRNAs at or near synapses. Accordingly, LTP was induced unilaterally at perforant path-dentate gyrus synapses in awake adult Sprague-Dawley rats. Five hours later, dentate gyrus middle molecular layer neuropil, containing potentiated synapses, was laser-microdissected. MicroRNA expression profiling, using TaqMan Low Density MicroRNA Microarrays (n = 4), identified eight regulated microRNAs. Subsequent individual TaqMan assays confirmed upregulation of miR-23a-3p (1.30 ± 0.10; p = 0.015) and miR-151-3p (1.17 ± 0.19; p = 0.045) in a second cohort (n = 7). Interestingly, bioinformatic analysis indicated that miR-151-3p and miR-23a-3p regulate synaptic reorganisation and transcription, respectively. In summary, we have demonstrated for the first time that microRNAs are regulated in isolated neuropil following LTP induction in vivo, supporting the hypothesis that synaptic, LTP-responsive microRNAs contribute to LTP persistence via regulation of the synaptic proteome.
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.|The Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
authors.forename: Brigid
authors.initials: B
authors.lastname: Ryan
authors.affiliation: The Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.|Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Logan
authors.affiliation: The Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.|Department of Psychology, University of Otago, Dunedin, New Zealand.
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.affiliation: Department of Anatomy, University of Otago, Dunedin, New Zealand.|The Brain Health Research Centre, University of Otago, Dunedin, New Zealand.|Brain Research New Zealand, Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
authors.forename: Joanna M
authors.identifier: http://orcid.org/0000-0003-3936-2220
authors.initials: JM
authors.lastname: Williams
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism*; D005786:Gene Expression Regulation; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019581:Neuropil / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C000588814:MIRN151 microRNA, rat; C000590974:MIRN23a microRNA, rat