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microRNA Regulation of Synaptic Plasticity

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Abstract

microRNAs play an important role in regulating synaptic plasticity. For example, microRNAs target (and are targeted by) plasticity mediators such as CREB, MECP2, and FMRP. As well, specific microRNAs have been shown to be expressed within dendrites, where they regulate protein translation of targets mediating dendritic growth. Components of the RISC machinery have been implicated in long-term memory in Drosophila. Here, we review evidence from studies of adult mouse forebrain supporting a model wherein synaptic stimulation (above a threshold value) increases calcium within dendritic spines, activates calpain, and activates and releases dicer from the postsynaptic density. Dicer processes local pre-miRs into mature miRNAs that are incorporated into RISC complexes within or near the dendritic spine, and that bind available target mRNAs in the vicinity. These may repress protein translation under resting conditions, yet permit a phasic burst of translation to occur transiently following subsequent synaptic activity. Loaded RISC complexes that are not bound to local mRNAs may serve to bind and trap mRNAs that are being transported down dendrites. Thus, locally formed microRNAs may mark the location of previously activated synapses and perform a type of synaptic tagging and capture.

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Acknowledgments

We are grateful to Drs. John Larson, Yogesh Dwivedi, and Vetle Torvik for their expert collaborations. Our research was supported by NIH grants DA15450, MH81099, DC 05793, and LM07292 and by the Stanley Medical Research Institute. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of NIH.

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  1. Department of Psychiatry and UIC Psychiatric Institute, MC912, University of Illinois at Chicago, 1601 W. Taylor Street, Chicago, IL, 60612, USA

    Neil R. Smalheiser & Giovanni Lugli

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  1. Neil R. Smalheiser
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  2. Giovanni Lugli
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Correspondence to Neil R. Smalheiser.

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Smalheiser, N.R., Lugli, G. microRNA Regulation of Synaptic Plasticity. Neuromol Med 11, 133–140 (2009). https://doi.org/10.1007/s12017-009-8065-2

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