Long non-coding RNAs in formation of memory through long-term potentiation

Long-term potentiation (LTP) is a process of strengthening of signals across the synaptic cleft, and the process is believed to be involved in the formation of long-term memory. The protein-coding mechanisms of this phenomenon have been widely studied, however, the involvement of non-coding elements in the formation of increased synaptic connectivity has hitherto not been reported. Long noncoding RNAs have been shown to exert a wide selection of biological functions in the cell, and they are expressed in a cell specific manner.
To explore the role of ncRNA in LTP, we stimulated the dentate gyrus region in the right brain hippocampus in four anesthetised male Sprague-Dawley rats with a high frequency stimulation protocol widely used to induce LTP. RNA was extracted two hours after stimulation from the dentate gyrus, and total RNA sequencing was conducted on a HiSeq 2000. The left, unstimulated, dentate gyrus was used as transcriptional control.
In accordance with previous studies, various protein-coding genes known to be involved in neurogenesis and LTP were shown to be differentially expressed between the HFS stimulated side and control. Novel noncoding transcripts expressed in cis to known neuroplasticity genes exhibited elevated expression in stimulated samples. Moreover, miRNA not previously affiliated with neurogenesis was found to have an upregulated expression pattern after stimulation. Functional studies will be pursued to characterise the molecular mechanisms of these noncoding transcripts.
These data suggests novel evidence that noncoding RNAs function in memory formation and synaptic plasticity.
Authors: Jesper L. V. Mååg, Karin Wibrand, Debabrata Panja, Clive R. Bramham & Marcel Dinger

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