Function of microRNAs in long-term potentiation

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIMH	NEURO/BEHAV/SENSYS-29

* FARE Award Winner

Author

• Q Gu

Abstract

Long-lasting forms of synaptic plasticity, such as LTP, are believed to be important cellular mechanisms for learning and memory. Circumferential evidence suggests that microRNAs may regulate the protein synthesis-dependent late-phase synaptic plasticity. To test this hypothesis, first we used deep sequencing to analyze microRNA expression profiles following LTP induction, and selected miRNAs changed in LTP as candidate “LTP microRNAs”. Second we investigated the role of two candidate microRNAs, miR-26a and miR-384-5p, in LTP. Both of them are down-regulated undergoing LTP, and interestingly, both predicted to target to RSK3. We transduced cultured hippocampal slices with lentivirus expressing these two miRNAs and recorded LTP. The protein-synthesis dependent L-LTP was impaired remarkably. Likewise, RSK inhibitor also blocked L-LTP. Inhibition of L-LTP by miR-26a was abolished by transduction of RSK3 expressing lentivirus, suggesting that the effect of miR-26a on LTP is mediated by reduction of RSK3 expression. In addition, we find over-expression of miR-26a and miR-384-5p dramatically reduced spine changes in L-LTP. Taken together, our results indicate that microRNA expression change is an important mechanism for controlling protein synthesis to maintain the structural and functional changes in L-LTP; and that miR-26 and miR-384-5p are two miRNAs specifically regulate maintenance of L-LTP.

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