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Sci Rep. 2018 Mar 2;8(1):3950. doi: 10.1038/s41598-018-22278-w.

A CREB2-targeting microRNA is required for long-term memory after single-trial learning.

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Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, BN1 9QG, UK.
RDM Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Clifton, BS8 1UB, UK.
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, BN1 9QG, UK.
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia.


Although single-trial induced long-term memories (LTM) have been of major interest in neuroscience, how LTM can form after a single episode of learning remains largely unknown. We hypothesized that the removal of molecular inhibitory constraints by microRNAs (miRNAs) plays an important role in this process. To test this hypothesis, first we constructed small non-coding RNA (sncRNA) cDNA libraries from the CNS of Lymnaea stagnalis subjected to a single conditioning trial. Then, by next generation sequencing of these libraries, we identified a specific pool of miRNAs regulated by training. Of these miRNAs, we focussed on Lym-miR-137 whose seed region shows perfect complementarity to a target sequence in the 3' UTR of the mRNA for CREB2, a well-known memory repressor. We found that Lym-miR-137 was transiently up-regulated 1 h after single-trial conditioning, preceding a down-regulation of Lym-CREB2 mRNA. Furthermore, we discovered that Lym-miR-137 is co-expressed with Lym-CREB2 mRNA in an identified neuron with an established role in LTM. Finally, using an in vivo loss-of-function approach we demonstrated that Lym-miR-137 is required for single-trial induced LTM.

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